To evaluate associations of cardiovascular health (CVH) based on Life's Essential 10 (LE10) with all-cause mortality, cardiovascular disease (CVD) and cancer mortality and incidence, and life expectancy free of CVD and cancer.

This prospective study included 110,806 UK Biobank participants (aged 37-73) and 20,031 National Health and Nutrition Examination Survey (NHANES) participants (aged ≥20). LE10 (0-100), which integrates alcohol consumption and mental health with Life's Essential 8, categorised CVH as low (<60), moderate (60-79), and high (≥80). Cox regression and competing risk models were applied to estimate adjusted hazard ratios (aHRs). Life expectancy was calculated using multi-state and flexible parametric survival models. Over a median follow-up of 13.8 years, 6137 deaths, 13,968 CVD events, and 18,077 cancer cases were documented in UK Biobank. In UK Biobank, high CVH was associated with lower risks of all-cause mortality (men: aHR 0.43, 95% CI 0.39-0.48; women: aHR 0.34, 95% CI 0.29-0.39), alongside CVD and cancer mortality and incidence, compared to low CVH. At age 50, high CVH conferred greater projected overall (men +5.47 years, women +5.85) and disease-free life expectancy (men +4.02 years, women +4.40). Having more low-risk CVH metrics was associated with up to 9.73 years of projected gains in life expectancy. Associations were replicated and consistent in 7.2-year NHANES follow-up.

Higher LE10-based CVH levels were associated with lower all-cause mortality, reduced CVD and cancer mortality and incidence, and longer life expectancy free of CVD and cancer. LE10 may provide additional targets for CVH management.

BACKGROUND Evaluation of multidrug-resistant hypertension in young adults requires consideration of uncommon secondary etiologies, including renovascular disease and congenital renal vascular anomalies. Renal arteriovenous malformations (rAVMs) represent a rare cause of secondary hypertension, accounting for less than 0.1% of renal vascular abnormalities. They most commonly present with hematuria, flank pain, or, in high-flow lesions, high output cardiac failure. Hypertension as the principal manifestation is uncommon. CASE REPORT We describe a 33-year-old woman with longstanding uncontrolled hypertension requiring 5 antihypertensive agents who presented for evaluation of refractory blood pressure control. Initial duplex ultrasound and angiography identified a large complex left renal lesion associated with dysmorphic parenchyma and aberrant arterial and venous architecture without a history of trauma, intervention, or prior renal surgery, consistent with a congenital vascular malformation. Diagnostic computed tomography angiography demonstrated a 6.5×6.5×5.5 cm arteriovenous malformation. Given the lesion's size and vascular complexity, endovascular embolization was deemed not technically feasible. The patient subsequently underwent elective simple nephrectomy without intraoperative complication. Histopathology confirmed a congenital high-flow rAVM with extensive parenchymal distortion. Postoperatively, the patient exhibited marked improvement in blood pressure control, eliminating the need for antihypertensive medication. CONCLUSIONS This case illustrates an uncommon presentation of severe drug-resistant hypertension in a young patient likely attributed to a large congenital rAVM. Congenital renal vascular malformations should be considered in the differential diagnosis of refractory hypertension. Surgical intervention remains an important therapeutic option when endovascular treatment is contraindicated or considered unlikely to preserve functional renal parenchyma.

This study examined the association of weekly plant-based medically tailored groceries (MTGs) with cardiovascular-kidney-metabolic outcomes among patients with food insecurity. The intervention began on December 20, 2019, and ended on April 1, 2025 (275 weeks). Linear mixed-effects models estimated the dose-dependent association of MTGs received and the rates of changes in blood pressure, glycated hemoglobin A_1c, weight, and body mass index from baseline to follow-up periods. Among 68 adults, during an average of 2.7 years, each 100 MTGs received was associated with a greater improvement from baseline to follow-up periods in the rates of changes in diastolic blood pressure (-3.21 mm Hg; 95% CI, -4.89 to -1.52), weight (-2.63 kg; 95% CI, -3.73 to -1.53), and body mass index (-1.04 kg/m²; 95% CI, -1.50 to -0.58).

α-Lipoic acid (LA) is a naturally occurring small molecule possessing both endogenous cofactor activity and dynamic covalent polymerization capability. The 1,2-dithiolane ring in its structure enables both redox-responsive biological functions and ring-opening polymerization to yield polylipoic acid (PolyLA) with a dynamic disulfide backbone, bridging small-molecule medicinal chemistry and functional polymeric materials within a single molecular platform. This Review systematically outlines the full landscape of LA research, covering its chemical foundations, biological functions, polymer chemistry, and biomedical applications. We elaborate on the multi-pathway redox and anti-inflammatory network of LA and its reduced form, as well as their vital roles as mitochondrial cofactors in energy metabolism and insulin sensitivity. We then compare the mechanisms and applicable scenarios of various ring-opening strategies, dissect the origin of room-temperature PolyLA depolymerization, and summarize the corresponding stabilization strategies. Further, we propose a three-stage evolutionary framework for LA-based nanoscale delivery systems, ranging from physical encapsulation and chemical conjugation to the therapeutic self-carrier paradigm; we also systematically recapitulate their design rationales and mechanisms in treating tumors, nerve injury, diabetic complications, inflammatory diseases, and cardiovascular diseases. As for dynamic biomaterials, PolyLA-based adhesives and flexible sensors leverage dynamic disulfide bonds and carboxyl groups to achieve universal adhesion, tissue integration, self-healing, and recyclable properties. Finally, we identify the core bottlenecks hindering clinical translation and outline forward-looking outlooks for this field. By establishing an integrated framework that connects molecular structure to multifunctional applications of LA-based biomaterials, this Review highlights how interdisciplinary integration unlocks innovative research avenues and accelerates the clinical translation of LA-derived therapeutics and biomaterials.

Aconitine-induced cardiotoxicity is a serious adverse effect of Aconitum-containing medicines, with myocardial injury and malignant ventricular arrhythmias representing important clinical manifestations. However, the molecular responses underlying aconitine-induced myocardial injury remain incompletely understood. This study aimed to construct an integrated molecular network and signaling pathway landscape of aconitine-induced cardiotoxicity through multi-cohort transcriptomic analysis and to identify key hub genes associated with myocardial injury and ventricular tachyarrhythmias. Rat myocardial transcriptomic datasets related to aconitine-induced cardiotoxicity were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the thresholds of |log₂FC| > 1 and a false discovery rate (FDR) < 0.05. Weighted gene co-expression network analysis (WGCNA) was performed to identify cardiotoxicity-associated gene modules, and candidate genes were obtained by intersecting DEGs with module genes. Protein-protein interaction (PPI) network analysis was subsequently conducted to identify hub genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to characterize their biological functions and signaling pathways. The expression patterns of the hub genes showed broadly concordant trends in the independent doxorubicin-induced cardiotoxicity dataset, suggesting that these genes may represent conserved transcriptional responses to myocardial injury (GSE42177). A total of 265 DEGs were identified, and WGCNA revealed one gene module significantly associated with cardiotoxicity (r = - 0.33, P < 0.001). Integration of DEGs with the cardiotoxicity-associated module yielded 18 candidate genes, from which 12 hub genes (Abcb11, Abcc6, Fez1, Ldha, Nr3c1, Nr3c2, Pc, Pdk2, Prkcz, Slc9a1, Vcam1, and Vtn) were identified through PPI network analysis. Functional enrichment analysis indicated that these genes were primarily involved in inflammatory responses, metabolic regulation, and stress-related signaling pathways, particularly the MAPK and TGF-β signaling pathways.

Diabetic ulcers (DU) are a severe complication of diabetes mellitus and are associated with infection, recurrence, amputation, and excess mortality. Robust molecular markers that distinguish ulcer tissue from non-ulcer tissue and clarify the biological basis of impaired healing remain limited.

Public transcriptomic datasets were integrated to identify DU-associated genes initially selected from lipid metabolism-related gene sets. Differential expression analysis, random forest modeling, single-sample gene set enrichment analysis (ssGSEA), gene set enrichment analysis (GSEA), Gene Set Variation Analysis (GSVA), drug-gene interaction analysis, and single-cell RNA sequencing were used to prioritize candidate biomarkers. External transcriptomic cohorts were used for validation. A streptozotocin-induced diabetic wound model in C57BL/6 mice was evaluated by serial wound imaging, hematoxylin and eosin staining, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blotting. A ten-gene panel comprising ANGPTL4, BNIP3, EEF2K, EIF4EBP1, KLHDC1, KLK10, KLK8, NFIX, QSOX1 and S100A8 showed strong discrimination and reproducible expression patterns across validation datasets. Immune analyses linked the panel to T helper 17 (Th17) cell infiltration and interleukin receptor activity. Single-cell analysis localized these genes to distinct wound-associated cell populations. Diabetic mice exhibited delayed wound closure and greater residual wound widths than control mice. Transcript and protein assays showed concordant changes in representative genes.

These findings identify a candidate biomarker panel for DU and connect its transcriptomic pattern with immune remodeling, cell-specific expression, and impaired wound repair. Further validation in larger human cohorts is required before clinical application.

Transthyretin amyloid cardiomyopathy (ATTR-CM) causes heart failure and poor outcomes. Prognostic stratification is fundamental, yet validated staging systems rely exclusively on biomarkers, neglecting structural and functional cardiac parameters.

This study evaluates a noninvasive hemodynamic echocardiographic approach to stratify patients with ATTR-CM.

Patients were categorized into 3 groups based on stroke volume index (SVi) and systolic pulmonary artery pressure (sPAP), markers of forward flow and elevated filling pressures. We compared receiver operating characteristic curves for various potentially predictive hemodynamic parameters to identify these as the most robust candidates for risk stratification. Optimal cutoffs (30 mL/m² for SVi and 40 mm Hg for sPAP) were determined using the Liu index, supported by both univariable and multivariable survival analyses. The primary endpoint was the composite of all-cause mortality and heart failure hospitalization. Prognostic utility was evaluated using multivariable Cox regression, adjusted for age, sex, and disease-modifying therapy.

The cohort included 293 patients with ATTR-CM: group 1 (normal SVi/sPAP, n = 115 [39%]), group 2 (low SVi or high sPAP, n = 129), and group 3 (low SVi/high sPAP, n = 49). The primary outcome occurred in 108 (37%) patients. The multivariable analysis confirmed the staging system as an independent predictor of the composite outcome (group 2 HR: 1.70, 95% CI: 1.05-2.71; group 3 HR: 2.50, 95% CI: 1.44-4.30; P < 0.001).

The noninvasive hemodynamic approach provides an alternative and promising method to stratify the risk of clinical outcome in patients with ATTR-CM, potentially improving management strategies.

Mosaic loss of the Y chromosome (mLOY) is a male‑specific somatic loss of the Y chromosome that is predominantly observed in peripheral blood leukocytes, but can also be found in other tissue types. It represents one of the most common male-specific somatic mutations, particularly prevalent in aging individuals. Accumulating evidence shows that mLOY markedly increases the incidence, progression, and adverse prognosis of multiple diseases, including, but not limited to, myocardial fibrosis, lung and bladder cancers, and Alzheimer's disease. Mechanistically, for extrinsic effects of mLOY, hematopoietic mLOY affect other cell populations, thereby promoting disease initiation and progression. From an intrinsic effects, mLOY within cells reprograms autosomal gene expression and reshapes interactions with the immune microenvironment, jointly driving malignant evolution. In this review, we summarize the current understanding of both intrinsic and extrinsic mLOY effects on immune regulation and disease pathogenesis, highlighting its multifaceted roles across cancer, cardiovascular disorders, infections, and other mLOY-associated conditions.

For persons living with both type 2 diabetes and obesity, weight management may be the most effective therapy for type 2 diabetes. Glucagon-like peptide-1 (GLP-1) receptor agonists have potent weight-reducing effects, and other mechanisms may confer additional benefits. Survodutide is an investigational glucagon receptor-GLP-1 receptor dual agonist with potential weight-reducing and metabolic benefits.

In this multinational, double-blind, phase 3 trial involving adults with type 2 diabetes and a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 27 or more, we randomly assigned participants in a 1:1:1 ratio to receive once-weekly subcutaneous survodutide (3.6 mg or 6.0 mg) or placebo. The two primary end points were the percent change in body weight and a reduction in body weight of at least 5% from baseline to week 76.

Among 752 participants (250 in the 3.6-mg survodutide group, 251 in the 6.0-mg survodutide group, and 251 in the placebo group), the mean age at baseline was 55.7 years, and the mean BMI was 36.5; 49.3% were men. The mean weight change at week 76 according to the treatment-regimen estimand (which assessed effects regardless of whether the trial regimen was discontinued or interrupted or whether other antiobesity therapies were used) was -8.2% (95% confidence interval [CI], -9.2 to -7.2) in the 3.6-mg group, -9.8% (95% CI, -10.8 to -8.8) in the 6.0-mg group, and -3.9% (95% CI, -4.9 to -2.9) in the placebo group; weight reduction of at least 5% occurred in 57.6%, 64.5%, and 35.1% of the participants, respectively (P<0.001 for all comparisons with placebo). The mean change in the glycated hemoglobin level (from a baseline level of 7.4%) was -0.9 percentage points in the 3.6-mg group, -0.8 percentage points in the 6.0-mg group, and -0.2 percentage points in the placebo group. The most common adverse events were gastrointestinal (generally mild to moderate and transient), which occurred in 182 participants (72.8%) in the 3.6-mg group, 195 (77.7%) in the 6.0-mg group, and 97 (38.6%) in the placebo group.

In adults with obesity and type 2 diabetes, survodutide at a weekly dose of 3.6 mg or 6.0 mg resulted in significantly greater weight reduction than placebo. (Funded by Boehringer Ingelheim; SYNCHRONIZE-2 ClinicalTrials.gov number, NCT06066528.).

Diabetic foot ulcers (DFUs) affect approximately 18.6 million people worldwide each year. Abnormal plantar pressure during the perioperative period impairs wound healing and promotes ulcer recurrence. Although offloading interventions are fundamental to DFU management, available evidence remains fragmented, and clinical implementation lacks standardization, particularly in perioperative settings. This systematic review and evidence synthesis aimed to systematically retrieve, appraise, and synthesize the best available evidence on perioperative offloading management for DFU patients and to provide evidence-based recommendations for clinical nursing practice. A systematic search following the "6S" evidence pyramid model was conducted across PubMed, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Biomedical Literature Database (CBM) databases, as well as professional society websites, from January 2015 to March 2025. Eligible publication types included clinical guidelines, expert consensus statements, clinical decisions, evidence summaries, and systematic reviews. Quality appraisal used the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument for guidelines and Joanna Briggs Institute (JBI) critical appraisal tools for systematic reviews and expert consensus. Evidence was graded using the JBI Evidence Grading System (2014 version). Fifteen publications were included: 8 guidelines, 2 expert consensus statements, and 5 systematic reviews. Thirty-one evidence items were summarized across seven domains: perioperative risk screening and assessment, multidisciplinary team composition, surgical strategy selection, offloading principles, preoperative offloading, postoperative offloading, and health education with monitoring. Evidence levels ranged from 1 to 5, with the majority at Level 5. This systematic review synthesizes comprehensive evidence on perioperative offloading management in patients with DFU. Healthcare providers should contextualize evidence selection based on clinical settings and individual patient characteristics to optimize wound outcomes and quality of life.