Achieving spatially resolved chemical functionalization on graphene lattices is essential for fabricating advanced two-dimensional (2D) architectures. However, current covalent patterning strategies struggle to simultaneously minimize energy input for lattice preservation and offer the chemical versatility required for fine-tuning the local doping state of the 2D lattice. Here, a modular diaryl-sulfonium platform is developed for the ultra-low-threshold covalent patterning of monolayer graphene, further enabling substituent-encoded pattern of local work-function. Driven by a highly efficient, graphene-mediated hot-electron single-electron transfer (SET) mechanism, this approach lowers activation barriers, enabling non-destructive patterning with laser powers as low as 0.10 mW and irradiation time of a few seconds-orders of magnitude lower than conventional photon-driven processes-thereby ensuring high pattern fidelity without thermal degradation. By incorporating a library of six chemically distinct σ-bound substituents (including phenyl, fluorophenyl, trifluoroethyl, vinyl, phenylthiophenyl, and bromoethyl) onto a unified sulfonium scaffold, precise control over local work-function can be achieved. Kelvin Probe Force Microscopy (KPFM) reveals a continuous, chemically tunable spectrum of surface potential shifts (ΔCPD from ∼30 to ∼300 mV). Combined with exceptional ambient stability and thermal erasability, this work offers a robust, energy-efficient paradigm for chemically encoding reconfigurable 2D electronic landscapes.
Biological barriers remain a primary limitation to effective cancer therapy, restricting drug delivery, distribution, and therapeutic efficacy across tumor sites. These barriers arise from a complex and dynamic interplay between tumor- and host-derived factors, including abnormal vasculature, dense extracellular matrices, immune clearance, and spatiotemporal heterogeneity within the tumor microenvironment. Increasing evidence suggests that these components operate as an integrated and adaptive network. Here, we conceptualize this network as "tumor systemic intelligence," which enables tumors to sense and respond to therapeutic and physiological perturbations by reinforcing delivery barriers and limiting drug access. Conventional nanomedicine strategies, often designed to overcome individual barriers, have shown limited success in addressing this coordinated system. To overcome these limitations, we propose "adaptive intelligence" as a design paradigm for next-generation nanocarriers. In this framework, nanocarriers are engineered as responsive systems capable of sensing microenvironmental cues and dynamically modulating their physicochemical properties to navigate multiple, evolving barriers during systemic circulation and tumor penetration. We discuss key design strategies for adaptive nanocarriers, including programmable control over size, shape, surface charge, and bioactive interfaces, enabling improved circulation stability, enhanced transvascular transport, deeper tumor penetration, and reduced immune recognition. We further examine how these systems can modulate or bypass critical barriers such as extracellular matrix density, abnormal perfusion, and cellular uptake limitations. Integration with external physical stimuli is also considered to further enhance barrier penetration and delivery efficiency. Despite promising advances, clinical translation remains limited by challenges including nanocarrier safety, immunogenicity, and the complexity of tumor-host interactions. This review highlights emerging opportunities and design principles for adaptive nanocarriers that effectively navigate biological barriers, with the goal of improving drug delivery and therapeutic outcomes in cancer treatment. Importantly, the concepts of systemic intelligence and adaptive intelligence are intended as conceptual frameworks to guide the rational design of next-generation nanomedicines rather than as formal biological classifications.
To bypass the enduring limitations intrinsic to traditional size-sieving separation, alternative materials for CO2/H2 separation need to be developed. Here, we program a permeation inversion in CO2/H2 transport by constructing a nanoconfined ionic liquid membrane through the synergistic engineering of graphene oxide nanosheets and ionic liquids. A substrate-assisted size-selection strategy enables the preferential incorporation of large nanosheets, which form ordered laminates, while short-chain CO2-philic ionic liquids are precisely confined within the interlayer galleries. The resulting membrane exhibits inverted transport behavior, achieving an ultrahigh CO2 permeance of 358.2 GPU and a mixed-gas CO2/H2 selectivity of 201.9 under a 10:90 CO2/H2 feed─surpassing the upper bounds of conventional polymeric and mixed-matrix membranes. Scalability is demonstrated using a five-cell module, in which CO2 flux increases linearly without selectivity loss. Molecular dynamics simulations and spectroscopic studies reveal that the nanoconfined ionic liquid phase creates a continuous, high-solubility pathway for CO2, whereas H2 is largely excluded from the graphene oxide interfaces. This study establishes nanosheet-ionic liquid synergy as a programmable design platform to engineer permeation inversion, offering a scalable route to advanced CO2/H2 separation membranes.
Depression carries the highest burden of mental health-related disability in the United States. Approximately 13% of military veterans report elevated rates of depression. Despite the availability of evidence-based treatments for depression, nearly 50% of veterans in need of mental health care remain untreated. Internet-based interventions show promise in reducing this gap; however, there are currently no standard self-guided internet-based interventions for depressive symptoms in veterans. Deprexis is one such intervention that leverages cognitive behavioral therapy to target depressive symptoms. This pilot study evaluated the feasibility, acceptability, and preliminary effectiveness of Deprexis, a fully self-guided internet-based intervention for depression, in US military veterans with mild to severe depressive symptoms. This open-label pilot trial recruited 19 veterans with mild to severe depression (mean age 55.5, SD 8.2 y; baseline Quick Inventory of Depressive Symptomatology-Self-Report [QIDS-SR]: mean 16.2, SD 4.1) for an 8-week course of Deprexis, with self-report assessments at baseline, posttreatment (8 wk), and follow-up (16 wk). Primary outcomes included depressive symptoms (QIDS-SR), functional disability (World Health Organization Disability Assessment Schedule 2.0), and symptom-related disability (Sheehan Disability Scale). Feasibility was assessed through recruitment and retention rates, and acceptability was measured using validated questionnaires (Credibility and Expectancy Questionnaire and Client Satisfaction Questionnaire). Multilevel models examined change over time, with effect sizes calculated using pooled SDs from unconditional models. Recruitment and retention targets were met, with 15 out of 19 (79%) participants meeting the adherence criteria (ie, ≥60 min of active program use). Of these, 14 participants completed posttreatment questionnaires and were included in the completer analyses. The program received a positive acceptability rating: of the 18 participants who completed follow-up assessments, 78% (n=14) rated services as good or excellent and 72% (n=13) were satisfied with the amount of help received. No safety concerns were reported. Among completers (n=14), QIDS-SR scores decreased from baseline to posttreatment (estimate -2.22, SE 1.44; P=.14; d=-0.54, 95% CI -1.07 to 0.13) and follow-up (estimate -2.85, SE 1.19; P=.02; d=-0.70, 95% CI -1.21 to -0.08) with moderate-to-large effect sizes. Effect sizes were similar in the total sample. Functioning (World Health Organization Disability Assessment Schedule 2.0) improved among completers at follow-up (estimate -8.09, SE 3.80; P=.045; d=-0.41, 95% CI -0.96 to -0.05). Disability (Sheehan Disability Scale) did not significantly improve from baseline to posttreatment or follow-up. This pilot trial demonstrates that Deprexis is feasible and acceptable for veterans with mild to severe depression, with preliminary evidence of effectiveness for depressive symptoms. The delayed emergence of functional improvements and sustained gains at follow-up support the potential of this scalable intervention. The results provide a strong foundation for the ongoing randomized controlled trial.
Generative artificial intelligence (AI) is now widely applied in medicinal chemistry, with detailed case studies emerging in the literature. Here, we describe an early application of REINVENT, AstraZeneca's in-house generative molecular design platform, to identify new inhibitor scaffolds for hematopoietic progenitor kinase 1 (HPK1). REINVENT was deployed at two stages of the project to address distinct design objectives. For hit identification, transfer learning on kinase-active compounds, followed by reinforcement learning guided by QSAR-based scoring, led to the discovery of three active chemotypes. Subsequently, REINVENT was applied to scaffold hopping, using 3D pharmacophore and docking models as scoring functions, which enabled the identification of two additional active chemotypes. Optimization of one of these scaffolds delivered a compound with potent cellular activity, kinase selectivity, and favorable rat pharmacokinetics. These results demonstrate the value of integrating generative AI with medicinal chemistry expertise and support broader application of the approach in future discovery programs.
Rosa roxburghii Tratt. is a high-elevation fruit shrub with strong ultraviolet-B (UV-B) tolerance, and plant sterols are critical for its UV-B adaptation, but their regulatory mechanisms remain unknown. Here, we identified a key oxidosqualene cyclase gene, RrOSC5, which encodes a functional cycloartenol synthase and is dynamically upregulated under UV-B stress. Overexpression of RrOSC5 enhanced sterol accumulation in both native and transgenic hosts, significantly improving their UV-B resistance. We further discovered that the transcription factor RrNAC2 directly binds to a non-canonical AC-rich repeat within the RrOSC5 promoter, activating its transcription. Crucially, heterologous overexpression of RrNAC2 in tobacco conferred the enhanced UV-B tolerance, establishing its role as a core regulator in this pathway. Notably, we found that the master UV-B signalling regulator RrHY5 physically interacts with RrNAC2, thereby integrating the RrNAC2-RrOSC5 sterol module Into the canonical UV-B signalling pathway. Our findings revealed a hierarchical RrHY5-RrNAC2-RrOSC5 cascade governs UV-B-induced sterol defence, wherein RrNAC2 drives protective sterol biosynthesis via RrOSC5, and both components synergistically enhance antioxidant and osmotic adjustment defences. This work provides novel insights into sterol-mediated plant adaptation to UV-B stress for molecular breeding of fruit plants.
The design and synthesis of novel supports for stabilizing highly active ultrafine metal nanoparticles (MNPs) is critically important across diverse scientific fields as it enables more efficient utilization of their high density of accessible active sites. However, the potential of emerging porous liquid (PL) materials to protect such MNPs remains largely unexplored. Herein, we report the rational design and synthesis of a new PL based on a porous organic cage (POC), termed CPOC-PL, constructed via condensation between four concave tetraformylcalix[4]resorcinarene caps and eight long-chain polyethylene glycol-functionalized diamino imidazole linkers. This [4+8] CPOC-PL features a square-prismatic cavity that serves as an excellent host for encapsulating and stabilizing ultrasmall Pd nanoparticles (∼1.36 nm in diameter) through a coordination-reduction process. The resulting Pd@CPOC-PL exhibits notable hydrogen gas uptake under ambient conditions, with ∼2.1 H atoms per Pd atom. Leveraging its fluidic nature and efficient hydrogen capture ability, Pd@CPOC-PL also demonstrates outstanding catalytic performance in the semihydrogenation of alkynes at ambient conditions. This work presents a generalizable strategy for the rational construction of functional POC-based porous liquids for practical applications.
Intravenous drug incompatibility is a significant medication safety hazard, particularly in complex multidrug regimens. Traditional text-based, pairwise query methods are inefficient and impose a substantial cognitive load on clinicians. While network visualization has the potential to address these challenges, its application in drug compatibility queries remains underexplored. This study aimed to design, develop, and evaluate a novel drug compatibility query system based on a WeChat Mini Program. The system integrates diverse data sources and uses network visualization to present complex compatibility relationships. We sought to empirically assess its impact on efficiency and user experience. A preliminary crossover usability and efficiency evaluation was conducted. Phase 1 involved the construction of a drug compatibility knowledge base from authoritative handbooks and drug labels, and the development of the query system. Phase 2 comprised a system evaluation with 36 pharmacists, 6 physicians, and 5 nurses. The evaluation included a scenario-based task completion time analysis comparing the system (Mode A) with traditional print-based resources (Mode B), a quality assessment using the Mobile Application Rating Scale (MARS), and structured posttask user feedback to gather insights on user experience. The query system demonstrated a substantial reduction in task completion time, with median time savings of 2.85 (IQR 1.98-4.15) minutes, 5.45 (IQR 3.95-7.20) minutes, and 31.2 (IQR 27.5-35.1) minutes, respectively, in 3 scenarios with different complexity. The system received a high mean overall quality score of 3.88 (SD 0.35) on the MARS. The functionality dimension scored the highest (mean 4.21, SD 0.51), while engagement scored the lowest (mean 3.21, SD 0.62). Posttask structured feedback revealed five major areas of user feedback: (1) baseline experience and first impressions, (2) user experience with network visualization, (3) perceived efficiency and cognitive load, (4) trust and information quality, and (5) future application considerations. Users praised the system's efficiency and intuitive design but expressed a strong need for transparent data sources and management advice to build trust. A query system based on network visualization demonstrates potential to support the efficiency of multidrug compatibility queries within this preliminary evaluation. It may mitigate cognitive load and offer an at-a-glance understanding of complex drug relationships. However, formal clinical accuracy validation remains a mandatory precondition before bedside clinical deployment is considered.
The molecular subtype characterized by co-occurring MYD88 and CD79B alterations (MCD) represents a biologically distinct subset of diffuse large B-cell lymphoma (DLBCL) with chronic active B-cell receptor signaling and a high risk of central nervous system (CNS) involvement. The clinical impact of Bruton tyrosine kinase inhibitors (BTKi) in this subtype remains unclear. We retrospectively analyzed 155 patients with newly diagnosed DLBCL harboring genetic features consistent with the MCD subtype. At a median follow-up of 34.1 months, the estimated 3-year progression-free survival (PFS) rate was 76.1%. BTKi exposure (n = 56) was associated with significantly improved PFS compared with no BTKi exposure (3-year PFS: 93.8% vs. 66.6%, p < 0.001) and remained independently associated with improved PFS after adjustment for IPI risk (HR 0.16, p < 0.001). Overall survival did not differ significantly between groups. Notably, all 15 CNS relapse events occurred in patients who did not receive BTKi, whereas no CNS relapse was observed in the BTKi-treated group. BTKi exposure was independently associated with a markedly reduced risk of CNS relapse (HR 0.06, p = 0.002) after adjustment for CNS-IPI risk and CNS prophylaxis. These findings suggest that BTK inhibition may improve outcomes and mitigate CNS relapse in MCD DLBCL.
Psychedelics that target serotonin 2A receptors (5-HT2ARs) hold therapeutic promise for neuropsychiatric disorders but are often hindered by off-target actions. The 5-HT2AR agonist quipazine also activates 5-HT3R, which contributes to undesirable side effects. Here, we developed VCU-1012, a quipazine-based, structurally distinct 5-HT2AR agonist devoid of 5-HT3R activity. VCU-1012 was developed by applying a strategic chemical design that combined deconstruction to pinpoint the nitrogen atom critical for 5-HT2AR activation with structure-activity relationship studies to minimize 5-HT3R agonism. We showed that VCU-1012 modulated dendritic spine structural plasticity in the frontal cortex and produced antidepressant-like effects in mice through 5-HT2AR without activating 5-HT3R, thereby avoiding the gastrointestinal side effects of quipazine. In addition, our molecular modeling and mutant analysis suggested that VCU-1012 interacted in the canonical orthosteric binding pocket of 5-HT2AR. Together, these findings establish VCU-1012 as a potential therapeutic agent with reduced gastrointestinal impact, emphasize how differences in ligand-receptor interactions influence ligand positioning in the receptor binding pocket, and provide guidance for designing psychedelics with targeted therapeutic benefits.
Students with hearing impairments face elevated risks of executive function (EF) deficits due to limited auditory-linguistic scaffolding. Augmented reality (AR) offers visually grounded cognitive rehabilitation affordances aligned with these learners' visual-spatial strengths. This study designed and evaluated an AR-based assistive technology to enhance EF in hearing-impaired elementary students and explored usability from learners' perspectives. An explanatory sequential mixed methods design was employed. In Phase 1 (QUAN), 50 hearing-impaired students (Grades 1-6) were randomly assigned to experimental (n = 25) or control (n = 25) groups across eight AR intervention sessions. In Phase 2 (QUAL), 12 participants were purposively selected via maximum variation sampling for group semi-structured interviews facilitated by Thai Sign Language teachers. Quantitative and qualitative strands were integrated via a joint display. Between-group analysis revealed a significant improvement in verbal working memory (p = .005, r = 0.43; surviving Bonferroni correction, α = 0.008); inhibition response time showed a marginal effect (p = .029) that did not reach the corrected threshold. Codebook thematic analysis (κ = 0.80) produced five themes. Joint display integration yielded four meta-inference types: confirmation (QUAN and QUAL mutually reinforce findings), expansion (QUAL extends interpretation of marginal QUAN effects), discordance-explanation (null cognitive-flexibility effect attributed to limited task variety), and confirmation of null (QUAL corroborates practice/maturation as alternative explanation for within-group TMT gains). AR-based assistive technology grounded in visual-spatial learning principles shows promise for cognitive rehabilitation in hearing-impaired students. Mixed methods integration revealed intervention mechanisms that neither strand could yield independently. AR-based assistive technology that leverages visual-spatial modalities can serve as a viable cognitive rehabilitation tool for children with hearing impairments, particularly for targeting executive functions such as inhibition and working memory that are often underserved by conventional auditory-linguistic approaches.Designing assistive technology in alignment with the ICF framework—addressing activity limitations and participation restrictions rather than impairment alone—can support more holistic rehabilitation outcomes by reducing environmental barriers to cognitive engagement for hearing-impaired learners.Incorporating usability evaluation guided by ISO 9241-11 (effectiveness, efficiency, and satisfaction) into assistive technology development ensures that rehabilitation tools are not only clinically effective but also accessible and acceptable to the target population, which is essential for sustained engagement and real-world adoption.Rehabilitation practitioners working with hearing-impaired children should consider integrating AR-based interventions with visual scaffolding, sign-language support, and immediate feedback mechanisms as complementary tools within cognitive rehabilitation programs, as these features were associated with improved self-regulation, motivation, and confidence among learners.Systematic instructional design models such as ASSURE can provide a structured, replicable framework for developing assistive technologies tailored to specific rehabilitation needs, enabling interdisciplinary teams—including rehabilitation professionals, educators, and technology developers—to collaboratively design evidence-based cognitive rehabilitation tools for diverse populations with sensory impairments.
Osteoporosis can cause painful, disabling, fatal fractures and impose substantial socioeconomic burdens. Because menopause-related bone loss accelerates during midlife, women with limited income may have difficulty accessing screening, counseling, and bone-healthy nutrition before the first fragility fracture occurs. Assessing bone-health awareness and preventive practices in this group may help identify modifiable gaps and guide targeted prevention for low-income midlife and older women. (1) What were the attitudes, awareness, and preventive practices regarding bone health among women age 40 to 65 years with limited income in Shanghai, China? (2) Which sociodemographic and health-related factors were associated with bone-health knowledge scores? We conducted a multidistrict, cross-sectional survey from January to September 2023. We approached 6429 eligible women with limited income at 10 health facilities and community outreach sites in seven Shanghai districts; 94% (6068) completed valid questionnaires and were included in the analysis. Eligible participants were 40 to 65 years of age, had lived in Shanghai for at least 5 years, and received minimum living security assistance. We believe that this group likely is representative of women in this demographic in Shanghai, and may be relevant to similar urban and periurban populations in China and parts of Asia. Data were collected using a researcher-developed questionnaire on osteoporosis knowledge, attitudes, and practices. Multivariable linear regression was used to identify factors associated with knowledge scores. A clear attitude-practice gap was observed. Although 61% (3698 of 6068) of participants considered bone health important, preventive practice was uncommon in the overall cohort: 12% (720) reported calcium supplementation, 9% (520) reported vitamin D supplementation, and 2% (106) reported menopausal hormone therapy use. Twenty percent (1228) selected dual-energy x-ray absorptiometry (DEXA) as their preferred screening method, while 4% (226) had previously undergone DEXA. Higher educational attainment (β = 1.18; p < 0.001), being married (β = 1.14; p < 0.001), and regular physical activity (β = 1.28; p < 0.001) were associated with slightly higher knowledge scores. Hypertension (β = -0.73; p < 0.001) and diabetes (β = -1.10; p < 0.001) were associated with slightly lower scores. Although most participants believed that bone health was important, women age 40 to 65 years with limited income in Shanghai had limited bone-health knowledge and generally did not take preventative steps that could have improved their bone health. These findings support practical, bone-health education in women's screening programs, community clinics, and chronic disease visits. These materials should be tailored to the anticipated reading levels of the populations served. Programs should explain calcium and vitamin D sources, weightbearing exercise, DEXA referral, and postfracture follow-up. Our findings may also be relevant to other urban and periurban populations in China and in other parts of Asia with similar social and economic characteristics.
Develop an evidence-based practice (EBP) mentorship program framework. Despite the widespread call for EBP adoption, EBP competency in healthcare remains low. An integrative literature review across 3 databases on EBP mentorship programs was conducted in August 2025. A total of 21 English-language articles were included in the review. Five core pillars for successful EBP mentorship programs were identified: corporate considerations, mentor development, program design, education, and outcome measurement. Nursing administrators are uniquely positioned to bridge the gap between academia and EBP implementation through mentorship programs that drive EBP competencies, develop champions, and build a sustained culture of inquiry.
As alternatives to bioenzymes, nanozymes find promising applications in biochemical sensing thanks to their recognized superiorities, but their lack of specific interactions with targets of interest seriously hinders the exploration of selective analytical strategies when no external receptors are employed. Additionally, most nanozymes exhibit poor catalytic efficiency, much lower than their natural counterparts, thus restricting the sensitivity of detection. Different from the explored "turn-off" analytical principle relying on the coordination of the target with a nanozyme catalytic product, here we proposed an analyte-unique "signal-on" strategy based on the direct target-nanozyme interaction for the sensitive sensing of uranyl via temperature-programming the peroxidase (POD)-mimetic activity of CoOx. As wet-chemical temperature increased, the oxygen vacancy (OV) content on CoOx surfaces exhibited a volcano-type trend, and its catalytic efficiency correlated with the former positively. UO22+ was found to stimulate the POD-like activity of CoOx via increasing OV, exhibiting excellent specificity against other common species. Leveraging the unique CoOx-UO22+ interaction and the temperature-programmed activity of CoOx, we validated a "light-up" colorimetric approach for UO22+ selective determination, achieving a wide detection range (0.01-2 μM) and a low limit (5 nM). A deployable device based on intelligent reading was further fabricated to enable on-site monitoring of the analyte. Our work provides a "signal-on" nanozyme sensing strategy for the quantification of UO22+, featuring specific response, catalytic signal amplification, and free from bioreceptors. Also, it proves a facile route to achieve dual modulation of enzyme-mimetic activity and analyte response for broader applications.
Mitochondrial biogenesis is a fundamental process that ensures energy supply and supports steroidogenesis in ovarian cells. Lactate has recently been identified as a signaling metabolite that promotes mitochondrial biogenesis; however, the underlying regulatory mechanisms remain poorly defined. Here, we identify Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90α) lactylation as a key mediator that links glycolytic metabolism to mitochondrial function. Specifically, lactylation of HSP90α at K58 recruits ULK1, thereby enhancing phosphorylation at S39; lactylation at K616 prevents CDK5-mediated phosphorylation at S596. This dual regulation facilitates the nuclear translocation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and its isoform LRPGC1, which activate NRF1/2-dependent transcription of mitochondrial biogenesis genes, such as Tfb1m, Tfb2m, and Tfam. Functionally, mitochondrial mass expansion both enhances cellular energy metabolism and promotes cholesterol import into mitochondria, thereby driving estrogen biosynthesis. Together, these findings reveal a lactate-HSP90α-PGC1α/LRPGC1 axis that metabolically couples glycolysis to mitochondrial biogenesis and reproductive hormone production, providing insights into the epigenetic regulation of follicular development.
Digital health literacy is an essential skill for processing health-related information in today's technology-driven society. Recent literature highlights deficits in digital health literacy among adolescents and legislative initiatives to secure its promotion have been introduced (eg, in the German Social Code Book V). However, few interventions target adolescents; existing programs often overlook critical aspects like graph literacy or lack applicability in schools and rigorous scientific evaluation. To overcome these limitations, short mobile interventions-optimized for mobile devices and flexible deployment in schools-were developed to promote digital health literacy. This study aimed to evaluate the effectiveness of one of these interventions (focusing on graph-based health information) and to assess its quality and applicability within educational settings as a proof-of-concept for the further development of similar interventions for adolescents. A randomized-controlled pre-post trial with an active control group was conducted across two independent samples in a web-based survey: adolescents in secondary schools (14-17 years) and teachers. Participants in each sample were randomly assigned (1:1 allocation) to the experimental or control group. Following baseline data collection (T1), participants completed their assigned interventions, immediately followed by postassessments (T2). The experimental intervention is a mobile-friendly e-learning module (approximately 10 minutes) featuring interactive tasks focused on interpreting graph-based health information. The control intervention followed the same design and logic but covered a different topic. The primary outcome was subjective knowledge regarding the intervention's topics. Secondary outcomes included objective knowledge (quiz scores) and 2 adapted subscales of the Digital Health Literacy Instrument (DHLI: "evaluating reliability" and "determining relevance"). Educational quality, visual aesthetics, and practical applicability were also assessed at T2. Among adolescents (experimental group: n=251; control group: n=249), a significant interaction effect was observed only for objective knowledge (F1,498=70.42, η²p=.124; P<.001), but not for the other three outcomes (subjective knowledge: F1,498=2.04, η²p=.004; P=.15; evaluating reliability: F1,498=0.28, η²p<.001; P=.60; determining relevance: F1,498=0.25, η²p<.001; P=.62), meaning that the intervention improved fact-based but not subjective knowledge and no broader health literacy related skills. For teachers (experimental group: n=301; control group: n=302), the results showed significant interaction effects for subjective knowledge (F1,601=32.42, η²p=.051; P<.001), objective knowledge (F1,601=128.79, η²p=.177; P<.001), and one facet of digital health literacy (evaluating reliability: F1,601=6.21, η²p=.010; P=.01), while the interaction effect for "determining relevance" was not significant (F1,601=1.97, η²p=.003; P=.16), suggesting that the intervention improved teachers' knowledge and one facet of digital health literacy. Both samples evaluated the visual and educational quality of the intervention as positive. This study demonstrates that short mobile interventions hold significant promise for the promotion of digital health literacy (eg, graph literacy) within school environments. These interventions can effectively teach objective knowledge to adolescents and teachers, but improving their digital health literacy may require more comprehensive or multimodule approaches. German Clinical Trials Register DRKS00037830; https://drks.de/search/de/trial/DRKS00037830/details.
The clinical translation of nanozymes is hindered by the passive and uncontrollable catalytic properties, necessitating active and precise spatiotemporal regulation. Inspired by the electrostatic preorganization theory of efficient natural enzymes, this review provides a systematic analysis of electric field-regulated nanozymes. Compared to conventional physical stimuli, this approach offers a tunable and complementary framework for active precise therapy. Diverse electrical input modes provide adaptable driving forces for precisely regulating nanozyme catalysis across various biomedical scenarios. Furthermore, at the atomic scale, the underlying mechanisms are elucidated, demonstrating how the electric field inputs optimize the d-band center, surface charges, band structure, and active sites to promote substrate adsorption and lower reaction energy barriers, thereby enhancing the catalytic effect. To maximize electric field-nanozyme coupling, design principles for a complete charge pathway are distilled: optimizing intrinsic field response, directional charge rectification, and achieving low-loss transport. Subsequently, the applications of electric field-regulated nanozymes in precision therapy are summarized, including on-demand spatiotemporal activation, quantitative dosage regulation, and active microenvironment remodeling. Finally, this review highlights the immense potential of interdisciplinary integration in overcoming the biosafety and mechanism bottlenecks of this regulation strategy. These insights provide a new perspective for advancing electric field-regulated nanozymes toward precision therapy.
Cardiac abnormalities are among the most common and complex risk factors of pediatric acute ischemic stroke (AIS). Although endovascular treatment (EVT) is increasingly used in children, uncertainty persists regarding its safety and effectiveness in patients with underlying cardiac disease, leading to therapeutic hesitation in this high-risk population. The aim of this study was to determine whether the association between EVT and functional outcomes after pediatric AIS differs according to cardiac abnormality status. This study was a retrospective secondary analysis of a prospective, multinational cohort registry (Save ChildS Pro). The registry enrolled patients between 2018 and 2023, with 90-day follow-up. Participants included children aged 28 days to 18 years with confirmed AIS due to large vessel occlusion and available 90-day Pediatric Stroke Outcome Measure (PSOM) scores. Cardiac abnormalities were defined as congenital or acquired cardiac disease documented by echocardiography or medical records. The primary outcome was poor functional outcome at 90 days, defined as PSOM score >0.5. Secondary outcomes included ordinal 90-day modified Rankin Scale (mRS) scores and longitudinal neurologic recovery assessed using the Pediatric NIH Stroke Scale (pedNIHSS). Treatment-subgroup interaction was assessed using penalized logistic regression. Of 208 eligible patients, 178 were included in the final analysis after excluding those with missing outcome data [43% female; mean age: 11.5 years]. Among 178 children, 56 (31.5%) had cardiac abnormalities. EVT was more frequently performed in children with cardiac abnormalities than in those without (p = 0.003). Cardiac abnormality status was not independently associated with outcome (odds ratio, 0.93; 95% CI, 0.36-2.52), and no significant interaction between EVT and cardiac abnormality was observed. Ordinal mRS shift analysis and longitudinal pedNIHSS modeling supported similar recovery trajectories. Adverse event rates did not differ by EVT status in either subgroup. In this multinational pediatric AIS cohort, EVT was associated with improved functional outcomes and accelerated neurologic recovery, with no evidence that cardiac abnormality status modifies association of treatment with outcome or safety. These findings support consideration of EVT in children with cardiac abnormalities when clinically indicated. This study provides class IV evidence that endovascular therapy in pediatric patients with AIS is associated with improved functional outcome irrespective of underlying cardiac abnormality status.
Perfluorobutanesulfonic acid (PFBS), a short-chain per- and polyfluoroalkyl substance (PFAS) adopted as a replacement for perfluorooctane sulfonate (PFOS), is ubiquitously detected in environmental matrices and human biological samples. Despite growing regulatory concern, the molecular mechanisms by which PFBS affects prostate tissue at environmentally relevant concentrations remain poorly characterized. In the present study, we exposed human prostate epithelial (RWPE-1) and stromal (WPMY-1) cells to PFBS (0-100 nM, 24 h) and integrated in vitro mechanistic analyses with genome-wide RNA sequencing (RNA-seq), Gene Ontology (GO) enrichment, KEGG pathway analysis, and protein-protein interaction (PPI) network clustering. At concentrations maintaining cell viability above 80%, PFBS induced opposing responses in the two cell types. In RWPE-1 epithelial cells, PFBS activated the PI3K-AKT-GSK3β axis with concurrent nuclear β-catenin accumulation, upregulation of Wnt target genes, S-phase entry, and induction of an IGF-1/IGF-2 autocrine loop. In WPMY-1 stromal cells, PFBS suppressed the PI3K-AKT axis, induced G0/G1 arrest, caused approximately 400% ROS elevation, depolarized mitochondrial membranes, decreased GPX4, and upregulated ACSL4 and intracellular Fe2 + accumulation, collectively suggesting heightened ferroptosis susceptibility, along with reduced expression of stromal paracrine factors (FGF7, FGF10 and HGF). RNA-seq and bioinformatics analyses revealed markedly divergent transcriptional landscapes between two cell types. GO enrichment identified phospholipid metabolic process and Wnt signaling as the dominant RWPE-1 programs, and extrinsic apoptotic signaling and mitochondrion organization regulation in WPMY-1. These findings suggest that, under these in vitro conditions, PFBS can simultaneously activate Wnt signaling in epithelial cells and promote ferroptosis susceptibility in stromal cells, a divergent response pattern not captured by conventional single-endpoint toxicity assays. As these observations were obtained in isolated monocultures, they should be interpreted as cell-autonomous vulnerabilities that require validation in co-culture, organoid, and in vivo systems before any inference regarding human systemic risk can be drawn.
Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) drive multiple aggressive lymphomas, yet effective targeted therapies for these virus-associated malignancies remain limited. Using an unbiased kinome-wide screen combined with analysis of virus-positive patient tumors, we identified fibroblast growth factor receptor 2 (FGFR2) as a selectively activated host kinase in EBV- and KSHV-associated lymphomas. Importantly, FGFR2 is required for efficient establishment of EBV latent infection, and its knockdown markedly impairs the formation of viral latency programs. Viral latency proteins EBV nuclear antigen 2 (EBNA2) and latency-associated nuclear antigen (LANA) recruit STAT3 and RBP-Jκ to the FGFR2 promoter to drive its transcription, enabling efficient establishment of EBV latency and activation of downstream STAT3/AKT signaling. This feed-forward signaling circuit suppresses apoptosis, promotes S-phase progression, and sustains proliferation of infected lymphoma cells. Targeting FGFR2 genetically or pharmacologically using clinically relevant inhibitors markedly suppresses tumor growth in vitro and in vivo. This study identifies FGFR2 as a critical oncogenic driver in EBV and KSHV infections, highlighting its potential as a therapeutic target to inhibit tumor growth and treat associated viral malignancies.