Salvianolic acid B (SalB) is a bioactive polyphenol with therapeutic potential for vascular dementia (VD), but poor penetration across the blood-brain barrier (BBB) and low bioavailability restrict its clinical translation. To address these problems, a SalB-loaded liquid crystalline nanoparticle delivery system (SalB-LCN) was constructed and systematically characterized in terms of its physicochemical properties. Meanwhile, an intranasal administration strategy was employed to bypass the BBB, and the therapeutic effects of SalB-LCN on VD were systematically evaluated. The results showed that SalB-LCN possessed favorable morphology and sustained-release properties, enabling stable encapsulation and continuous release of SalB. In vitro experiments demonstrated that SalB-LCN exhibited good biocompatibility and could alleviate oxidative damage in neuronal cells. In a bilateral common carotid artery occlusion-induced rat model of VD, SalB-LCN significantly improved learning and memory abilities, alleviated hippocampal neuronal morphological damage, and exhibited good in vivo biosafety. Further studies showed that SalB-LCN markedly lowered reactive oxygen species levels, suppressed IL-1β and IL-18 production in hippocampal tissues, and reduced cell death as well as lactate dehydrogenase activity. In addition, SalB-LCN also suppressed NLRP3/Caspase-1/GSDMD signaling. In conclusion, intranasal delivery of SalB-LCN improved brain delivery by facilitating transport across the BBB and conferred neuroprotection against VD through modulation of oxidative stress, inflammation, and NLRP3/Caspase-1/GSDMD signaling, highlighting its translational potential as a nanomedicine-based therapeutic strategy.

Active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) requires intensive immunosuppressive therapy, but continued treatment beyond remission risks serious harm. Because reliable biomarkers of remission are lacking, clinicians often prolong cost-intensive and toxic therapy unnecessarily. Here, we explore the plasma proteome to identify reliable biomarkers of disease remission in patients with AAV, adjusting for patient characteristics and clinical variables. Applying a two-tiered proteomics strategy that combines global discovery with targeted validation, we identify a protein signature of remission. We then implement the resulting 7-protein panel in a targeted mass spectrometry-based assay and confirm its diagnostic performance in an independent patient cohort. The panel consistently outperforms routine markers such as C-reactive protein and ANCA titer. Our findings suggest that this 7-protein panel provides a starting point for developing a clinical tool to support decision-making, with the potential to reduce treatment-related burden, mitigate toxicity, and lower healthcare costs. More broadly, our confounder-controlled proteomics approach provides a scalable blueprint for biomarker discovery in complex inflammatory diseases.

Currently, a large number of drugs with cardiotoxicity are being withdrawn from the market during the clinical use stage, and the types of drugs available for cardiovascular diseases are limited. Two-dimensional models can be utilized to a certain extent to identify drugs with the potential to treat cardiovascular diseases and screen for cardiotoxicity. Still, they fail to reflect the complex physiological activities of the human body accurately. Three-dimensional (3D) models of cardiac tissue have the advantage of simulating the cardiac tissue of the human body, thereby enhancing the efficiency and accuracy of drug sensitivity and toxicity screening. This paper examines the types, advantages, disadvantages, and current situation of drug assessment in 3D cardiac tissue models and discusses the common cardiovascular disease models and the application progress in drug research, providing an outlook for the future development trend of 3D cardiac tissue engineering.

Hypoxic-ischaemic encephalopathy (HIE) is a leading cause of neonatal mortality and long-term neurodevelopmental impairment worldwide. Neonatal seizures are common in HIE and are associated with adverse outcomes. While antiseizure medications are routinely used for treatment, their prophylactic use in the absence of clinically evident seizures remains controversial, with limited consensus and variable clinical practices. Therefore, this review will map the existing evidence concerning the utilisation of antiseizure medication for prophylaxis among neonates with HIE.

The review will follow the Joanna Briggs Institute scoping review methodology and be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive search will be conducted across various scientific databases, including PubMed, Embase, Scopus and Web of Science, guided by the Population, Intervention, Concept and Context framework, starting between October and November 2026. The review will consider studies on the prophylactic use of antiseizure medication among neonates with HIE. The collected search results will be organised and uploaded to Covidence, where duplicates will be removed, and titles and abstracts will be screened. Search and screening processes have not yet started.

This will be a secondary study using already published information; therefore, ethical approval was not sought. All studies included in this review will be cited accordingly, as attributed to the publication licence. The data gathered will be summarised in a scoping review and submitted for publication in an international peer-reviewed journal. Datasets shall also be made publicly available in a data repository, such as the Open Science Framework.

Chronic kidney disease is a central node of the cardio-kidney-metabolic continuum and carries substantial residual cardiovascular and kidney risk. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have reproducibly reduced kidney disease progression and heart failure risk in CKD outcomes trials, whereas GLP-1RAs have established cardiovascular benefit across cardiometabolic populations. The FLOW trial (Evaluate Renal Function With Semaglutide Once Weekly) established hard kidney-outcome evidence for semaglutide in type 2 diabetes with CKD, although whether this renal benefit represents a broader GLP-1RA class effect remains unresolved. This review synthesizes current evidence through a translational framework centered on mechanistic complementarity rather than simple add-on therapy. SGLT2 inhibitors predominantly provide proximal tubular and hemodynamic offloading, coupled with fasting-mimetic metabolic reprogramming that may improve oxygen-stress balance and cellular housekeeping. GLP-1RAs predominantly support an immune-vascular repair program by dampening sterile inflammation, preserving endothelial integrity, and limiting fibrotic amplification. These pathways appear to converge at mitochondrial homeostasis, autophagy, and barrier stability. We argue that the most useful clinical implication at present is not a fixed prescribing algorithm, but a phenotype-aware way to frame residual risk, sequence future studies, and define mechanistic endpoints for combination strategies across chronic kidney disease phenotypes.

The frequency of heart failure and hyperuricemia is increasing worldwide. Hyperuricemia as a complication of heart failure is known to be an indicator of poor prognosis. However, no consensus exists on whether treating hyperuricemia as a complication of heart failure would alleviate symptoms or improve prognosis in patients with heart failure. There is insufficient evidence regarding whether treatment with uric acid-lowering agents can alleviate symptoms and improve prognosis in patients with heart failure. However, considering the prevention of gout, hypertension, and chronic kidney disease caused by hyperuricemia, if the serum uric acid level does not fall below 8 mg/dL with improvement in lifestyle habits, uric acid-lowering agents can be a treatment option. In an US cohort study comprising approximately 100,000 participants using Medicare data, less aggravation of heart failure was observed in patients who were administered febuxostat compared to allopurinol. Recent evidence further suggests that serum uric acid may reflect not only a biomarker of disease severity but also underlying xanthine oxidase activity and oxidative stress, which may be therapeutically targetable in selected subgroups of heart failure patients. Moreover, differential effects among uric acid-lowering agents raise the possibility that drug-specific properties, rather than uric acid reduction per se, may influence cardiovascular outcomes. In this review, we discuss clinical trials on hyperuricemia with heart failure and its treatment. Further large-scale, high-quality, prospective intervention studies on the efficacy of treating hyperuricemia as a complication of heart failure are required.

Inhibitor-κB kinase epsilon (IKKε) is a non-canonical IκB kinase involved in NF-κB signaling and type I interferon responses. We recently demonstrated sex-dependent effects of IKKε deletion on atherosclerosis and metabolic dysfunction-associated steatotic liver disease (MASLD), with male knockout mice showing protection against both diseases, while female mice exhibited exacerbated inflammatory and metabolic disturbances. These divergent outcomes were linked to differential effects on inflammatory pathways and lipid metabolism.

To evaluate the therapeutic potential of pharmacological IKKε inhibition, we treated wild type mice with established atherosclerotic plaques and hepatic steatosis - induced by PCSK9 gain-of-function and Paigen diet - with the IKKε inhibitor amlexanox.

Amlexanox modulated serum lipid levels and altered plaque composition but did not halt plaque progression. In the liver, treatment produced marked sex-specific effects: male mice exhibited substantial improvement in steatosis, whereas female mice showed worsened lipid accumulation. These outcomes were reflected in pronounced sex-dependent differences in serum and hepatic lipid and metabolite profiles, indicating regulation of fatty acid and bile-acid metabolism predominantly in males. Protein analyses in liver and adipose tissue further supported opposing metabolic and inflammatory responses between sexes after amlexanox treatment.

Collectively, our findings indicate that therapeutic IKKε inhibition with amlexanox does not prevent progression of advanced atherosclerosis in this model but effectively ameliorates MASLD in male mice. In contrast, female mice experience aggravated hepatic lipid deposition. These results underscore the importance of incorporating sex-specific analyses in metabolic and cardiovascular research and highlight the need to evaluate therapeutic strategies such as amlexanox in both sexes.

The rising global burden of diseases linked to reactive oxygen and nitrogen species (ROS/RNS) - including inflammatory disorders, cancers, neurodegenerative conditions, and cardiovascular disease - has intensified interest in enzyme-mimicking nanomaterials (nanozymes) as tools to modulate cellular redox balance. Natural antioxidant enzymes, chiefly superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), are the principal enzymatic defenses against oxidative stress, but their clinical use is limited by poor stability, short half-life, and high cost. Nanozymes, producible at scale with tunable, stable activity, offer a promising alternative. This review is organized around a mechanistic distinction essential to the literature but frequently blurred: antioxidant nanozymes, which net-scavenge ROS through reversible redox cycling, versus pro-oxidant nanozymes, which net-generate ROS through Fenton-type chemistry. Cerium oxide nanoparticles (CeO₂ NPs) are examined as the prototypical antioxidant nanozyme, their SOD- and CAT-like activities arising from reversible Ce³⁺/Ce⁴⁺ cycling and oxygen-vacancy chemistry at the surface, with the Ce³⁺/Ce⁴⁺ ratio determining which activity predominates. Magnetite nanoparticles (Fe₃O₄ NPs) are examined as the prototypical pro-oxidant nanozyme, dominated by peroxidase-like Fenton chemistry driven by surface Fe²⁺/Fe³⁺ cycling that generates hydroxyl radicals, exploited for antibacterial and antitumour applications, with CAT-/SOD-like activity arising only as a secondary, concentration- and pH-dependent behaviour. Beyond mechanism, this review surveys the expanding application space for both classes, including ROS/analyte sensing, antibacterial therapy against resistant pathogens, diabetic wound healing, treatment of ROS-associated disease, and catalysis by related metal-oxide nanocatalysts. By keeping the two tracks mechanistically distinct, this review provides a clearer framework for rational nanozyme-based therapeutic design.

Changes in the gut microbiota occur throughout the human lifespan, and maintaining microbial homeostasis plays a critical role in promoting healthy aging. In recent years, substantial progress has been made in elucidating the mechanistic links between aging and microbiota remodeling, highlighting the central role of microbiota-host interactions in regulating immune responses and maintaining metabolic homeostasis. These findings provide new potential targets for the precision prevention and treatment of age-related diseases. This review systematically summarizes the patterns of gut microbiota succession across different stages of the human life cycle, including infancy, adolescence, adulthood, and old age, as well as the mechanisms through which the microbiota regulates immune and metabolic functions. Furthermore, the role of the gut microbiota as a key mediator linking aging with an increased risk of chronic inflammation, cardiovascular disease, cognitive impairment, neurodegenerative disorders, and cancer was explored. In addition, this review evaluates the therapeutic potential of microbiota-targeted interventions, such as dietary modification, probiotic and prebiotic supplementation, fecal microbiota transplantation (FMT), and lifestyle interventions-in maintaining microbiome homeostasis and mitigating age-related diseases. The feasibility of personalized microbiota-based intervention strategies is also discussed. Finally, we highlight the current challenges and limitations in this field and outline future research directions. In particular, integrating multi-omics approaches with metagenomic sequencing, including emerging spatial and spatiotemporal multi-omics technologies, is crucial for advancing our understanding of the complex interactions within the gut microbiome. These insights provide a theoretical framework for optimizing anti-aging therapeutic strategies and promoting healthy lifespan extension.

Prospective evidence linking greenness and cardiovascular disease (CVD) in rapidly urbanizing developing countries remains limited. Here, among 159,590 adults aged ≥40 years from the nationwide China Cardiometabolic Disease and Cancer Cohort with a median follow-up of 10.1 years, we examine the association between residential greenness, measured by satellite-derived normalized difference vegetation index (NDVI) within 500 m of residence, and incident CVD, and evaluate its joint effects with cardiovascular health as defined by Life's Essential 8. Individuals in the highest quartiles of contemporaneous, one-year, and cumulative NDVI consistently show lower CVD risk compared with those in the lowest quartiles, although associations vary across subpopulations. Notably, individuals with high cardiovascular health scores living in low-NDVI areas exhibit similar CVD risk to those residing in high-NDVI areas. These findings highlight the complementary importance of both green infrastructure and healthy lifestyles in reducing CVD risk in rapidly urbanizing regions of China.