Cigarette smoking and hyperlipidemia are major risk factors for cardiovascular disease. However, the mechanisms underlying their synergistic cardiotoxic effects remain insufficiently elucidated, particularly at the cellular electrophysiological level. To address this, we developed an electrophysiological biosensing platform to establish a real-time co-exposure model that simulates the combined stress of nicotine and palmitic acid-induced hyperlipidemia on the primary rat cardiomyocytes. This model enabled continuous, non-invasive monitoring and quantitative analysis of field potential under individual and combined conditions. Our results revealed a distinct concentration-dependent effect of nicotine on cardiomyocytes: low-dose nicotine induced transient and reversible electrophysiological suppression, while high concentrations triggered severe arrhythmias and cell death. Critically, the co-exposure model revealed that a hyperlipidemic state significantly sensitizes cardiomyocytes to nicotine, markedly exacerbating arrhythmogenesis and compromising cell viability compared to nicotine alone. Moreover, nicotine withdrawal experiments showed that the electrophysiological damage induced by moderate nicotine exposure was reversible, whereas the adverse effects of high-dose nicotine exposure were largely irreversible. This study establishes an in vitro model to investigate the multifactorial cardiotoxicity, and provides a predictive platform for risk stratification and therapeutic intervention in smoking- and/or diet-related cardiovascular diseases.

Controlling blood pressure (BP) reduces cardiovascular morbidity and mortality but is often not achieved in clinical practice. Tailoring therapy to an individual's hemodynamic profile using impedance cardiography (ICG) might attain efficient, effective BP control.

An observational study of hypertensive patients managed by two large U.S. primary care groups (PriMED and Premier) used therapeutic algorithms based on ICG-derived hemodynamics linked to clinical decision support tools to promote physician and patient engagement and medication adherence. The main outcome of interest was BP control according to contemporary (2014) guidelines (<140/<90 mmHg). A subset of PriMED patients was followed for six years, to evaluate clinical outcomes. Clinical information was extracted from electronic medical records.

Of 14,058 patients, median (interquartile range (IQR)) age was 62 (51 to 71) years, 50% were women, and initial systolic and diastolic BP were 152 (145-162) mmHg and 90 (80-98) mmHg. The hemodynamic profile was vasoconstriction for 6,609 (47%) patients, hyperdynamic for 3,365 (24%) and mixed for 4,084 (29%). For PriMED, 92% achieved BP control at the second follow-up visit. For Premier, 81% achieved control at second follow-up, and 91% by the fourth visit, with annual control rates thereafter ranging from 82% to 93%. For 2,955 patients continuously managed by PriMED between 2016-2022, annual rates of myocardial infarction and stroke were 0.30% and 0.43%.

Tailoring anti-hypertensive therapy according to hemodynamic profile in primary care is feasible, providing rapid and sustained BP control with low rates of myocardial infarction and stroke.

The identification of reliable biomarkers of ageing represents a major challenge in biomedical research, particularly in the context of increasing life expectancy and the growing burden of chronic diseases. Among potential candidates, the ABO blood group system has attracted interest as a stable genetic trait potentially associated with inter-individual variability in ageing-related outcomes. This narrative review critically examines current evidence linking ABO blood groups to age-related diseases and biological mechanisms of ageing. A structured search of major biomedical databases was performed, focusing primarily on studies published in the last five years and complemented by seminal earlier reports. Current findings indicate associations between ABO phenotypes and several chronic conditions, including cardiovascular disease, thrombotic disorders, diabetes, cancer, allergies, and cognitive disorders, which substantially contribute to morbidity and mortality in older adults. However, data are contradictory and dependent on ethnicity, genetic background and environmental factors. Non-O blood groups consistently exhibit a higher risk of thrombotic and cardiovascular events, likely mediated by differences in coagulation factors, endothelial function, and hemostatic balance. ABO-related phenotypic variation may also influence processes implicated in ageing, including vascular dysfunction, chronic low-grade inflammation, immune remodeling, glycosylation pathways, cellular senescence, and host-microbiome interactions. However, evidence supporting a direct relationship between ABO blood groups and longevity remains inconsistent and appears to be population dependent. Overall, current data suggest that ABO blood groups are unlikely to represent independent biomarkers of ageing, but rather modest, context-dependent modifiers of biological pathways contributing to susceptibility to age-related diseases. Further longitudinal and mechanistic studies are needed to clarify their role in healthy and pathological ageing trajectories. SUMMARY: ABO blood group system has been associated with susceptibility to several age-related diseases (ARDs). Non-O blood groups show a higher risk of thrombotic and cardiovascular events. Although some studies also suggest a relationship between ABO phenotype and longevity, findings remain inconsistent and appear to vary across populations. Potential mechanisms linking ABO blood groups to ageing include effects on inflammation, vascular function, immune responses, and host-microbiome interactions. Overall, current evidence indicates that ABO blood group is unlikely to represent an independent biomarker of ageing, but rather a modest and context-dependent factor that can influence aging-related mechanisms and contribute to the ARD development.

Coronary microvascular dysfunction plays a central role in major cardiovascular diseases, yet non-invasive imaging of the human coronary microcirculation remains an unresolved challenge in clinical practice. Ultrasound Localization Microscopy (ULM) enables microvascular imaging beyond the diffraction limit, but whole-heart volumetric ULM is hindered by cardiac motion, rib-induced acoustic aberrations, limited control over microbubble (MB) dynamics, and hardware-related field-of-view constraints. Experimental optimization under clinical conditions is therefore challenging.

We developed a dedicated simulation framework for three-dimensional coronary ULM by extending a previously validated brain ULM simulation framework to the human coronary circulation. A synthetic coronary vascular network with physiologically realistic hemodynamics was generated using a space-colonization algorithm combined with Murray's law and Poiseuille flow assumptions. Ground-truth MB dynamics were simulated and convolved with experimentally measured in vitro point spread functions, including configurations with human ribs to reproduce acoustic aberrations. The framework generates realistic four-dimensional (x, y, z, t) ultrasound datasets for quantitative benchmarking of MB detection, localization, and tracking performance.

Systematic simulations demonstrated that both cardiac motion and rib-induced aberrations significantly degrade coronary ULM performance, particularly in small vessels, leading to reduced precision, sensitivity, and Jaccard index. Cardiac gating partially restored performance but increased acquisition time, underscoring critical trade-offs between robustness and efficiency.

This simulation framework provides a realistic and flexible benchmarking platform for the evaluation of volumetric coronary ULM under controlled conditions. It enables quantitative assessment of acquisition strategies, probe designs and image-processing algorithms, thereby supporting the development and clinical translation of three-dimensional coronary ULM.

Postoperative cognitive dysfunction (POCD) is a common complication following aortic arch replacement. This study aimed to identify risk factors for early POCD in patients undergoing aortic arch replacement and determine the effect of POCD on long-term survival.

In this prospective cohort study, 103 patients who underwent aortic arch replacement for complex aortic arch diseases were enrolled. Cognitive function was assessed preoperatively and on postoperative days 5 to 7 using the Montreal Cognitive Assessment. POCD was defined as a ≥20% decline in total score compared with baseline.

The incidence of POCD was 15.5%. Compared with the non-POCD group, patients with POCD were significantly older (62 ± 13 vs. 52 ± 13, p = 0.008), had a higher proportion of females (68.8 vs. 37.9%, p = 0.044), and experienced greater intraoperative blood loss (751 ± 165 vs. 667 ± 122 mL; p = 0.018). Postoperative adverse events were similar between the two groups. Significant declines were observed in the domains of visuospatial/executive function (p = 0.003), attention/concentration/working memory (p < 0.001), and orientation (p = 0.002). Multivariable logistic regression analysis identified age, female sex, and antegrade cerebral perfusion (ACP) time as independent risk factors for POCD. Midterm survival was similar between POCD and non-POCD groups (1-year survival: 100 vs. 95.2%; p = 0.437).

POCD remains a common complication after aortic arch replacement. Advanced age, female sex, and prolonged ACP time are independent predictors of POCD. POCD was not associated with worse midterm survival. These findings may help preoperative risk stratification and optimization of intraoperative management.

Micro- and nanoplastics (MNPs) are emerging risk factors for cardiovascular diseases. The present study aimed to evaluate the burden of MNPs in coronary blood across the spectrum of coronary artery disease (CAD), and their association with air pollution exposure and inflammation.

Cross-sectional study, including 61 consecutive patients undergoing coronary angiography for suspected CAD, stratified into: ST-segment elevation myocardial infarction (STEMI, n = 19), chronic coronary syndromes (CCS, n = 20), and controls with normal coronary arteries (n = 22). MNPs were quantified in coronary and peripheral blood using pyrolysis-gas chromatography-mass spectrometry and laser direct infrared spectroscopy. Air pollution exposure data were collected on the day of the invasive procedure (acute exposure) and over the preceding 2 years (chronic exposure).

MNPs were detected significantly more frequently in STEMI patients (84.2%) than in CCS (40%) and controls (31.8%) (P = .002), with higher concentration and greater polymer diversity [median of 3 polymers (interquartile range: 2-4), P < .001]. Polyethylene was the predominant polymer (97%). The same polymers were consistently identified in peripheral and coronary blood samples from individual patients, with the highest concentrations in coronary blood (P < .001). STEMI patients showed higher levels of interleukin-6 and tumour necrosis factor-α (P≤.006) and were exposed to higher levels of PM2.5 (P≤.012). MNP detection was more frequent among smokers and patients exposed to PM2.5 > 15 µg/m3 (P = .006), with all patients presenting both factors showing detectable MNPs (P < .001). In multivariable analysis, smoking history emerged as the only independent predictor of MNP presence (odds ratio 5.69, 95% confidence interval 1.33-26.63, P = .023).

STEMI patients exhibited a greater burden of MNPs in coronary blood than CCS and controls. MNP detection frequently co-occurred with elevated inflammatory biomarkers, greater PM2.5 exposure, and smoking, suggesting a potential association between environmental exposure and CAD.

IgA nephropathy (IgAN) has diverse clinical presentations and responses to treatment. For systemic corticosteroids in particular, randomised controlled trials have reported conflicting effects, highlighting the need for individualised treatment strategies.

In this retrospective cohort study, we derived and validated a causal machine learning (ML) framework to estimate individualised corticosteroid treatment effects in IgAN. Eight international cohorts, including the VALIGA, CureGN, and NURTuRE-CKD repositories, comprising 1022 patients, were analysed (derivation, n = 464; validation, n = 558). We integrated baseline clinical data, histopathological classification scores (MEST-C), and deep learning-based histomorphological biomarkers (pathomics) from digitised kidney biopsies. The framework estimated the effect of systemic corticosteroids on the composite endpoint of a ≥50% decline in estimated glomerular filtration rate or kidney failure within five years of biopsy.

Across the overall study population, systemic corticosteroid therapy was not associated with a significant improvement in the composite outcome (p = 0·27). However, the causal ML framework revealed substantial treatment heterogeneity, identifying patients with high predicted benefit who achieved longer progression-free survival with corticosteroids (0·43 years, 95% CI 0·18-0·73, p < 0·01), while no benefit was observed in those with low predicted benefit (-0·005 years, 95% CI -0·3 to 0·22, p > 0·05). An individualised framework-guided treatment assignment was estimated to reduce systemic corticosteroid use by 60·7%. Pathomics facilitated the identification of interstitial inflammation and tubulitis as key features of corticosteroid response.

This study demonstrates that a causal ML framework integrating clinical, histopathological, and pathomics predictors can individualise treatment assignments for systemic corticosteroids in IgAN. This approach provides a blueprint for precision therapy in IgAN, supporting AI-enhanced clinical decision-making in the era of emerging targeted treatments.

German Research Foundation; European Research Council; German Federal Ministry of Education and Research; German Innovation Fund of the Federal Joint Committee; Clinician Scientist Program of the Faculty of Medicine RWTH Aachen University.

Evidence regarding the combined association of the visceral adiposity index (VAI), an indicator of visceral fat distribution and dysfunction, and handgrip strength with cardiovascular disease (CVD) remains limited. This study aimed to examine the association of VAI and/or handgrip strength with CVD among middle-aged and older adults.

A total of 6967 participants free of CVD at baseline were included from the China Health and Retirement Longitudinal Study. The primary outcome was incident CVD. Cox proportional hazards models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

The mean age of the study was 58.6 (9.2) years and 3677 (52.8%) were female. Over a median follow-up of 8.9 years, 1539 (22.1%) participants developed CVD. Compared with participants in the lowest VAI quartile (<2.04), those in quartiles 2-4 (≥2.04) had significantly higher risks of CVD (HR, 1.36; 95%CI: 1.16-1.61), heart disease (HR, 1.28; 95%CI: 1.09-1.50), and stroke (HR, 1.82; 95%CI: 1.39-2.39). When handgrip strength was assessed as sex-specific quartiles, compared with participants in the quartile 1-2, those in quartiles 3-4 had lower risks of CVD (HR, 0.83; 95%CI: 0.74-0.92), heart disease (HR, 0.82; 95%CI: 0.72-0.93), and stroke (HR, 0.81; 95%CI: 0.66, 1.00). Jointly, the highest risk of CVD was observed in participants with higher VAI (≥2.04) and lower handgrip strength (the quartile 1-2) (HR, 1.51; 95%CI:1.24-1.85).

High VAI and low handgrip strength were independently associated with increased CVD risk. Participants with combined phenotype of high VAI and low handgrip strength had the highest CVD risk.

Lanthanide-doped upconversion nanoparticles (UCNPs) due to their unique optical properties are promising for applications ranging from bioimaging to biosensing. However, their practical implementation remains challenging owing to relatively low luminescence efficiency. Herein, we synthesize a series of Ce-doped Yb/Eu/ZnO, Yb/Er/ZnO and Yb/Tm/ZnO UCNPs via a hydrothermal method. Ce ions incorporation promotes anisotropic growth, which increases surface roughness and modulates the local coordination environment. Electrochemical impedance spectroscopy and Tafel plot analyses reveal that Ce doping significantly enhances charge separation and transfer kinetics. Ce ion doping markedly increases the emission intensities of Eu³⁺, Er³⁺ and Tm³⁺, attributed to the formation of Yb³⁺ dimers and efficient energy transfer under 980 nm excitation. Benefiting from these improvements, the Ce-doped ZnO UCNPs exhibit three distinct bio-applications: (i) superior low-temperature optical thermometry with a maximum relative sensitivity of 4.81% K^-1 at 80 K; (ii) excellent antibacterial activity against S. aureus and E. coli (up to 82.16% and 87.64% inhibition at 8 mol% Ce); and (iii) successful employment as luminescent probes in a multiplex immunoassay for the cardiac markers BNP (detection range 10-100 pg/mL) and ST2 (5-25 ng/mL), with high specificity and sensitivity. These findings underscore the potential of Ce-doped ZnO UCNPs as multifunctional platforms for optical thermometry, antibacterial therapy and biomedical diagnostics.

Hemostatic control in neurosurgery represents a major clinical challenge, in which even small variations in blood loss can critically alter intracranial pressure and neurological prognosis. Fibrinogen, the first coagulation factor to be depleted during hemorrhage, is also an early marker of coagulopathy and a key determinant of clot stability. This narrative review analyzed the scientific literature published between 2020 and 2025 in PubMed, Scopus, and the Cochrane Library, with emphasis on studies evaluating the pathophysiology, diagnosis, and targeted replacement of fibrinogen in neurosurgical patients. Through critical analysis and systematic integration of the selected studies, convergent evidence was identified demonstrating that low fibrinogen levels are associated with greater blood loss, an increased risk of intracranial rebleeding, and poorer functional outcomes. Viscoelastic test-guided administration allows dose optimization and reduction of transfusion requirements, while empirical strategies based on serum concentrations and surgical context provide safe alternatives when such technologies are unavailable. Understanding when and how to replace fibrinogen constitutes an essential component of comprehensive patient blood management in neurosurgery. This paradigm, summarized by the principle "think, assess, and replace", consolidates an integrated model of goal-directed neurohemostasis.