The elemental composition of brains changes progressively with age, yet these metallome alterations remain largely unexplored as diagnostic biomarkers in neurological disease. Here, we present a comprehensive analysis of 24 inorganic elements in paired cerebrospinal fluid and serum samples from 1,608 individuals spanning healthy aging through 14 neurological conditions, representing the largest systematically standardized cohort for neurological metallomics. Uniquely, our unselected, consecutively admitted clinical cohort captures the full heterogeneity of neurological presentations, overcoming the limitations of traditional case–control designs focused on isolated disease entities. Machine learning analysis reveals that aging is associated with distinct cerebrospinal fluid elemental signatures independent of peripheral blood changes, primarily reflecting blood–brain barrier permeability alterations that correlate with established albumin quotient measurements. We identify 2 predominant patterns of neurological elemental dysregulation: one mainly consistent with passive barrier-mediated leakage in inflammatory conditions, and another mainly indicative of disease-intrinsic perturbations of metal homeostasis in neurodegenerative disorders. Age-stratified analysis reveals that elemental signatures evolve differently across the lifespan for distinct pathological processes. The integration of elemental signatures with routine clinical parameters through ensemble learning approaches enhances diagnostic accuracy across all tested neurological categories, establishing metallomics as a complementary biomarker class that captures orthogonal pathophysiological information. These findings establish brain metallomics as an emerging field where artificial intelligence reveals complex multi-element interactions present in neurological aging, opening new avenues for precision medicine in age-related neurological disorders.

Bioelectronic patches have emerged as promising tools for localized and precise intracellular delivery. However, their application is limited by poor conformability and suboptimal delivery efficiency on anatomically complex organs. A recent study published in Cell introduced POCKET, a kirigami-based electrotransfection bioelectronic patch for conformable intracellular delivery on complex organ surfaces. This study establishes a universal conformality framework for maximizing organ coverage. POCKET connects nanopores to target cells, enhancing electroporation and transmembrane transport for efficient drug delivery to organs. By integrating mechanical conformality with interfacial bioelectronics, this platform enhances spatial precision and therapeutic efficacy in complex organs, promising advances in gene therapy, organ protection, and regenerative medicine.

The function of ganglioside oligosaccharides critically depends on the number, linkage, and spatial arrangement of sialic acid residues, yet direct discrimination of highly sialylated ganglioside oligosaccharides, particularly at the isomeric level, remains challenging due to their high charge density and subtle structural differences. Here, we present a nanopore-based strategy for single-molecule identification of ganglioside oligosaccharides. By engineering the sensing region of an α-hemolysin nanopore with synergistic cationic and aromatic mutations, we markedly enhance the capture of multisialylated glycans and prolong their residence within the pore. This interaction-mediated slowdown converts otherwise transient blockade events into extended trajectories containing rich molecular dynamics information. Beyond conventional blockade amplitude and dwell time descriptors, we introduce time- and spectral-domain features to characterize intraevent current fluctuations, thereby overcoming the key limitations of traditional nanopore analyses. Using this approach, we reliably discriminate 4 linkage isomers of trisialylated ganglioside glycans and accurately identify ganglioside oligosaccharides containing 3 to 5 sialic acid residues in heterogeneous mixtures. When combined with a machine-learning framework, the extracted time- and spectral-domain features enable single-level isomer identification and mixture deconvolution and remain effective even in complex biological matrices such as neural cell line and brain tissue lysates. Together, these results demonstrate that controlling analyte–pore interactions to unlock higher-order dynamical signatures enables nanopore analysis of highly sialylated ganglioside oligosaccharides, providing a general strategy for single-molecule glycan sequence elucidation in biologically relevant environments.

Lipid accumulation drives the development of atherosclerotic cardiovascular disease, the leading cause of death worldwide. The liver is the primary target for lipid-lowering therapies due to its central role in lipid metabolism. Despite advances in small-molecule drugs, substantial residual cardiovascular risk remains. Recent clinical evidence in 2026 reaffirms the “lower is better” paradigm, showing that achieving very low low-density lipoprotein cholesterol (<55 mg/dl) improves outcomes versus standard goals (<70 mg/dl). RNA-targeted therapeutics, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), offer a transformative approach by durably silencing genetically validated lipid targets. Conjugation to N-acetylgalactosamine (GalNAc) enables hepatocyte-specific delivery. Examples include inclisiran (targeting proprotein convertase subtilisin/kexin type 9 [PCSK9]) and agents against apolipoprotein C-III (APOC3), lipoprotein(a) [Lp(a)], and angiopoietin-like protein 3 (ANGPTL3). Beyond protein-coding messenger RNAs (mRNAs), RNA therapeutics can also target noncoding RNAs (microRNAs and long noncoding RNAs) that regulate cholesterol homeostasis. Additionally, mRNA lipid nanoparticle-based in vivo base editing (e.g., VERVE 101/102 targeting PCSK9) has entered clinical trials, offering potential for permanent genetic correction with a single infusion. In the future, RNA-targeted therapeutics may expand beyond hepatic lipid modulation to directly target vascular lipid metabolism and plaque biology. Advances in extrahepatic delivery and rational combination regimens could transform RNA therapy from transient lipid-lowering to long-term, disease-modifying interventions. The recent 2026 American College of Cardiology/American Heart Association dyslipidemia guideline emphasizes the clinical importance of targeting PCSK9, APOC3, Lp(a), and ANGPTL3. This review provides a state-of-the-art overview of RNA-targeted therapeutics in hyperlipidemia and discusses future research directions in this emerging field.

Cellulose, the most abundant natural polymer, is a promising platform for sustainable bioplastics. However, cellulose-based bioplastics derived from macrofibers or nanocellulose still fall short of petrochemical plastics in thermal stability, mechanical performance, and processability. In this work, we systematically examine molecular-scale design strategies to bridge the gap between material properties and processing behavior, including supramolecular network reconstruction, dynamic dissipative systems, and programmable architectures. These approaches enable cellulose bioplastics with improved formability, thermal resistance, mechanical strength, and programmable responsiveness, thereby expanding their potential in aerospace, intelligent construction, high-end protective equipment, and biomedicine. Finally, we outline future research directions to accelerate the development of cellulose-based materials toward high-performance, recyclable, intelligent, and environmentally friendly applications.

Fusion oncogenes are among the most potent and clinically actionable cancer drivers, contributing to approximately 15% to 20% of human malignancies. Traditionally viewed as stable consequences of chromosomal translocations, fusion oncogenesis has long been interpreted through a DNA-centric paradigm. However, this view is now challenged by the discovery of a vast and dynamic landscape of fusion RNAs. Recent integrative genomic studies suggest that extrachromosomal DNA (ecDNA) can serve as a platform for the formation, diversification, and amplification of oncogenic fusion transcripts in multiple cancer contexts. Here, we propose the “ecDNA fusion factory” as a unifying conceptual framework that integrates nonchromosomal genome architecture, structural instability, and RNA-level regulatory consequences to expand current understanding about the origin and adaptive evolution of some fusion drivers. In this model, fusion output can be dynamic and heterogeneous, shaped by ecDNA copy-number flux and context-dependent structural remodeling rather than exclusively by a single, fixed chromosomal breakpoint. This reframing suggests distinct therapeutic vulnerabilities, potentially motivating strategies that target both the fusion oncoprotein and the ecDNA platform that sustains it, and necessitates a revision of diagnostic paradigms to detect these structurally plastic and dynamically evolving oncogenic elements. Together, this perspective broadens current models of fusion-driven oncogenesis and highlights possible implications for precision oncology.

The detection and identification of low-frequency underwater sounds remain challenging due to inefficient acoustic–mechanical–electrical coupling, which limits the conversion of low-frequency weak pressure fluctuations into stable electrical signals in conventional hydrophones. Here, we develop a capacitive hydrogel acoustic sensor (CHAS) that enhances low-frequency transduction through a micro-pyramid iontronic structure governed by dynamic electric double layer (EDL) effects. By combining the EDL-based sensing mechanism with a phase-sensitive lock-in amplification circuit providing a 40 dB gain, the system preserves weak acoustic information within the 20 to 1,000 Hz range. The sensor achieves an average sensitivity of −158.86 dB and reliably detects diverse low-frequency underwater acoustic events, including human speech, water impacts, and vessel-radiated noise. A neural network trained on the ShipsEar database yields 96.3% accuracy and, especially, maintains 89.1% accuracy when directly applied to CHAS-acquired signals without retraining, demonstrating that the iontronic sensing mechanism preserves physically meaningful acoustic features and enables reliable cross-domain intelligent analysis. This work establishes an integrated sensing framework that links iontronic device physics, circuit-level signal conditioning, and data-driven acoustic interpretation, providing a practical pathway toward intelligent low-frequency underwater acoustic monitoring and target recognition.

Platelets are traditionally recognized for their roles in hemostasis, but their involvement as active immune modulators in cutaneous neuroimmune signaling remains poorly understood. In this study, we integrated multi-modal genetic and pharmacological strategies to investigate the functional contribution of platelets to skin inflammation and chronic itch. Optogenetic activation of platelets was sufficient to elicit localized skin inflammation, erythema, and robust pruritus, with transcriptomic profiling of lesions showing strong concordance with the clinical signatures of atopic dermatitis (AD). In experimental AD models, platelet depletion markedly reduced scratching behavior, inflammatory cell infiltration, and C-fiber excitability, whereas platelet activation exacerbated these phenotypes. Mechanistically, activated platelets release serotonin [5-hydroxytryptamine (5-HT)], which compromises vascular integrity and facilitates platelet extravasation into the dermis. This “neuroimmune hub” promotes macrophage recruitment and sensitizes TRPV1⁺ pruriceptors. Transcriptomic analysis revealed that platelet-derived 5-HT drives these processes via HTR2B and HTR7 signaling. Specifically, genetic ablation of HTR2B in TRPV1⁺ neurons selectively impaired itch transmission. Furthermore, re-analysis of clinical datasets confirmed the enrichment of HTR2B and HTR7 in skin macrophage populations during inflammation. Systemic administration of HTR antagonists or the anti-platelet agent clopidogrel markedly attenuated both inflammation and pruritus across multiple models. Our findings identify the platelet–immune–neuron axis as a key driver of cutaneous dysfunction and a promising therapeutic target for chronic inflammatory skin disorders.

Although predatory behaviors are evolutionarily conserved, they can be enhanced through experience-dependent plasticity. While vibrissal somatosensation is recognized as a key mediator of hunting behavior, the mechanism underlying vibrissal somatosensory-mediated predatory hunting learning remains not yet well understood. In this study, we report that vibrissal tactile input plays an essential role in hunting learning. Activation of the vGlut1⁺ S1BF–SC pathway is sufficient to evoke predatory hunting, while its inactivation abolished practice-induced behavioral improvements. SC-projecting vGlut1⁺ S1BF neurons exhibited robust responses to whisker mechanosensory stimulation. Furthermore, hunting training selectively enhanced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptormediated excitatory transmission in the vGlut1⁺ S1BF–SC pathway. Together, these data reveal the corticotectal neural circuit from the primary somatosensory cortex to superior colliculus that was specifically engaged in vibrissal somatosensory-mediated hunting learning by strengthening synaptic connections.

Acute-phase neuroinflammation and early brain injury progressing rapidly is responsible for substantial severity and mortality in subarachnoid hemorrhage (SAH). While cohort studies have confirmed that aerobic exercise (AE) was associated with decreased short-term mortality, its precise mechanisms remain elusive. We employed a murine SAH model subjected to preconditioning AE to validate the above hypothesis, combining early neurological function assessment and histological staining. Whole-transcriptome profiling and single-cell RNA sequencing were performed to capture differentially expressed genes and to delineate subtype-specific differentiation. To recapitulate the neuroimmune crosstalk in vitro, we established a primary neutrophil–microglia coculture system. Targeted receptor–ligand interaction studies were employed to validate the specific environmental variables driving their synergistic activation. Our data indicated that AE significantly ameliorated neurological outcomes, cerebral edema, and neuronal apoptosis post-SAH. Sequencing data identified classical pro-inflammatory M1-like microglia, alongside a novel early-response microglial subset characterized by high expression of transforming growth factor beta 1; both populations were regulated by AE for modulating neuroinflammation and significantly correlated with infiltrating neutrophil counts. This crosstalk was mediated by mature neutrophil-derived leucine-rich alpha-2-glycoprotein 1 (Lrg1), which differentially activated the microglial transforming growth factor beta signaling pathway. Collectively, AE-mediated suppression of neutrophil infiltration rebalanced microglial differentiation, thereby attenuating neuroinflammation following SAH. We identified Lrg1 as a key immune mediator in this process, highlighting exercise-induced reprogramming at the receptor level as a potential therapeutic strategy for SAH.