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.

Traditional gas sensing systems are facing efficiency challenges due to physically separated von Neumann architectures, making the construction of in-sensor computing neuromorphic olfactory systems urgently needed for low-power and low-latency scenarios. In this study, a reconfigurable neuromorphic heterostructure memristor based on MXene@SnS₂@PANI and an in-sensor computing olfactory system were proposed. Notably, the reconfigurable neuromorphic olfactory electronics differ fundamentally from conventional sensors. Specifically, the memristor’s circuit architecture supports both synaptic and neuronal computational functions, enabling reconfigurable responses to both electrical and gas stimuli within a single device, which substantially minimizes circuit complexity. Through modulation of the energy band under both gas and electrical signals, the device achieves reconfigurable neuromorphic computing features supporting both volatile and nonvolatile conductance updates. Under electrical stimulation, it demonstrates integrate-and-fire neuronal dynamics for gas flow recognition via a spiking neural network. Under gas exposure, neuromorphic synaptic behaviors are realized, enabling gas concentration identification through reservoir computing. The system has been successfully implemented for real-time hazardous gas monitoring and automated ventilation control, paving the way for next-generation neuromorphic intelligent sensing systems.

While sleep disorders are a known correlate of social memory deficits, the underlying neurocircuitry and molecular mechanisms remain poorly understood. Using an oxytocin (OXT)-specific sensor imaging approach, we discovered that chronic sleep deprivation (SD) reduced OXT neuropeptide release in the hippocampal CA2 and prelimbic cortex (PrL), thereby disrupting social memory encoding and retrieval processes, respectively. Using fiber photometry recordings and in vitro electrophysiology, we identified the activity of the predominantly OXT-expressing neurons in the paraventricular hypothalamic nucleus (PVN^OXT) were reduced following SD. Specific optogenetic activation of the PVN^OXT–CA2 pathway during encoding phase or PVN^OXT–PrL pathway during retrieval transiently restored SD-induced social memory deficits. Conversely, optogenetic high-frequency activation of PVN^OXT neurons enhanced the function of both PVN^OXT–CA2 and PVN^OXT–PrL pathways, promoting increased OXT release and providing sustained protection against SD-induced social memory deficits. These findings offer causal evidence that the PVN^OXT–CA2 and PVN^OXT–PrL pathways exert distinct modulatory roles in sleep-related social memory deficits and thereby nominate these pathways as precise targets for neuromodulation in sleep-related cognitive disorders.

Spinal cord injury (SCI) causes extensive neuronal loss, in which ferroptosis is critically involved. Although lipid transport at endoplasmic reticulum-mitochondria contact sites (ERMCSs) has been implicated in facilitating ferroptosis, the neuron-specific regulatory mechanisms remain elusive. Here, we show that neuronal ferroptosis is characterized by excessive ERMCS formation. Mechanistically, a systematic screening revealed the down-regulation of stearoyl-CoA desaturase 1 (SCD1), a critical enzyme in the synthesis of monounsaturated fatty acids (MUFAs) in neurons, following SCI (in vivo) or erastin treatment (in vitro). We demonstrated that SCD1 deficiency is the driving force behind aberrant ERMCS expansion, leading to increased lipid peroxidation and neuronal ferroptosis. Conversely, SCD1 overexpression could reverse these effects. Furthermore, we identified liver X receptor alpha (LXRα) as a direct transcriptional activator of SCD1. Pharmacological activation of LXRα with T0901317 upregulated SCD1 expression, which in turn restrained ERMCS formation, elevated MUFA levels, and ultimately inhibited neuronal ferroptosis. In murine SCI models, both adeno-associated virus-mediated neuronal SCD1 overexpression and LXRα agonist treatment effectively mitigated excessive ERMCS, reduced lesion size, preserved neuronal architecture, and improved functional recovery. Collectively, our study establishes the LXRα–SCD1 axis as a novel and druggable pathway for reducing neuronal loss and improving functional recovery by modulating ERMCS-dependent lipid exchange dynamics, revealing promising therapeutic targets after central nervous system trauma.

Exposures that disrupt the immune system can affect human health. This study aimed to understand immune variability influenced by exposures from the perspectives of systems biology and multiomics. We recruited 1,001 healthy participants and collected 183 exposures, 1,332 immunophenotypes, whole blood transcriptome, and plasma metabolome. Through exposure–immune wide association analysis, we identified 81 significant signals, with sleep and diet emerging as dominant exposures affecting the immunity. Sleep and diet influence the proportions of innate immune cells and the expression levels of immune cell surface proteins such as CD85j and CD16, respectively. Notably, distinct from the increase in interleukin-1β secretion caused by short-term late sleep onset, long-term late sleep onset triggered chronic inflammation with more metabolic changes. On the basis of the intracorrelation structure of exposure data, composite exposures were constructed and were found to have additional effects on immunophenotypes. Bidirectional mediation analysis revealed that sleep effects on immunity are commonly linked to the transcriptome, whereas dietary influences on immunity are primarily associated with the metabolome. We quantified the mediation effects of exposures, omics, and immunophenotypes and further demonstrated that these effects reflect human immune health or chronic diseases. Our study drew a comprehensive map of “exposure–immunome–omics” and is expected to provide guidance for future health assessment and management.

Hepatic encephalopathy (HE), a severe neurological complication of liver dysfunction, has long been regarded as a clinical issue confined to liver disease. However, recent clinical observations and basic research have revealed complex pathophysiological connections between HE and Parkinson’s disease (PD), 2 seemingly independent conditions. Patients with HE often exhibit irreversible extrapyramidal symptoms that closely resemble the motor disorders of PD; meanwhile, epidemiological studies suggest that individuals with liver disease—particularly non-alcoholic fatty liver disease (NAFLD)—may face an increased risk of developing PD. From the perspective of the gut–liver–brain axis, this study systematically explores the molecular mechanisms linking HE and PD, proposing a core hypothesis: HE creates a unique “neurotoxic soil” through ammonia toxicity, systemic neuroinflammation, and gut–liver–brain axis dysfunction. This soil may trigger PD in susceptible individuals, accelerate subclinical PD progression, or mimic PD-like pathology. The study analyzes in depth the direct regulatory role of ammonia in α-synuclein (α-syn) aggregation, the impact of liver disease-driven neuroinflammation on microglial activation and α-syn propagation, and the hypothesis of liver-derived α-syn transmission via the gut–liver–brain axis. It further discusses synergistic mechanisms such as manganese deposition, neurotransmitter imbalance, and gut microbiota metabolites. Based on these mechanisms, the study prospects translational medical applications, including the development of diagnostic biomarkers and novel therapeutic strategies such as “ammonia clearance plus” and gut–liver–brain axis targeting. This work provides new insights into how environmental metabolic factors contribute to neurodegenerative diseases and offers a theoretical basis for the combined prevention and treatment of HE and PD.

Understanding cellular dynamics requires real-time high-resolution imaging. Recent advancements in imaging technologies have provided unprecedented spatial and temporal resolutions, enabling the precise in situ monitoring of live-cell behavior. This review covers 4 advanced imaging modalities: stimulated emission depletion microscopy, structured illumination microscopy, single-molecule localization microscopy, and Raman spectroscopy. We summarize the principles, applications, advantages, and limitations of these methods, highlighting their significance for high-precision spatiotemporal monitoring of cellular structures and biochemical activities. These tools enable precise tracking of molecular interactions and analysis of cellular dynamics at the nanoscale, which is critical for understanding cellular physiology. The integration of these technologies into biomedical research has markedly enhanced our ability to observe live-cell processes, such as division, migration, differentiation, and signaling. The development and application of these high-precision imaging technologies hold substantial promise for improving disease diagnosis, therapeutic strategies, and drug discovery.

Mycotoxins are fungi-derived secondary metabolites that pose ecological and human health hazards. Deoxynivalenol (DON), as one of the most prevalent contaminating mycotoxins, has a detrimental impact on intestinal inflammation. Lycopene (LYC), a strong lipophilic carotenoid, is one of the most vital dietary antioxidants for human health. Thioredoxin-interacting protein (TXNIP), as a thioredoxin inhibitory protein, regulates NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation. We performed this work to probe the mechanisms by which LYC antagonizes DON-induced intestinal epithelium damage and the role of TXNIP in it. In the present study, we demonstrated that LYC relieved DON-induced structural and functional injury. We observed that LYC mitigated DON-induced inhibition of cell proliferation and cell cycle arrest, thereby delaying cellular senescence. LYC also mitigated DON-induced activation of TLR4/NF-κB/TNF-α signaling and inflammatory reaction. In addition, LYC prevented DON-induced up-regulation of TXNIP, thus inhibiting NLRP3 inflammasome activation and pyroptosis. Interestingly, TXNIP overexpression reversed the protective effect of LYC on DON-induced pyroptosis and senescence, but NLRP3 inhibitor restored these impairments. Our study suggested that LYC antagonized DON-induced intestinal epithelial cell senescence by suppressing TXNIP-mediated NLRP3 inflammasome activation. These findings show that TXNIP modulates intestinal function and thereby is a new curative molecule for intestinal diseases.

High-precision sensors are of fundamental importance in modern society and technology. Although there are various schemes for the construction of sensors relying on different physical mechanisms, obtaining sensors with higher levels of sensitivity and stronger robustness has always been expected. In particular, non-Hermitian quantum sensors have recently attracted substantial attention due to their unique properties. So far, 2 types of non-Hermitian sensors based on exceptional points and topological zero modes have been realized. Here, high-order exceptional bound states with robust properties are constructed for the first time. Based on these states, we propose theoretically and demonstrate experimentally another new type of non-Hermitian quantum sensors. Such sensors not only are robust against disorders but also have unprecedented sensitivity. Their sensing performance can display the improvement of many orders of magnitude over the previous non-Hermitian sensors. Furthermore, we design and fabricate such sensors based on circuit networks. Taking weak magnetic field detection as an example, we also experimentally demonstrate their sensing capabilities. Our work opens up new avenues for the development of highly sensitive sensors, which have a wide range of applications in various fields.

The growing demand for orthopedic implants, driven by an aging global population and the rising occurrence of bone abnormalities and defects, relies heavily on biocompatible titanium (Ti) and its alloys. However, their inherent biological inertness often results in poor osseointegration and increased vulnerability to bacterial infections, particularly those caused by biofilm-forming pathogens. Traditional antibiotic treatments frequently fail against biofilms and contribute to the escalating problem of antibiotic resistance, emphasizing the need for alternative therapies that do not foster resistance. Photodynamic therapy (PDT), which uses light-activated photosensitizers to generate reactive oxygen species (ROS) for effective bacterial eradication, presents a promising noninvasive strategy with high precision and low likelihood of resistance development. This review thoroughly explores the mechanisms of PDT and its application to Ti implants, focusing on both organic and inorganic photosensitizers. Moreover, considering current challenges, the study investigates approaches to improve PDT’s effectiveness in combating implant-related infections. These include optimizing PDT systems, developing new AIE-active photosensitizers, increasing oxygen supply to boost ROS production, combining multi-modal antibacterial treatments, and designing dual-functional implants. The review aims to identify current limitations and propose future directions, offering valuable insights to advance PDT-based strategies that enhance the antibacterial performance of Ti implants in the post-antibiotic era.

Autoimmune diseases (AIDs) are a group of immune-related disorders primarily affecting joints and surrounding tissues, often marked by chronic inflammation and autoimmune activation. Common types include systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, autoimmune cardiovascular diseases, and skin conditions. While their pathogenesis is unclear, recent studies suggest that abnormal gut microbiota may contribute. Previous research has shown that various patients with rheumatic disease exhibit altered gut microbiota, characterized by decreased microbial diversity, overall compositional changes, and microbiota-mediated functional alterations. Bacterial species closely associated with AIDs include Prevotella copri, Ruminococcus gnavus, and Ligilactobacillus salivarius. Dysregulated gut microbiota activates host immune responses through multiple mechanisms, including compromised intestinal barrier, systemic translocation, molecular mimicry of self-antigen epitopes, and changes in microbiota-derived metabolites, thereby substantially contributing to the development and progression of AIDs. Microbial metabolites, including short-chain fatty acids, tryptophan metabolites, and bile acid metabolites, are actively involved in driving disease progression. In addition, the therapeutic outcomes and adverse effects of immunotherapeutic agents can be modulated by gut microbiota through their impact on drug biotransformation processes. Clinically, analyzing gut microbiota characteristics can aid in disease diagnosis and prognosis prediction. Therapeutic strategies such as fecal microbiota transplantation, probiotics, prebiotics, and the Mediterranean diet may become effective measures for managing AIDs. This article reviews recent research progress, future directions, and the potential of microbiota-based interventions in treating AIDs.

Bioplastics derived from renewable food crops or agricultural feedstocks are alternatives to petrochemical materials, but it is challenging to balance their mechanical properties, thermal stability, and shapeability. Here, we report a thermally stimulated supramolecular bioplastic that employs polyethylene glycol to optimize the assembly of cellulose and polyvinyl alcohol molecules. The resulting bioplastic showed a reinforced supramolecular architecture, with a mechanical elastic modulus of 3.23 GPa and an impact resistance higher than 8.15 kJ·m⁻¹. It also showed thermal stability from −40 to 135 °C while maintaining its structural integrity and toughness, giving it potential applications for various shaping processes, including weaving, pouring, and molding. The bioplastic could also undergo natural soil biodegradation within 55 d and exhibited promising recyclability and economic feasibility. This study provides a strategy for configuring supramolecular structures and enhancing the design and manufacture of bioplastics with optimal comprehensive properties.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the leading cause of chronic liver disease globally and constitutes an independent risk factor for cardiovascular disease and mortality. Paeoniflorin (PF), the primary active compound derived from the traditional Chinese herb Paeonia lactiflora Pall., demonstrates multiple pharmacological activities. However, its anti-MASLD mechanisms remain incompletely elucidated. This study revealed that PF markedly ameliorates MASLD pathology by reducing hepatic lipid accumulation, inflammation, and fibrosis; ameliorating insulin resistance and liver function parameters; modulating key lipid metabolism genes (acetyl-coA carboxylase [ACC], sterol regulatory element-binding protein 1 [SREBP1], peroxisome proliferator-activated receptor gamma [PPAR-γ], fatty acid synthase [FASN], carnitine palmitoyltransferase 1 [CPT1], peroxisome proliferator-activated receptor alpha [PPAR-α], adipose triglyceride lipase [ATGL], and cluster of differentiation 36 [CD36]); decreasing pro-inflammatory factors (interleukin-1β [IL-1β], IL-6, tumor growth factor-α [TGF-α], and monocyte chemoattractant protein-1 [MCP-1]); and suppressing hepatic fibrosis markers (alpha-smooth muscle actin [α-SMA], tissue inhibitor of metalloproteinases-1 [TIMP1], collagen type I alpha 1 chain [COL1α1], fibronectin 1 [FN1], platelet-derived growth factor receptor beta [PDGFRβ], and plasminogen activator inhibitor-1 [PAI-1]). Through integrated transcriptomics and pharmacological overexpression approaches, we identified the SYK/SH3BP2 signaling pathway as the crucial mechanism driving MASLD pathogenesis. PF effectively attenuated hepatic metabolic dysregulation, inflammation, and fibrotic activation through inhibition of this pathway. Our work provided the first evidence establishing the SYK/SH3BP2 signaling axis as a pivotal pathway in MASLD progression, unveiling novel therapeutic targets while furnishing a mechanistic foundation for PF’s potential application in MASLD treatment.

Irreversible electroporation (IRE) is a nonthermal ablation modality used clinically for treating unresectable tumors while preserving vital structures through controlled application of pulsed electric fields. Previous data suggest that patient outcomes are enhanced with the induction of an anti-tumor immune response, but current research focuses on using immune checkpoint inhibitors, which function through conventional immune pathways that may be down-regulated by cancer or dysregulated by chemo-induced lymphodepletion. Chimeric antigen receptor (CAR) T cells overcome this limitation, as they are engineered with synthetic receptors that redirect lymphocytes to recognize and target cells expressing tumor-specific structures. CARs are engineered to have an increased binding affinity compared to in situ T-cell binding, amplify internal stimulation cascades, and release pro-inflammatory cytokines that can modulate the endogenous immune system. However, there are still major limitations for adoptive cell therapies in solid tumors, including life-threatening on-target off-tumor cytotoxicity, antigen escape, and failure to infiltrate and persist in solid tumors. Given the substantial evidence that IRE overcomes many of the challenges associated with immune infiltration and persistence in solid tumors, there is a strong premise for using targeted cell therapies following IRE, which would then target residual cancer that could repopulate the lesion. Here, we present the first proof-of-concept combination of IRE with CAR T cells. We validated that the cell membrane CAR target is not affected in electroporated cells that survive IRE, allowing for subsequent binding and elimination of residual tumor. The research demonstrates the feasibility and synergy of a novel combination of 2 clinically used techniques.

Neurodegenerative diseases (NDDs) are characterized by the progressive degeneration of specific neuronal populations, remain incurable, and impose an escalating global health burden due to aging populations. While therapeutic options had expanded in recent years, their overall efficacy remained limited. Neuroinflammation emerged as a central factor in the pathogenesis of NDDs. Hydrogen sulfide (H₂S), an endogenous gasotransmitter known for its potent anti-inflammatory properties, gained attention as a potential therapeutic agent. This review provided a comprehensive overview of the role of neuroinflammation in NDDs, elucidated the molecular mechanisms through which H₂S exerted its anti-inflammatory effects, and discussed recent advancements and potential clinical applications. Special emphasis was placed on the modulation of glial activity, disruption of the blood–brain barrier, regulation of the gut–brain axis, and the interplay between mitochondria and inflammasomes. Furthermore, the review integrated preclinical data on dose–exposure–response relationships to define the therapeutic window of various H₂S donors. It also explored the potential of spatial multiomics and microbiota-targeted approaches to facilitate more precise H₂S-based interventions. These insights provide important scientific merit for elucidating the mechanisms of NDDs and hold urgent practical relevance for developing novel therapeutics to mitigate disease progression.

Gastric cancer (GC) remains a leading cause of global cancer mortality. Analysis of clinical tissues and multiple cohorts (TCGA, ACRG, Singapore, KUGH) associated high RBM15 expression with favorable prognosis. Functional assays in vitro and in vivo demonstrated that RBM15 suppresses GC cell proliferation, migration, and invasion. Integrated RNA-seq and bioinformatics analyses identified the oncogene ECT2 and the epithelial–mesenchymal transition (EMT) pathway as key downstream effectors of RBM15. Mechanistically, RBM15 regulates the m6A methylation of ECT2 mRNA at the 2,909-base pair site, which modulates its binding to the reader protein IGF2BP3, as confirmed by MeRIP, RIP-qPCR, and RNA pull-down assays. A luciferase reporter assay further validated that this m6A modification regulates ECT2 expression. Furthermore, animal and patient-derived organoid models revealed that RBM15 enhances the sensitivity of GC to 5-fluorouracil (5-FU) chemotherapy in an ECT2-dependent manner. In conclusion, this study defines a novel RBM15/IGF2BP3–ECT2 signaling axis that regulates EMT and chemosensitivity in GC via m6A methylation, providing both mechanistic insights and a potential therapeutic strategy.

Achieving both selective pollutant degradation and real-time detection within a single micromotor system remains challenging for environmental monitoring. To address this limitation, we engineered gold-nanostar-decorated, molecularly imprinted BiVO₄ micromotors that combine simultaneous capture, photocatalytic degradation, and in situ detection of pollutants via surface-enhanced Raman spectroscopy (SERS). Plasmonic gold nanostars provide strong SERS enhancement for real-time tracking of pollutant degradation, while micromotors maintain autonomous propulsion under visible light irradiation. Surface molecular imprinting ensures selective recognition of rhodamine 6G and synergistically improves both photocatalytic and sensing performance. This multifunctional design establishes an all-in-one micromotor platform that bridges environmental remediation and on-board monitoring, opening opportunities for advanced water treatment technologies.

Lightweight multifunctional aerogels hold great promise in applications, e.g., electromagnetic microwave absorption, thermal insulation, and acoustic damping. However, conventional aerogels often suffer from limited functionalities, complicated manufacturing, and poor sustainability. Metal-organic frameworks (MOFs), with tunable porosity and abundant active sites, offer a compelling route to high-performance multifunctional aerogels, but it has remained a grand challenge to develop sustainable multifunctional MOF-based aerogels. Here, we report a sustainable multifunctional bio-aerogel (Ni-CCA) by integrating hierarchical scale-like topological Ni-MOF-NH₂ with cellulose through simple pretreatment using deep eutectic solvent followed by stepwise assembly–carbonization. The resulting aerogel features an ultralow density and a 3-dimensional layered porous structure. With 5 wt.% filler loading, Ni-CCA achieves a minimum reflection loss (RL_min) of −53.47 dB and an effective absorption bandwidth of 4.42 GHz, along with a radar cross-section suppression of 27.90 dB·m². Additionally, Ni-CCA shows enhanced flame retardancy (64.3% reduction in peak heat release), low thermal conductivity [33.3 mW/(m·K)] and improved acoustic damping (NRC of 0.31, 15 to 23 dB attenuation). The multifunctionalities of this bio-aerogel stem from its hierarchical architecture and synergistic loss mechanisms, offering a promising strategy for creating the next generation of lightweight multifunctional protective materials.

The development of efficacious pain management strategies remains a pivotal challenge, requiring the creation of sustainable, biomass-derived interfaces for real-time techniques. Existing assessment approaches are either invasive, rendering them inappropriate for extended home-based monitoring, or dependent on patient-reported subjective evaluations. In this study, we fabricated a multifunctional biomass-inspired polydopamine-based hydrogel (polyvinyl alcohol [PVA]/polyacrylamide [PAM]/lithium chloride [LiCl]/polydopamine [PDA]/lidocaine hydrochloride [LiH]) wearable patch. Encapsulating lidocaine, a local anesthetic, this biomass-composite patch integrated pain-sensing-assisted assessment and treatment functionalities. It exhibited remarkable properties, including good stretchability (534.22%), low modulus (0.044 kPa), fine tissue adhesion (1.82 kPa), high conductivity (3.90 S m⁻¹), rapid self-healing ability, and antibacterial properties. The patch enabled accurate sensing of diverse motion-related signals. Combined with deep learning algorithms, patients diagnosed with scapulohumeral periarthritis and lumbar diseases were recruited as volunteers for pain signal monitoring and evaluation (accuracy rate ~100%). Moreover, the hydrogel patch prolonged local photothermal analgesia in paw withdrawal threshold (>31% vs. Ctrl) and cumulative pain score (<10) by using a mouse plantar incision pain model. PVA/PAM/LiCl/PDA-based hydrogels elicited no detectable skin irritation or sensitization under the tested conditions. Therefore, this work not only pioneers the construction of a wearable integrated patch for pain management featuring “AI-assisted sensing evaluation” and “on-demand therapy”, but also provides a highly promising intelligent solution based on biomass-derived patches for the objective and prospective assessment and treatment of various types of pain.

The worldwide decline in male fertility represents a growing public health challenge, with fluoride exposure recognized as a key environmental factor exacerbating this decline. Fluoride hurts male reproduction, yet the specific mechanism remains unclear. Here, we demonstrate that fluoride reduced mouse sperm quality, destroyed the structure of testicular tissue, and caused severe damage to testicular somatic cells (Leydig and Sertoli cells). Meanwhile, the number of autophagosomes increased in Leydig cells and decreased in Sertoli cells. Network toxicology and functional analysis identified miR-34a-5p as the pivotal miRNA orchestrating fluoride-induced autophagic imbalance in testicular somatic cells. REST was identified as a novel miR-34a-5p target gene exhibiting pro-autophagic activity. Fluoride down-regulates miR-34a-5p and up-regulates REST in Leydig cells, whereas it exerts the opposite effects in Sertoli cells. The rescue experiment elucidated specific mechanisms: Fluoride down-regulates miR-34a-5p in Leydig cells, thereby derepressing REST to activate autophagy. Conversely, in Sertoli cells, fluoride up-regulates miR-34a-5p to suppress REST expression and inhibit autophagy. Collectively, the present study reveals an important mechanism underlying fluoride-induced male reproductive toxicity and provides a potential therapeutic target.

Radiotherapy (RT) and photodynamic therapy (PDT) for breast cancer are limited by tumor hypoxia and suboptimal photosensitizer performance. We developed folate-modified copper-doped carbon dots and loaded them with 5-aminolevulinic acid (ALA) to yield FCA, a nanoplatform that executes cascade nanozyme activities to remodel the tumor microenvironment: decomposing H₂O₂ to relieve hypoxia, generating hydroxyl radicals and singlet oxygen (¹O₂), and depleting glutathione (GSH). This priming enabled efficient ALA-to-protoporphyrin IX conversion, which subsequently amplified reactive oxygen species generation. The elevated oxidative stress then synergized with RT to accumulate DNA double-strand breaks and trigger cell cycle arrest. Consequently, FCA-PDT-RT reduced 4T1 cell viability to 20.09% and induced 83.82% apoptosis outcomes mechanistically linked to nuclear factor erythroid 2-related factor 2 (NRF2)–Kelch-like ECH-associated protein 1 (KEAP1)–heme oxygenase 1 (HMOX1) pathway activation. Despite compensatory upregulation of antioxidant genes (HMOX1 and glutamate–cysteine ligase modifier subunit [GCLM]), intracellular GSH and adenosine triphosphate were severely depleted, establishing a metabolic crisis wherein synthesis could not match consumption. This redox/energy collapse drove the pronounced cytotoxicity observed. In an orthotopic 4T1 model, FCA-PDT-RT achieved superior tumor control at only 12 Gy, which correlated with increased CD3⁺/CD8⁺ T cell infiltration and suppressed angiogenesis, while maintaining favorable safety. FCA thus enables synergistic PDT-RT through sequential microenvironment remodeling, oxidative amplification, and metabolic exhaustion, offering a dose-sparing strategy with translational promise for breast cancer therapy.

Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia (SCZ) represent major neurodevelopmental disorders with distinct typical ages of onset. These disorders exhibit substantial genetic and phenotypic overlap, yet their shared and disorder-specific neurobiological mechanisms remain unclear. We analyzed resting-state functional magnetic resonance imaging data from 2,176 participants (ASD, ADHD, SCZ, and healthy controls). Using heterogeneous matrix factorization, we extracted meta-blood-oxygen-level-dependent signals to reduce individual heterogeneity and constructed functional connectivity networks. Partial least squares identified a shared transdiagnostic abnormal connectivity pattern (STACP) and disorder-specific connectivity deviations (DSCDs). We annotated edges with transcriptomic, neurotransmitter, and mitochondrial maps for biological interpretation. The STACP involved connections linking deep regulatory systems (cerebellum, brain stem, and subcortical network) and cortical perceptual–executive networks (default mode, visual, frontoparietal, and somatomotor). The DSCDs of ASD and ADHD implicated overlapping networks with opposite functional connectivity directions (decreased in ASD and increased in ADHD), while SCZ showed more widespread desynchronization. STACP-related genes were enriched for synaptic development, cytoskeletal remodeling, and lipid metabolism, expressed in midbrain and deep-layer cortical neurons, and associated with serotonin transporter and cytochrome c oxidase. DSCDs were linked to glutamatergic plasticity and immune activation in ASD, dopaminergic regulation and glia–neuron interactions in ADHD, and broad synaptic plus immune–metabolic dysregulation in SCZ. Together, these findings provide a systems-level characterization of shared and disorder-specific neurobiological features across major neurodevelopmental disorders observed at different life stages.

Alkaline zinc–ferricyanide flow batteries (AZFFBs) emerge as promising candidates for long-duration energy storage. However, at cryogenic temperatures, these systems suffer from electrolyte solidification, anodic zinc dendrite formation, zinc-related side reactions, and cathodic Fe(CN)₆⁴⁻ precipitation-induced capacity decay. Herein, we propose a synergistic solvation strategy in which Li⁺ and Cl⁻ jointly inhibit the formation of tetrahedral hydrogen bond networks, thereby lowering the liquid–solid transition peak temperature of both the anolyte and catholyte. Meanwhile, Cl⁻ is utilized to construct a water-poor solvation structure around Zn(OH)₄²⁻ to optimize zinc deposition and inhibit the side reactions, while Li⁺ enhances the solubility of Fe(CN)₆⁴⁻ by incorporating additional water molecules into its solvation structure through strong ion–dipole interactions. The optimized AZFFB exhibits outstanding low-temperature performance, achieving stable cycling at −20 °C with an average coulombic efficiency of 99.54%. It also demonstrates excellent stability at room temperature, sustaining over 500 cycles at 28 °C with an average coulombic efficiency of 99.79%, representing more than a 22-fold extension in cycle life. Additionally, the AZFFB exhibits robust stability under fluctuating temperature conditions. These breakthroughs markedly enhance the potential of AZFFBs as viable solutions for extreme-environment energy storage, particularly in polar region microgrids, cold-climate off-grid power systems, and subsea power applications.

Protein secretion plays a crucial role in numerous biological processes, yet its underlying mechanisms remain incompletely understood. This study investigates the role of Sec72, a component of the Sec complex in Saccharomyces cerevisiae, in protein targeting and translocation to the endoplasmic reticulum. We discovered that deleting SEC72 significantly enhances the secretion of proteins with strongly hydrophobic signal peptides (SPs), accompanied by observable changes in cellular functions, such as iron homeostasis, cell wall assembly, and protein synthesis. Importantly, we identified specific gene modifications that, in combination with SEC72 deletion, enable a yeast strain to secrete α-amylase up to 6.5 g/l in fed-batch fermentation. These findings deepen our understanding of SP-mediated protein translocation and provide a basis for optimizing yeast hosts for more effective protein production.

Lithium-ion batteries (LIBs) are central to sustainable energy systems but are vulnerable to thermal runaway (TR), necessitating robust safety monitoring. Conventional single-sensor systems cannot decouple the coupled electrochemical, thermal, and mechanical processes, while existing multimodal sensors suffer from signal cross-talk and large footprints in practical applications. Here, we introduce an insect-inspired, self-decoupling multimodal sensor, fabricated via maskless laser direct writing, that leverages distinct sensing mechanisms and orthogonal output signals for simultaneous strain, temperature, and gas detection. The sensor achieves reliable intrinsic decoupling of strain and temperature over 20 to 110 °C, along with an independent gas response. Seamlessly integrated onto lithium iron phosphate (LiFePO₄) cells, it captures real-time multimodal data during both normal and TR events. Coupled with a bespoke multiphysics model, this platform reconstructs the thermal–mechanical evolution of LIBs. Our work provides a compact and durable strategy for precise real-time monitoring and early warning of battery failure.

Upon tumor metastasis, lymph nodes (LNs) undergo mechanical stiffening, yet how this change influences T cell activation within the microenvironment remains incompletely understood. In particular, the dynamic mechanical forces during activation are transduced by cell–extracellular matrix (ECM) interactions, while cell–cell interactions persist. Here, we established a novel T cell culture platform using hydrogels with tunable stiffness and decoupled presentation of RGD peptide and anti-CD3 monoclonal antibody, separately mimicking ECM–T cell and T cell–antigen-presenting cell interactions. This platform closely mimics the LN microenvironment during T cell activation. By integrating experiments with mathematical modeling, we revealed that T cells sensed mechanical changes in the microenvironment requiring RGD/integrin ligation, while stiff matrix up-regulated F-actin aggregation instead of myosin contraction, deforming the nucleus and promoting yes-associated protein nucleus translocation, resulting in interleukin-2 expression and T cell activation. Our findings shed light on the mechanobiological mechanism underlying the potential benefits of immunotherapy in patients with LN metastases and provide an optimized mechanical platform for studying T cell activation and expansion in vitro.

Humanoid robots possess the potential to solve complex problems across diverse environments, such as nuclear-contaminated zones, epidemic-affected areas, and extraterrestrial missions. However, a humanoid robot is an inherently complex system that integrates multiple disciplines, including perception, mechanical design, materials science, and motion control, each of which requires comprehensive and in-depth investigation. Among these aspects, motion control plays a crucial role, as it directly determines the robot’s motion accuracy, stability, and flexibility. In recent years, with the rapid evolution of graphics-processing-unit-based parallel computing and high-fidelity simulation environments, various deep-reinforcement-learning (DRL)-based approaches have been proposed to achieve precise and robust motion control due to its flexibility and adaptability in uncertain and dynamic environments. However, the inherent complexity and uncertainty of real-world tasks pose substantial challenges when designing effective reward functions for DRL agents. Most current methods typically rely on manually engineered or externally tuned reward signals and therefore require considerable domain expertise, associated with considerable human efforts and a long convergence time; these issues may even trigger mission failure. This work proposes an automatic reward learning method to derive reward functions for DRL in humanoid robot locomotion control. Specifically, a bilevel optimization framework is developed to enable automatic reward learning during policy learning. The reward learning mechanism in the upper level adaptively constructs and optimizes the reward function. The DRL framework in the lower level learns the locomotion control policy using the learned reward function. Three sets of experiments are conducted to verify the effectiveness of the proposed approach: training soft actor-critic and proximal policy optimization agents in MuJoCo environments, training the proximal policy optimization agent in a humanoid robot environment built with Isaac Lab, and transferring the agent to the real-world Unitree G1 humanoid robot through sim-to-real. The experimental results demonstrate that the proposed automatic reward learning method substantially improves learning efficiency and achieves superior performance to manually designed reward functions in both simulation and real-world deployment. By enhancing the success rate of transferring control policies from simulation to real-world humanoid robots, this approach provides a promising pathway toward accelerating the deployment of stable and adaptive humanoid robots in practical applications.

In response to the disparity between the notable biological efficacy and systemic toxicity of celastrol (Cel), this study established a synergistic delivery system (Cel/Lipo+/BHMs) that integrates Bletilla striata polysaccharide (BSP) and hyaluronic acid biomimetic lubricating double-cross-linked microgels (BHMs) infused with Cel cationic liposomes (Cel/Lipo+). The objective is to collaboratively attain attenuation, sustained retention, and reconfiguration of the immunological milieu for the treatment of osteoarthritis. Cel/Lipo+ selectively targets chondrocytes via electrostatic interactions, hence improving Cel delivery and reducing off-target damage. Biolubrication by BHMs reduces friction and markedly extends the drug’s retention duration within the joint cavity. In vitro studies have shown that Cel/Lipo+/BHMs possess excellent biocompatibility, enhance the proliferation and migration of chondrocytes, diminish oxidative stress, and work in conjunction with Cel/BSP to modulate macrophage reprogramming while suppressing the release of proinflammatory factors tumor necrosis factor-α and interleukin-1β. In a rat osteoarthritis model induced by monosodium iodoacetate, Cel/Lipo+/BHMs effectively mitigated cartilage degeneration by synergistically suppressing the inflammatory response, diminishing the expression of the cartilage degradation enzyme matrix metalloproteinase 13, enhancing the synthesis of type II collagen and aggrecan, and ameliorating subchondral bone microstructure. The therapeutic efficacy markedly exceeds that of either Cel/Lipo+ or BHMs individually, thereby emphasizing the primary benefits of the multitiered collaborative mechanism of the delivery system.

Postmenopausal osteoporosis and depression often occur together, but a single treatment that improves both conditions is currently lacking. The loss of estrogen can trigger oxidative stress, damage mitochondria, and drive dysregulated autophagy with impaired flux, simultaneously harming bone and the brain. We evaluated whether total flavonoids from Drynaria fortunei (TFDF) could counter these problems by activating sirtuin-1 (SIRT1), a protein that supports autophagy and mitochondrial health. In menopausal and chronic stress model mice and in cultured bone-forming cells and hippocampal neurons exposed to oxidative injury, we measured bone structure and strength indicators, mood-related behaviors, mitochondrial function, and gene activity patterns. The flavonoids preserved bone density and fine bone structure, shifted bone turnover toward formation, and improved depression-like behaviors (greater exploration and sucrose preference, less immobility). Across bone and the brain, TFDF modulated SIRT1–FOXO3–DEPP1 signaling and FOXO-linked oxidative stress and autophagy programs, thereby normalizing autophagic recycling and mitochondrial function. In cellular models, TFDF preserved mitochondrial function and restored autophagic recycling, and the loss or gain of SIRT1 function abolished or enhanced these benefits, respectively, indicating that SIRT1 activity is necessary for the effects of TFDF. These findings identify TFDF as a single, mechanism-based strategy that addresses both skeletal deterioration and depressive symptoms after menopause by engaging SIRT1-dependent stress autophagy pathways to restore cellular recycling and energy control.

Brain metastasis (BrM) is a common occurrence in lung cancer and substantially worsens the prognosis due to the blood–brain barrier (BBB), which restricts drug entry into the brain. Here, we found that exosomes secreted by lung cancer cells that had acquired epidermal growth factor receptor tyrosine kinase inhibitor resistance and undergone epithelial–mesenchymal transition (osimertinib- and WZ4002-resistant H1975) exhibited enhanced brain-specific distribution and a concomitant increase in BrM compared with exosomes from parental H1975 cells. To identify exosomal mediators of this phenotype, liquid chromatography-tandem mass spectrometry-based proteomic analysis was performed. Exosomes derived from resistant cell lines exhibited distinct protein profiles relative to parental cells, with 744 exosomal proteins significantly altered (fold change ≥ 2; P ≤ 0.05). Prioritization of membrane proteins and ligand–receptor interaction analysis identified ITGAV (integrin αV), ITGB3 (intergrin β3), and L1CAM (L1 cell adhesion molecule) as candidates interacting with brain-specific ligands, including neural cell adhesion molecule 1 (NCAM1) and contactin 2. Validation of exosomal association by Western blotting identified ITGB3 and L1CAM as final candidates. Subsequent functional modulation studies demonstrated that exosomal L1CAM plays a dominant role in brain distribution and metastatic progression. Exosomal L1CAM increased BBB permeability by disrupting endothelial tight-junction integrity both in vitro and in vivo. This effect was associated with the involvement of NCAM1 on BBB endothelial cells, as suggested by an exosomal L1CAM masking experiment. Clinically, exosomal L1CAM demonstrated diagnostic potential for BrM (area under the curve [AUC] = 0.80), and a combined exosomal L1CAM/ITGB3 panel significantly improved diagnostic accuracy (AUC = 0.98). Collectively, these findings identify exosomal L1CAM as a key regulator of brain-specific metastasis and support the clinical utility of the L1CAM/ITGB3 panel as a noninvasive biomarker for BrM in lung cancer.

Direct generation (DG) technologies—comprising dielectric elastomer generators (DEGs) and dielectric fluid generators (DFGs)—offer a promising paradigm for ocean wave energy conversion by integrating transduction mechanisms directly into wave-responsive materials. This assessment provides a comprehensive analysis of DG systems, outlining their working principles, recent material innovations, and comparative performance in harsh marine environments. We examine advancements in dielectric materials, including silicone-based and emerging nonsilicone elastomers, and discuss their influence on energy density, electromechanical efficiency, and environmental resilience. Comparative assessments highlight the advantages of DFGs in long-term durability and energy conversion under complex wave dynamics, while DEGs remain competitive due to their mechanical flexibility and scalable fabrication. The review concludes with a discussion of hybrid system integration, challenges in large-scale deployment, and a roadmap toward commercialization. By synthesizing current research trajectories, this article aims to accelerate the transition from laboratory-scale prototypes to deployable, cost-effective ocean energy harvesting solutions.

The persistence of castration-resistant prostate cancer (CRPC) despite androgen deprivation therapy and androgen receptor (AR) signaling inhibition underscores the need to elucidate resistance mechanisms. The AR signaling pathway plays a central role in the development of prostate cancer. Metabolic reprogramming of androgen synthesis and aberrant activation of AR signaling collectively drive CRPC development. Under therapeutic pressure, AR signaling adapts through AR amplification, ligand-binding domain mutations, splice variants, and alternative activation by cytokines/growth factors, maintaining AR transcriptional activity in low-androgen environments. Concurrently, somatic alterations (like PTEN loss) and crosstalk with key pathways such as PI3K/AKT, coupled with the evolving multifocal spatial heterogeneity, further complicate the role of AR signaling in CRPC treatment resistance. Innovations in single-cell and spatial technologies reveal tumor heterogeneity and lineage plasticity governed by genetic and epigenetic alterations. Current therapeutic innovations, including approaches such as CYP11A1 inhibition, targeting of the AR N-terminal domain, and bipolar androgen therapy, are showing promise in clinical trials. Overcoming CRPC effectively requires cotargeting androgen/AR-associated pathways and suppressing lineage plasticity through dynamic monitoring and precision interventions.

Hypoxia promotes oral squamous cell carcinoma (OSCC) progression by disrupting redox equilibrium; however, how tumor cells precisely calibrate prosurvival reactive oxygen species levels remains unclear. This study identifies a hypoxia-inducible signaling axis centered on the posttranslational crotonylation of the molecular chaperone heat shock protein 90 alpha family class B member 1 (HSP90AB1), which stabilizes thioredoxin (TXN) to constrain oxidative stress. Hypoxia triggered the hypoxia-inducible factor-1α (HIF-1α)-dependent transcriptional up-regulation of acyl-CoA oxidase 1 (ACOX1), increasing the level of crotonyl-CoA to drive the site-specific crotonylation of HSP90AB1 at lysine 265 (K265cr). Molecular dynamics simulations revealed that K265 crotonylation induced the conformational compaction of HSP90AB1, strengthening its interaction with TXN and enhancing its stability. This chaperone–client axis effectively buffers reactive oxygen species to protumorigenic thresholds, promoting proliferation and conferring cisplatin resistance. Clinically, HIF-1α/ACOX1/HSP90AB1 K265cr/TXN pathway activation is correlated with advanced disease and reduced survival in OSCC patients. Crucially, the HSP90AB1 K265R mutation or pharmacological inhibition of ACOX1 (10,12-tricosadiynoic acid) or TXN (1-methyl-propyl 2-imidazolyl disulfide, PX-12) synergizes with cisplatin to suppress tumor growth in vivo by disrupting redox adaptation. These findings reveal that crotonylation is a hypoxia-sensitive rheostat for TXN-mediated redox control, suggesting that the ACOX1–HSP90AB1–TXN axis is a therapeutic vulnerability in therapy-resistant OSCC.

The past decades have witnessed the rapid development of metamaterial or metasurface cloaks, with different kinds of fascinating invisibility in phase-amplitude restoring. However, available cloaks realized thus far belong to contact-based framework; namely, they should adhere to the targets rather than being apart from each other with arbitrary distance (termed noncontact ones hereafter), which suffered from several critical shortcomings in practice. Here, we first briefly summarized some of the most important milestone works toward contact-based cloaks and then cast a holistic outlook for the conceptual noncontact stealth framework using supportive reconfigurable intelligent surface (SRIS) cloaks. Such transformative paradigm is typically composed of several SRISs deployed far away from the targets, and equipped with artificial intelligence in terms of various microcomputers, sensors, and actuators. The disruptive cloak framework full of cutting-edge techniques such as multidimensional perception, integrated radiation and scattering, and integrated sensing and communication promises to afford a brand new avenue and platform for next-generation invisibility due to their unprecedented flexibility, adaptability, and empowerment of future cloaks in interdisciplinary fields.

Female reproductive disorders influence women’s physical and mental well-being, and the sustainability of the family. However, it is unclear whether lifestyle factors, including sedentary behaviors and physical activity, could impact them. Here, we performed sex-stratified genome-wide association studies of 5 lifestyle factors in European participants from UK Biobank, including self-reported leisure screen time (LST), sedentary behaviors at work and during commuting, time spent in driving, and daily physical activity. We identified 18 novel sex-stratified variants associated with these exposures and showed that LST was more heritable in women (8.6%) than in men (6.9%). Mendelian randomization (MR) analyses using women-related instruments on 4 female reproductive outcomes demonstrated that per 1-h longer LST a day was robustly associated with elevated risks of menorrhagia (odds ratio [OR] = 1.31, 95% confidence interval [CI] = 1.10 to 1.55), endometriosis (OR = 1.34, 95% CI = 1.11 to 1.60), polycystic ovarian syndrome (OR = 3.05, 95% CI = 1.65 to 5.65), and ectopic pregnancy (OR = 1.35, 95% CI = 1.11 to 1.65), while little evidence was found for sedentary behaviors at work or during commuting. Mediation MR showed that the associations with these outcomes were independent from body mass index, except polycystic ovarian syndrome. Nonlinear MR suggested that LST ≥4 h/day was robustly associated with increased risks of endometriosis and menorrhagia. The findings were independently validated using additional genetic data from the European population and survey data from the National Health and Nutrition Examination Survey. In summary, a simple and actionable lifestyle modification, sitting less, is likely to have independently beneficial influences on multiple reproductive disorders.

Aberrant expression or dysfunction of ribonucleoprotein (RNP) granules usually contribute to cancer initiation, progression, and therapeutic response. In the process, protein modification importantly mediates the interactions between cancer and RNPs/associated proteins. Therefore, we tried to summarize and discuss the complex interactions between RNPs and various protein modifications in cancers, facilitating the clinical translation of RNP-based therapies. Studies have shown that RNPs can directly undergo phosphorylation, ubiquitination, SUMOylation, methylation, crotonylation, and acetylation, but no studies have reported glycosylation, fucosylation, or PARylation on RNPs. These modifications can competitively occur on RNPs, affecting the RNP granule expression and function. Cancer cells, immune cells, and stromal cells can undergo RNP granule modifications, consequently mediating current treatment efficacy. These results provide the basis of RNP granule-based antitumor therapy. However, the structural complexity of RNPs and limited research depth pose significant key for clinical translation.

The maintenance and regulation of cancer stem cell (CSC) stemness are crucial for tumor progression; however, the mechanisms underlying tumor stemness regulation remain poorly understood. Herein, we discovered that the enhanced hypoxia-induced transforming growth factor beta induced protein (TGFBI) in bladder cancer (BLCA) promotes the establishment of a stemness loop in the tumor microenvironment, facilitating the maintenance of CSC stemness and malignant proliferation. Clinically, the upregulation of hypoxic TGFBI in BLCA correlates with malignant BLCA features and poor prognosis. Mechanically, TGFBI can stabilize the structural integrity of disulfide bonds in Cys48 and Cys77 of growth differentiation factor 15 (GDF15), leading to aberrant function activity of GDF15 and secretion. Interestingly, secreted GDF15 consequently not only further upregulates CSC-related gene expression but also induces the activation of cancer-associated fibroblasts through the transforming growth factor beta receptor type 2 (TGFBR2)–transforming growth factor β (TGFβ)–TGFBI self-regulatory feedback loop to promote stemness in BLCA. TGFBI knockdown or GDF15 inhibition results in a decrease in functional proteins associated with stemness maintenance, which suppresses bladder CSCs’ self-renewal and effectively improves the efficacy of chemotherapy. Together, these findings demonstrate the pivotal role of TGFBI in BLCA’s stemness maintenance and BLCA progression, highlighting that the inhibition of the TGFBI/GDF15 axis is a potential therapeutic strategy for the amelioration of cancer chemotherapy.

The overuse and misuse of antibiotics have led to widespread resistance in bacteria, which makes infections difficult to treat. The insufficient prevention measures, limited treatment options, and delayed antibiotic developments call for immediate global actions to discover effective and safe treatments for bacterial infections. Over the past decades, more and more studies have found that bacterial extracellular vesicles (BEVs) secreted by bacteria with nanoscale size, lipid bilayer structure, pathogen-associated molecular patterns, and inherent bioactive substances are the ideal candidates for bacterial infection treatment. Meanwhile, advanced engineering approaches have further endowed these BEVs with more customizable properties to effectively fight against bacterial infections. Herein, the present review begins with an overview of the biogenesis and biocomponents of BEVs to better comprehend their bioactivities against bacterial infections. Their isolation and engineering approaches are then introduced, with an emphasis on the diverse genetic, physical, and chemical strategies to functionalize them with desirable capacities for the optimal treatment of bacterial infections. Recent advances in exploring the natural BEVs as antibacterial and antiadhesion agents, as well as the engineered BEVs as vaccine antigens, vaccine adjuvants, and delivery nanocarriers, are expounded successively. Discussions on the new trend of engineering BEVs as nanoweapons to combat bacterial infections, in terms of advantages and challenges, are provided at the end to expedite these BEV-based therapeutic modalities for bacterial infections from bench to bedside.

Inflammatory arthritis, mainly including rheumatoid arthritis (RA) and ankylosing spondylitis (AS), is a group of chronic progressive autoimmune diseases that destroy joints. T helper 17 (Th17) cells are extensively involved in the joint inflammation as well as bone and cartilage destruction of these diseases. Previously, proviral integration site for Moloney-murine leukemia virus 1 (Pim1) was reported to be involved in various autoimmune diseases by mediating the proinflammatory effects of T cells. However, the pathological effect and the therapeutic potential of Pim1 in inflammatory arthritis remain elusive. The present study demonstrated that Pim1 expression was elevated in CD4⁺ T cells locally and systemically in patients with RA or AS and in 2 mice models of inflammatory arthritis. Conditional knockdown of Pim1 in CD4⁺ T cells (Pim1 cKO) or using the Pim1 inhibitor AZD1208 alleviated the development of inflammatory arthritis in association with decreasing the proportion of Th17 cells. In vitro experiments involving inhibition and overexpression confirmed the promoting effect of Pim1 on Th17 cell differentiation. Mechanistically, Pim1 phosphorylated mitochondrial calcium uptake protein 1 to increase mitochondrial calcium influx, which subsequently activated mitochondrial oxidative phosphorylation and promoted Th17 cell differentiation. Through molecular docking and dynamic simulation, nilotinib, a Food-and-Drug-Administration-approved drug, was identified as a selective substitute for the currently clinically nonapproved Pim1 inhibitors, which impeded Th17 cell differentiation and was well tolerated during the treatment of Pim1 cKO mice and 2 inflammatory arthritis mouse models. Our study contributes to a better understanding of the mechanism through which Pim1 promotes Th17 cell differentiation and advances the clinical application of Pim1 as an effective target for treating inflammatory arthritis.

Conventional metal oxide sensors often suffer from limited long-term stability over an ultrabroad temperature range, primarily due to their single-type active sites and a static electronic configuration. To overcome this limitation, we constructed a dual local electric field (LEF) with a graded electron concentration profile by precisely modulating the local chemical environment of CeO₂. This design introduces a thermally activated electric-field switching mechanism, which enables ultrafast and stable response value toward NO₂ detection from −50 to 800 °C. We demonstrate that at low temperatures, the divergent hybridization between Pt and Ce orbitals leads to a lower thermal activation energy for LEF-1 than for LEF-2. As temperature rises, electron migration from the 4f orbitals of Ce³⁺ to adjacent Ce⁴⁺ weakens LEF-1, whereas thermal activation promotes efficient electron transfer in LEF-2, allowing LEF-2 to dominate at high temperatures and ensuring continuous activity. This relay sensing mechanism sustains rapid response (within 12 s) and long-term stability (over 75 d) at both −50 and 800 °C. This work presents an adaptive sensing mechanism through electron gradient differentiation and thermal-driven field switching, offering a new paradigm for the design of intelligent sensors under extreme conditions.

The treatment of gram-negative bacterial infections remains a formidable challenge due to their resilient outer membrane and adaptive evasion mechanisms. Herein, we present a multifunctional nanozyme hydrogel, copper telluride@cationic guar gum (Cu_xTe@CG), which acts as a gram-negative-specific bactericidal platform. This hydrogel integrates the unique enzymatic and physical properties of urchin-like Cu_xTe nanozymes with the biocompatible and adhesive cationic guar gum (CG) matrix. The Cu_xTe@CG hydrogel exhibits synergistic oxidase- and glutathione peroxidase-like activities, catalyzing the generation of reactive oxygen species (ROS) while depleting bacterial glutathione, thereby inducing lethal oxidative stress. Crucially, transcriptome sequencing revealed that the platform specifically targets Pseudomonas aeruginosa by down-regulating key genes involved in lipopolysaccharide (LPS) biosynthesis and flagellar assembly, compromising their primary defense and motility structures. This targeted interference with LPS and flagella amplifies the ROS-mediated attack, leading to enhanced and specific killing of gram-negative pathogens (Escherichia coli, P. aeruginosa, and Klebsiella pneumoniae), effective biofilm disruption, and inhibition. In a P. aeruginosa-infected burn wound model, the Cu_xTe@CG hydrogel markedly accelerated healing by eliminating bacteria, promoting angiogenesis, and modulating inflammation, all while demonstrating excellent biosafety. This work establishes the Cu_xTe@CG hydrogel as a robust and targeted therapeutic strategy for combating stubborn gram-negative infections.

Most cancer metastases exhibit mutational profiles similar to those of the primary tumor. However, the nongenetic mechanisms driving metastasis remain poorly understood. Here, we show that lineage trans-differentiation is a hallmark of cancer metastasis. Bioinformatic tools capable of reconstructing cancer phenotypic evolutionary trajectories at single-cell resolution were developed, revealing a progressive loss of transcriptional and epigenomic lineage fidelity in cancer cells as they evolve toward metastasis. During premetastatic evolution, cells undergo de-differentiation into a fetal-like state. The mis-expression of alternative-lineage gene programs during re-differentiation from this fetal-like state leads to the formation of trans-differentiated metastatic cells. This trans-differentiation, rather than fetal-like transcription, constitutes a key feature of metastasis in both humans and mice. In clinical samples, trans-differentiation correlates with histopathological grade, metastatic potential, and patient survival. Additionally, trans-differentiation is associated with gain of oncogenic mitogen-activated protein kinase (MAPK) signaling and can be reversed through MAPK inhibition. These findings offer a detailed account of metastatic cancer evolution driven by epigenetic reprogramming while also uncovering the molecular mechanisms underlying this process.

Lumbar spine diseases substantially impact the patients’ quality of life, necessitating accurate and efficient diagnostic tools. This study presents Lumbar VNet Pro (LVP), the first real-time artificial-intelligence (AI)-assisted system embedded within MRI hardware for lumbar spine analysis, integrating deep learning with MRI. LVP was trained on 2,453 MRI datasets and validated both internally and externally across multiple centers. During the training (1,848 MRI datasets) and validation (605 MRI datasets), LVP exhibited outstanding performance in localization (Dice = 0.93), segmentation (Dice = 0.92), labeling (identification rate = 0.90), and timeliness (average inference time = 1.1 s). Following the successful construction of LVP, we conducted comprehensive testing through both internal and external multicenter evaluations. Internal testing involving 100 patients indicated that the recognition accuracy of LVP was as high as 100%, and the consistency between the LVP assessment and the manual assessment using the gold standard reached 97%. In external testing involving 1,522 patients, LVP’s diagnostic performance was compared to those of manual and human–machine-assisted methods. The AI-assisted approaches demonstrated better performance across multiple spinal pathologies, including lumbar disc herniation, spinal canal stenosis, and lateral recess stenosis, with area under the receiver operating characteristic curve values >0.95 for deep learning/human–machine approaches and >0.90 for the fully manual approach. The real-time integration of LVP with MRI scanning improved positioning accuracy and reduced interobserver variability, supporting its potential as an adjunct tool for enhancing MRI-based spine diagnostics. However, further studies are warranted to assess its generalizability across diverse clinical settings.

RNA has been established as an essential molecule in virtually all cellular processes. Besides its role in cellular modulation via extracellular vesicular release, it has long been thought to only exert its function intracellularly. Recent discoveries have shown evidence of extracellular RNA tethered to the cell surface of different cell types. These cell surface RNAs are predominantly modified with sialylated glycans, denominating them cell surface glycoRNAs. While the expression of cell surface glycoRNAs has been found on a wide array of immune cell and cancer cell types, research on its functional roles has only recently been explored due to challenges in detection, isolation, and sequencing of this new subclass of RNA. In this review, the history, biogenesis, detection and isolation techniques, and functional roles of cell surface RNA to date will be discussed, in addition to commenting on its translational capacity for studying immunomodulation and disease. Acknowledging the presence of cell surface RNAs and propelling our understanding on their function will provide a new avenue to study cellular modulation and cell–cell communication.

Foxtail millet (Setaria italica L.), a C4 cereal crop domesticated in China, exhibits exceptional nitrogen use efficiency (NUtE) with marked genotypic variation; however, the molecular basis remains underexplored. Here, we identified candidate genes through a sequential filtering strategy from genetic linkage (bulked segregant analysis sequencing) to transcriptional response (RNA sequencing) within defined quantitative trait locus intervals to dissect NUtE mechanisms in contrasting genotypes: the low-nitrogen-tolerant variety Yugu28 and the low-nitrogen-sensitive variety Qiyehuang, to identify the genetic regulatory mechanisms. Several candidate genes were screened, such as glutamine synthetase (GS2, Seita.3G024100), glutathione S-transferase (GLUS, Seita.3G386000) and nitrogen regulatory protein P-II (Seita.3G051900). Seita.3G051900 was identified as LOW-NITROGEN REGULATORY GENE (SiLNR1), which is highly expressed in different organs. The functional characterization revealed that SiLNR1 overexpression results in strikingly low-N resilience: Compared with the wild-type controls, the transgenic lines presented 106% longer primary roots, 91.3% greater plant height, and 18.9% greater root nitrogen accumulation under low-nitrogen (LN) conditions and boosted grain yield and NUtE by 29.5% and 24.3%, respectively. By contrast, the silnr1 mutant presented markedly shorter primary roots and plant height and lower shoot N accumulation under LN conditions. Field validation of the SiLNR1 allele in the recombinant inbred line population demonstrated that the SiLNR1 allele from Yugu28 confers a substantial and measurable yield gain under LN field conditions. The functions of SiLNR1 associated with enhanced nitrogen uptake and utilization have been revealed, indicating that SiLNR1 contributes to nitrogen metabolism and NUtE positively, thus providing a theoretical basis and application prospect for resource conservation, environmental protection, and sustainable agricultural development.

Antimicrobial peptides (AMPs), traditionally regarded as innate immune effectors, are increasingly recognized for their structural and functional convergence with pathogenic amyloids. Recent studies—including our own—reveal that AMPs not only exhibit antimicrobial activity but also modulate amyloid aggregation by accelerating, delaying, or redirecting fibril growth, acting at the nexus of protein misfolding, inflammation, and host defense. In this account, we highlight the emerging role of AMPs as cross-seeding modulators that can inhibit or promote amyloid fibrillization depending on structural context. We summarize mechanistic insights into how β-sheet-rich AMPs engage amyloidogenic targets via structural compatibility, directional seeding asymmetry, and surface-mediated catalysis. We also explore how AMP–amyloid cross-seeding contributes to a bidirectional pathogen–amyloid feedback loop, linking microbial infections to chronic inflammation and neurodegeneration. Building on these molecular foundations, we present recent design advances in engineering AMP-derived inhibitors with enhanced amyloid specificity, proteolytic stability, and translational potential. These dual-function peptides—capable of suppressing amyloid aggregation and modulating immune responses—offer a unique therapeutic strategy for diseases such as Alzheimer’s, type 2 diabetes, and systemic amyloidosis. We conclude by outlining current challenges and future directions for data-driven design, delivery optimization, and clinical development of multifunctional AMPs as next-generation therapeutics.

The origin of molecular chirality remains an enigma in chemistry, particularly regarding how single-molecule events overcome intrinsic stochasticity to establish population-level chirality. Here, we present a viable strategy for real-time, from-the-beginning single-molecule trajectory monitoring of asymmetric evolution from a single initial molecule with single-event resolution, allowing direct observation of spontaneous mirror symmetry breaking in a single-molecule Diels–Alder reaction system. We monitor the asymmetric evolution in real time using the chirality-induced spin selectivity effect. This approach enables the capture of initial symmetry breaking at the single-molecule level and the identification of the excess-compensation mechanism. In addition, the introduction of an external electric field to the symmetry-breaking species enables universal asymmetric synthesis without the need for a catalyst. The increase in the number of molecules leads to symmetry breaking, which is also contingent on the coupling with the external environment. This work deepens our understanding of the molecular principles underlying the origin of life and has many implications for precise chiral synthesis and drug design.

Solar-driven carbon dioxide (CO₂) reduction can sustainably produce chemicals and fuels but is often limited by rapid charge recombination and slow CO₂-to-product kinetics, typically necessitating homogeneous photosensitizers and cocatalysts. Here, we reported an integrated photocatalyst, TF-COF-CONH-Au₂₅-Co, constructed by immobilizing atomically precise Au₂₅ nanoclusters (NCs) on a covalent organic framework (COF) incorporating [Co(bpy)₃]²⁺ complex (Co–N₆ coordination). Under visible-light illumination, this hybrid catalyzes CO₂ conversion to syngas without external photosensitizers or cocatalysts, delivering a CO formation rate of 2,321.9 μmol·g⁻¹·h⁻¹ (turnover number of 171.9 and turnover frequency of 7.2 h⁻¹). The Au₂₅ NCs enhance light responsiveness and charge transfer efficiency, thereby enriching long-lived photogenerated electrons, while concurrently modulating the electronic state of Co sites to reduce the energy barrier for CO₂ reduction. This study illustrates a molecular-level strategy to synergistically integrate metal NCs, COFs, and [Co(bpy)₃]²⁺, showing a promising platform for high-performance photocatalytic CO₂ conversion.

Pancreatitis is a complex inflammatory disease with substantial genetic determinants. It progresses from acute to chronic forms and poses substantial clinical challenges due to a lack of disease-modifying therapies. Conventional treatments are largely palliative, highlighting the urgent need for mechanism-based interventions. Gene therapy represents a transformative strategy, directly targeting the root genetic causes. This review comprehensively outlines the current landscape and future directions of gene therapy for pancreatitis. We first delineate the genetic underpinnings of the disease, categorizing susceptibility genes into 4 key pathways involving lipid metabolism, trypsin regulation, ductal secretion, and endoplasmic reticulum stress. We then detail the core therapeutic strategies—gene augmentation, suppression, and editing—highlighting both clinically validated drugs (targeting lipid metabolism) and novel preclinical approaches for pancreatitis. Furthermore, to achieve pancreas-targeted delivery, we thoroughly describe the delivery vectors, including viral and nonviral systems, as well as the administration routes. However, translating these therapies faces considerable hurdles, such as physiological and pathological barriers to pancreatic targeting, the challenge of determining intervention timing, the lack of optimal animal models recapitulating human pancreatitis, and host immune responses. We discuss potential solutions to these hurdles, including innovative vector design, improved models, and immunotherapy. Ultimately, gene therapy holds the promise to fundamentally transform the pancreatitis treatment paradigm, offering a path from palliative care to definitive, precision medicine.

Drug resistance and impaired apoptosis limit durable responses in urological malignancies. Paraptosis is a regulated, nonapoptotic cell death program marked by prominent cytoplasmic vacuolization, typically driven by endoplasmic reticulum (ER) swelling and mitochondrial dysfunction. This perspective synthesizes emerging evidence in prostate, bladder, and renal cancers and proposes a stress-axis framework in which diverse inducers converge into 3 mechanistic classes: (a) proteostasis disruptors that precipitate acute ER stress, (b) ion-handling modulators that trigger lethal mitochondrial Ca²⁺ overload, and (c) redox regulators that amplify reactive-oxygen-species-driven proteotoxic stress. We discuss how natural products, repurposed agents, and delivery platforms can be integrated with chemotherapy, targeted therapy, or immunotherapy to overcome resistance and exploit death-pathway cross talk. Key translational priorities include defining pathway-specific biomarkers, mapping ER–mitochondrion signaling thresholds, and dissecting stress-buffering and cytoprotective autophagy as resistance mechanisms. Clarifying these principles may enable the context-specific exploitation of paraptosis across urological cancers and related diseases, in both primary and therapy-refractory settings.

Blood is a force-rich system. Beyond biochemistry, blood cells continually sense shear, stretch, and substrate rigidity, encode these inputs into biochemical and structural state changes, and adjust future behavior. We term this mechanical intelligence: an operational framework encompassing mechanosense, learning and memory, decision-making, and adaptive evolution. We synthesize evidence across red blood cells (RBCs), leukocytes, and platelets showing how mechanosensitive receptors (Piezo-type mechanosensitive ion channel component 1, glycoprotein Ib-IX-V complex, and integrins), cytoskeletal feedback, and nuclear effectors (Yes-associated protein/transcriptional coactivator with PDZ-binding motif and nuclear factor κB) couple mechanical cues to cellular states and functions (oxygen delivery, immune surveillance, and hemostasis). Repeated mechanical exposures produce mechanical memory (e.g., RBC fatigue and shape memory, shear-primed platelet hyperreactivity, and stiffness-modulated leukocyte transmigration) that improves performance in physiological contexts but contributes to pathology when dysregulated (vaso-occlusion, thrombosis, and inflammaging). We outline mechanodiagnostics (single-cell deformability cytometry, atomic force microscopy, and microfluidic thrombus profiling) and mechanotherapy (ion channel modulators, engineering cells, and mechanocompatible devices) and propose reporting standards, readiness levels, and validation pathways.

Miniature robots inspired by nature are appealing, and the achievement of their rapidity has become uncomplicated after years of development. However, one of the critical challenges of miniature robots is achieving rapidity and agile motions under high load capacity. To address this challenge, this work proposes a unique tripodal piezoelectric robot, featuring axisymmetric vibration modes and non-axisymmetrically arranged feet. On the one hand, by selecting appropriate vibration modes and arranging the 3 feet at unequal spacing, multidimensional and unequal amplitude actuation trajectories at different feet are achieved, enabling the robot to achieve agile motions. On the other hand, strong load capacity is realized through a high-stiffness ring base. The selected vibration modes and different actuation trajectories at foot ends are validated through simulation analysis. A prototype of the robot is developed, and a miniature specialized power supply is designed and integrated into the robot. The wireless linear and rotational speeds reach 93 mm/s and 438°/s, respectively, and the load capacity reaches 200 g, while the resolution is 0.63 μm. Owing to its small size, high load capacity, high resolution, and agility, the robot demonstrates potential for micro-manipulation applications and motion capabilities in confined spaces.

Portal vein tumor thrombus (PVTT) is among the most lethal complications of hepatocellular carcinoma (HCC), yet its molecular mechanisms and immune features remain poorly characterized. To address this gap, we performed a comprehensive multi-omics analysis of 99 specimens from 47 patients, integrating nCounter profiling, single-cell RNA sequencing, digital spatial profiling, and proteomics to construct the first spatial map of the PVTT microenvironment. These analyses revealed marked intratumoral heterogeneity and enrichment of myofibroblast-like cancer-associated fibroblasts (myCAFs) arising through a macrophage-to-myofibroblast transition. Nidogen-1 (NID1) was identified as a stromal driver of immune barriers, highly expressed in PVTT cores and associated with impaired antitumor immunity. Guided by these mechanistic insights, we repurposed acarbose, a Food and Drug Administration-approved drug, to inhibit the NID1 axis. Functional assays demonstrated that acarbose disrupted myCAF-mediated immune barriers, suppressed PVTT progression, and synergized with anti-programmed death-1 (anti-PD-1) therapy in preclinical models. Furthermore, analysis of an independent clinical cohort of 810 HCC patients revealed a substantially lower incidence of PVTT among those receiving acarbose, underscoring its translational potential. Collectively, these findings establish the immune–stromal landscape of PVTT, uncover NID1-driven stromal remodeling as a mechanism of immune evasion, and highlight drug repurposing as an immediately actionable strategy to improve outcomes in HCC with PVTT.

Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates formed by lymphocytes and antigen-presenting cells within chronic inflammatory microenvironments or tumor microenvironments (TMEs), and their initiation phase is a critical step for mounting an effective antitumor immune response. TLS initiation depends on the interplay between lymphoid tissue inducer cells and lymphoid tissue organizer cells and is finely regulated by multiple cytokines and chemokines. This review systematically summarizes the key triggers and signaling networks driving TLS initiation, elucidating how TLSs reshape the TMEs, facilitate antigen presentation, and recruit immune cells to enhance antitumor immune responses. Furthermore, potential strategies to modulate TLS initiation are discussed, along with the emerging role of TLSs as promising targets in cancer immunotherapy.

Leveraging living materials such as algae as sustainable photocatalytic platform is highly promising for mitigating antibiotic water pollution; however, they are confronted with low catalytic efficiency and difficulty in recovery, as imposed by their passive, static working mode. Herein, we report a Janus microgel robot (JMR) that features the integration of magnetic-controlled mobility and living photocatalytic function, allowing for substantially boosting antibiotic degradation efficiency and efficient recovery in an actively magnetic-controlled manner. The key to the JMR lies in harnessing gas shear microfluidic technique to manipulate the spatial distribution of TiO₂–Chlorella pyrenoidosa and Fe₃O₄ phases into a Janus architecture, followed by gel encapsulation to prevent cell leakage. Under simulated sunlight, the JMR system achieves 77% antibiotic degradation within 10 h, which is 10 times that of the free C. pyrenoidosa (7.6%). Moreover, we demonstrate that the JMR can be imparted with enhanced degradation efficiency by 10.6% and over 95% effectiveness through 3 consecutive operational cycles in actively magnetic-controlled mode. This work establishes a prototype for sustainable environmental biorobots and provides a novel strategy for photocatalytic-biological hybrid system design, advancing the next-generation living materials for water treatment.

Liposome-in-liposome systems with multicompartment structures offer advantages in structural complexity and functional programmability, but their application is limited by poor controllability in conventional fabrication. A recent Nature Chemistry study by Elani et al. reports a methodology to prepare sub-200-nm dual-layered liposomes, enabling customizable bilayers and adjustable interbilayer spaces. Their stepwise assembly approach promises to facilitate the integration of artificial intelligence expertise from unilamellar liposome research into liposome-in-liposome systems, thereby further optimizing formulations and enabling biological predictions. Consequently, this advancement may accelerate the clinical translation of liposomal drugs and advance frontier research in areas such as artificial organelles and lipid nanoparticles.

The efficient utilization of near-infrared (NIR) light remains a paramount challenge for solar-driven photocatalytic nitrogen fixation, primarily due to rapid energy dissipation of hot carriers via phonon scattering. Here, we construct a well-defined core–shell heterostructure through the in situ anchoring of an ultrathin, sulfur-vacancy-rich GeS_x shell onto gold nanorods (AuNRs)—an atomic-scale configuration that fundamentally suppresses phonon-mediated energy loss. This suppression, directly evidenced by transient absorption spectroscopy through reduced phonon frequency and scattering rate, prolongs the lifetime of plasmon-derived hot electrons. Combined with the vacancy-enabled activation of the robust N≡N bond at exposed Ge sites, this catalyst achieves an exceptional NH₃ production rate of 1,225.6 μmol g⁻¹ h⁻¹ under NIR irradiation and a remarkable apparent quantum efficiency of 1.23% at 880 nm—a performance that rivals many ultraviolet/visible-driven systems. Through in situ spectroscopy, transient absorption studies, and theoretical analysis, we elucidate the atomic-level origin of synergistic catalysis: the GeS_x shell not only suppresses phonon scattering by reducing phonon frequency and velocity, but also creates electron-deficient Ge sites that function as preferential centers for N₂ adsorption and activation, thereby bridging hot-carrier dynamics with molecular reduction kinetics. This work provides a definitive strategy for overcoming fundamental energy loss limitations in plasmonic photocatalysis by concurrently engineering the energy dissipation pathway and the atomic catalytic environment.

Present high-voltage Li-ion aqueous batteries largely rely on highly concentrated (up to 63 m) “water-in-salt” electrolyte with limited cycle life (<1,000 cycles) and little hope in practical application. To date, no dilute aqueous electrolyte (salt molality < 2 m) can reliably operate beyond 2 V with cycling life over 1,000 cycles. Here, we introduce a “methanesulfonate in phosphate” superstructure that simultaneously tailors Li⁺ migration in molecular crowding solvent and electrode surfaces, which enables an unprecedented electrochemical stability window (up to 4.5 V) and cyclability (up to 10,000 cycles) in a dilute 1.1-m aqueous electrolyte. In addition, Such methanesulfonate in phosphate electrolyte can be also applied in various high-voltage electrode couples, and the assembled 60-V, 15-A·h LiMn₂O₄/LiTi₂(PO₄)₃ aqueous battery can drive an electric bike for 70 km, highlighting the power of such electrolyte design in the commercialization of high-voltage aqueous batteries.

T7 RNA polymerase (T7 RNAP) is the most widely used enzyme for synthesizing therapeutic mRNA. However, RNA transcribed by T7 RNAP often contains double-stranded RNA (dsRNA) by-products that trigger innate immune responses and complicate purification. Here, we report an engineered T7 RNAP variant, M30, which exhibits higher catalytic efficiency and reduced dsRNA by-product formation. M30 was developed through 4 rounds of directed evolution using an ultrahigh-throughput aptamer-based fluorescence-activated droplet sorting system. M30 displays a 10-fold increase in catalytic efficiency over wild-type T7 RNAP at 37 °C, along with markedly enhanced thermostability and approximately 10-fold lower production of dsRNA by-products. mRNAs synthesized with M30 achieve efficient protein expression in human cells and in mice, while eliciting reduced immunogenicity compared with mRNAs produced by wild-type T7 RNAP. Biophysical assays and structural analyses suggest that these improvements result from increased DNA template binding affinity and decreased RNA binding affinity. Together, these features make M30 a promising catalyst for high-quality therapeutic mRNA production.