The ANK2 gene mutations are marked risk factors for autism spectrum disorder, one of the neurodevelopmental disorders (NDDs) that often extends into adulthood and has a complex etiology involving genetic and environmental factors. ANK2 encodes 2 major isoforms, AnkB-220 (220-kDa isoform of ankyrin-B) and giant AnkB-440. We previously generated a targeted knockout (KO) of giant AnkB-440 in 2 cynomolgus and 2 rhesus monkeys. While no autism-spectrum-disorder-like phenotypes were observed during infancy, we found marked brain volume loss. In this study, we conducted a longitudinal multimodal study in these giant ANK2 KO monkeys during adolescent and young adulthood. Behavioral results from these giant ANK2 KO monkeys revealed increased locomotor activity, deficient cognition (including working memory, cognitive flexibility, and operant lever-press learning), and impaired emotional regulation and social interaction. Furthermore, the giant ANK2 KO monkeys exhibited persistent structural and functional brain abnormalities, up-regulation of brain triglyceride and glycerophospholipids, and peripheral blood transcriptome signatures of immune dysregulation, which may be related to their behavioral alternations. These observations suggest that giant ANK2 depletion in non-human primates phenocopies aspects of behavioral, neural, and molecular features characteristic of NDDs. This study provides an in-depth exploratory longitudinal characterization of giant ANK2 functions in primate brains, which may contribute to translational research on NDDs.

Addressing uranium contamination in tailings wastewater is key to reducing ecological threats and securing the future of nuclear power. The integration of adsorption with in situ photocatalytic U(VI) immobilization has been explored as a green alternative, but charge separation inefficiency and poor ion selectivity continue to hinder its use in complex wastewater. Herein, we constructed a bimetallic metal–organic framework, OVs-Zr/Fe UiO-66-NH₂, by incorporating Fe²⁺/Fe³⁺ species into the UiO-66-NH₂ lattice. The incorporation of Fe into the UiO-66-NH₂ lattice narrows the bandgap and improves visible-light absorption. The same Fe doping induces oxygen vacancies (OVs) within the framework. The OVs trap photogenerated electrons to enhance charge separation, while their electron-rich nature favors the selective uptake of UO₂²⁺. Meanwhile, the Fe²⁺/Fe³⁺ redox couple provides an internal electron mediation pathway, directing electrons to the OV-bound uranyl species and promoting the interfacial uranium conversion into stable species. With this combined adsorption–photocatalysis mechanism, OVs-Zr/Fe UiO-66-NH₂ removed 99.2% of U(VI) within 6 h under ambient air without sacrificial agents, and its distribution coefficient (K_d) reached 1.96 × 10⁵ ml g⁻¹, 11.9 times that of pristine UiO-66-NH₂. This work provides a synergistic strategy for crafting photocatalysts with high efficiency and selectivity for sustainable uranium remediation in complex waters.

Circadian disruption and metabolic dysfunction are linked to chronic disease, but whether circadian syndrome, which combines metabolic, sleep, and mood traits, relates to overall and site-specific cancer risk remains unclear. We prospectively studied 367,832 cancer-free participants in the UK Biobank, of whom 82,547 (22.4%) had circadian syndrome, defined by at least 4 of 7 features: abdominal obesity, high triglycerides, low levels of high-density lipoprotein cholesterol, high blood pressure, impaired glucose regulation, short sleep, and depression. Associations with overall cancer and 23 site-specific cancers were evaluated using Cox proportional-hazards and competing-risk models, with additional dose–response, biomarker, and population-burden analyses. During follow-up, 47,695 participants developed cancer. Circadian syndrome was associated with a higher incidence of overall cancer (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.10 to 1.14). The strongest positive associations were observed for endometrial cancer (HR, 1.88; 95% CI, 1.71 to 2.08), liver cancer (HR, 1.67; 95% CI, 1.47 to 1.89), and kidney cancer (HR, 1.55; 95% CI, 1.41 to 1.70). Findings remained similar after accounting for death from other causes and across sensitivity analyses, whereas inverse associations for prostate and brain cancers were exploratory. Sex-hormone-binding globulin statistically accounted for 51.0% of the endometrial cancer association, and C-reactive protein accounted for 26.4% of the overall cancer association. The highest population-attributable fractions were estimated for endometrial (13.5%) and liver cancers (13.4%). Circadian syndrome may help identify populations at increased cancer risk and inform prevention strategies integrating circadian and metabolic health.

Rhythm perception enables humans to navigate dynamic environments. The auditory system is particularly adept at processing rhythmic temporal structure, and auditory training exerts a greater influence than visual training on visual rhythm perception, leading to the hypothesis that auditory coding may support visual rhythm representation. This raises a fundamental question: whether and to what extent the deprivation of auditory coding capabilities influences visual rhythm processing. To investigate this issue, we assessed cortical tracking of hierarchical visual rhythms in hearing and early deaf participants using electroencephalography (EEG). Participants viewed 2 types of rhythmic sequences: geometric shapes and point-light walkers. Each stimulus type consists of a lower-order basic rhythm defined by stimulus recurrence and a higher-order chunk rhythm built on perceptual or cognitive organization. Results showed that hearing participants exhibited robust cortical tracking of both basic and chunk rhythms across stimuli. In contrast, deaf participants exhibited preserved tracking of basic rhythms but reduced tracking of chunk rhythms. Moreover, compared with the hearing group, the deaf group showed reduced visual–auditory and visual–frontal functional connectivity, and individual differences in connectivity strength were positively correlated with chunk-rhythm tracking. These findings support a hierarchical auditory scaffolding framework, in which auditory experience is selectively associated with higher-order visual rhythm perception through temporal chunking mechanisms.

Breast cancer metastasis reflects both tumor cell heterogeneity and compatibility with distant organ microenvironments. Tumor-resident bacteria add a potential nongenetic layer to this process, but the strength of evidence varies substantially across proposed mechanisms. Here, we introduce the concept of a “bacterial passenger”, which is operationally defined as a viable bacterium localized within, rather than merely adherent to, a tumor cell or circulating tumor cell during dissemination. Passenger status must be distinguished from nonviable microbial DNA, extracellular signals, and environmental or reagent contamination through viability-aware imaging, culture or functional assays, and matched strain-level evidence across primary tumors, circulating tumor cells, and metastases. The term describes physical codissemination and does not itself imply a causal effect. Breast cancer models show that intracellular bacteria can increase survival under fluid shear stress and metastatic colonization, yet direct evidence that they determine organ tropism, brain metastasis, or treatment resistance remains limited. We therefore present the seed–soil–passenger triad as a bacteria-centered, falsifiable extension of the seed–soil framework rather than a replacement. Its value lies in testable predictions about codissemination, organ-dependent effects, and stage-specific bacterial perturbation, coupled to rigorous low-biomass controls. Fungi and viruses are outside the present operational framework because comparable evidence for viable codissemination with breast cancer cells is not available.

How fibroblast heterogeneity orchestrates tissue regeneration by remodeling tissue mechanical properties that guide stem cell function is not well understood. Although fibroblasts are increasingly recognized as key regulators of tissue homeostasis, the specific subpopulations and molecular pathways through which they remodel the mechanical niche during hair follicle regeneration are not fully defined. Here, we identify that Hmmr⁺ fibroblasts located beneath the dermal papilla (DP) of the hair follicle promote hair follicle regeneration by secreting extracellular matrix (ECM) components to activate hair follicle stem cells. Single-cell RNA-sequencing and immunostaining mapped spatially distinct fibroblast subpopulations in the dermal microenvironment and showed that regional ECM viscoelastic remodeling occurs prior to hair regeneration and coincides precisely with the emergence of Hmmr⁺ fibroblasts. Functional studies in vivo and in skin organoids demonstrate that Hmmr⁺ fibroblasts act as mechanical sensors that engage DP cells via NCAM1–FGFR1 signaling to stimulate hair regeneration. We propose a tripartite biomechanical module comprising ECM viscoelastic remodeling (effector), Hmmr⁺ fibroblasts (sensor), and DP cells (executor) that cooperatively drives hair regeneration. Together, our work identifies a heterogeneous fibroblast-defined mechanical niche as a central regulator of tissue renewal, highlighting the role of fibroblast diversity in coordinating regeneration and advancing our understanding of the mechano-molecular basis of tissue repair.

The hypoxic microenvironment in gliomas critically contributes to malignant progression. This study investigates the functional role and molecular mechanisms of long noncoding RNAs derived from hypoxic endothelial cell exosomes in reprogramming tumor-associated macrophages and driving glioma progression. We identified a novel long noncoding RNA, lnc-DKK3, enriched in exosomes secreted by hypoxic endothelial cells. Nuclear-localized lnc-DKK3 suppresses PD-L1 ubiquitination in macrophages by binding to USP47, promoting M2-like polarization and immunosuppression. Additionally, the lnc-DKK3/USP47 axis stabilizes RelA, augmenting its transcriptional activity and collectively accelerating glioma progression. Thus, hypoxic endothelial-cell-derived lnc-DKK3 drives M2 polarization via the USP47/PD-L1 pathway and promotes glioma progression via the USP47/RelA axis, highlighting its therapeutic potential. To translate these insights, we developed a macrophage-specific CRISPR interference–liquid nanoparticle platform targeting the lnc-DKK3 super-enhancer and demonstrated its synergistic sensitization to anti-PD-1 therapy in preclinical models.

Developing high-performance and high-safety lithium-metal batteries (LMBs) is of importance to meet the growing demands of next-generation energy storage. Leveraging the high structural tunability and chemical versatility of polymer materials, rational design strategies for advanced polymer separators and solid polymer electrolytes have attracted considerable attention, showing great promise for enabling LMBs with enhanced safety and reliability. This review summarizes previously reported design strategies for these key components, highlighting how molecular and microstructural engineering of polymers can address core challenges such as lithium dendrite growth and thermal instability. Recent advancements on the polymer design strategies were systematically analyzed with an emphasis on the underlying mechanisms in regulating ion transport, suppressing dendrite growth, and enhancing operation safety. Finally, current challenges and future perspectives are discussed, which aim at deepening the insight into rational design of polymer separators and solid polymer electrolyte toward further advancement and practical applications of LMBs.

Adoptive natural killer (NK) cell therapy represents a promising strategy for triple-negative breast cancer, but its therapeutic efficacy is often limited by poor intratumoral persistence and functional exhaustion within the immunosuppressive tumor microenvironment. Here, we developed an injectable DNA supramolecular hydrogel-based NK cell delivery platform (NK@DSH) that functions as a protective reservoir for transferred NK cells. The DNA supramolecular hydrogel enabled efficient NK cell encapsulation under mild conditions while preserving both cell viability and functionality. In vivo fluorescence tracking demonstrated prolonged intratumoral persistence of NK cells for up to 7 d and increased NK cell accumulation within tumor tissues. In a 4T1 tumor-bearing mouse model, NK@DSH produced stronger tumor growth inhibition than free NK cell administration while showing negligible systemic toxicity. This DSH-based strategy provides a generalizable platform for adoptive cell therapy, offering new insights into overcoming cell-persistence barriers in the treatment of solid tumors.

Adolescent sleep deprivation (SD) increases latent vulnerability to pain, a major risk factor for persistent postsurgical pain (PPSP) in adulthood, yet the underlying mechanisms remain unclear. Given the limitations of current pharmacological treatments, noninvasive transcranial focused ultrasound (TFUS) offers a promising neuromodulatory alternative; however, its therapeutic efficacy for PPSP remains unknown. Here, we utilized a mouse model of adolescent SD followed by an adult plantar incision to elucidate how early sleep loss drives long-term PPSP and to systematically investigate the therapeutic potential and underlying mechanisms of TFUS. By integrating resting-state functional magnetic resonance imaging, chemogenetics, and behavioral assays, we demonstrated that medial prefrontal cortex glutamatergic (mPFC^Glu) hypoactivity mediates this SD-driven PPSP development. To evaluate TFUS intervention, we first screened various stimulation paradigms and identified that 200-Hz pulse repetition frequency TFUS optimally activated mPFC^Glu neurons and effectively alleviated PPSP. Mechanistically, guided by single-nucleus RNA sequencing, we found that TFUS activates the mechanosensitive transient receptor potential channel 5 (TRPC5) to promote Homer1-dependent glutamatergic synaptic plasticity. This molecular cascade subsequently ameliorates mPFC^Glu hypoactivity and normalizes aberrant network-level gamma oscillations and spike–gamma phase locking. Collectively, our findings suggest that adolescent SD precipitates adult PPSP via mPFC^Glu dysfunction and that TFUS alleviates this condition through an integrated pathway linking molecular mechanosensation to network rhythm recovery. These results offer a novel therapeutic paradigm and provide a mechanistic foundation for developing noninvasive TFUS strategies to manage PPSP in vulnerable patients.