Explore the vast range of titles available.

Cardiovascular disease (CVD) and neoplasms are the two leading causes of death worldwide. Previous research has predominantly addressed these conditions separately or focused on specific regions. We aimed to characterize the global co-occurrence pattern of CVD and neoplasms from spatial and temporal perspectives and identify corresponding risk factors across different epidemiological contexts. Using GBD 2021 data, we extracted age-standardized disability-adjusted life year (DALY) rates of CVD and neoplasms and modifiable risk factor exposure from 204 countries and territories (1990-2021). We identified four epidemiological patterns: low-burden, neoplasm-dominant, CVD-dominant, and dual-burden regions. We calculated population attributable fractions (PAF) and integrated machine learning with SHAP values to distinguish intervention priorities. Average annual percentage changes (AAPC) were used to evaluate temporal trends. Each pattern comprised 50-52 countries. Spatial distribution overlapped with socioeconomic development stages and risk factor exposure. Temporal analysis revealed widening global inequality: low-burden regions achieved 3-4% annual reductions while dual-burden regions experienced an increasing burden, creating a 5.8 percentage point gap. High systolic blood pressure was the universal dominant CVD risk factor, accounting for 49.7% of the global burden (49.2-52.4% across patterns). For neoplasms, smoking contributed 18.5% globally but varied dramatically by pattern (10.4-23.4%). Modifiable risk factors' specific combinations greatly influenced global disparities. The co-occurrence of CVD and neoplasms represents interconnected manifestations of different epidemiological transition stages, with concerning divergence between regions. Interventions targeting hypertension control and tobacco cessation, combined with pattern-specific strategies, can fundamentally reduce the global disease burden.

Diabetes mellitus (DM) is a serious epidemic around the globe, and cardiovascular diseases account for the majority of deaths in patients with DM. Diabetic cardiomyopathy (DCM) is defined as a cardiac dysfunction derived from DM without the presence of coronary artery diseases and hypertension. Patients with either type 1 or type 2 DM are at high risk of developing DCM and even heart failure. Metabolic disorders of obesity and insulin resistance in type 2 diabetic environments result in dyslipidaemia and subsequent lipid‐induced toxicity (lipotoxicity) in organs including the heart. Although various mechanisms have been proposed underlying DCM, it remains incompletely understood how lipotoxicity alters cardiac function and how DM induces clinical heart syndrome. With recent progress, we here summarize the latest discoveries on lipid‐induced cardiac toxicity in diabetic hearts and discuss the underlying therapies and controversies in clinical DCM.

Doxorubicin (DOX)‐induced cardiotoxicity (DoIC) is a major side effect for cancer patients. Recently, ferroptosis, triggered by iron overload, is demonstrated to play a role in DoIC. How iron homeostasis is dysregulated in DoIC remains to be elucidated. Here, the authors demonstrate that DOX challenge exhibits reduced contractile function and induction of ferroptosis‐related phenotype in cardiomyocytes, evidenced by iron overload, lipid peroxide accumulation, and mitochondrial dysfunction. Compared to Ferric ammonium citrate (FAC) induced secondary iron overload, DOX‐challenged cardiomyocytes show a dysfunction of iron homeostasis, with decreased cytoplasmic and mitochondrial iron–sulfur (FeS) cluster‐mediated aconitase activity and abnormal expression of iron homeostasis–related proteins. Mechanistically, mass spectrometry analysis identified DOX‐treatment induces p53‐dependent degradation of Parkinsonism associated deglycase (Park7) which results in iron homeostasis dysregulation. Park7 counteracts iron overload by regulating iron regulatory protein family transcription while blocking mitochondrial iron uptake. Knockout of p53 or overexpression of Park7 in cardiomyocytes remarkably restores the activity of FeS cluster and iron homeostasis, inhibits ferroptosis, and rescues cardiac function in DOX treated animals. These results demonstrate that the iron homeostasis plays a key role in DoIC ferroptosis. Targeting of the newly identified p53–Park7 signaling axis may provide a new approach to prevent DoIC. Ferroptosis is demonstrated to play a role in doxorubicin (DOX)‐induced cardiotoxicity (DoIC). This study shows that upon DOX challenge, myocardial Park7, which binds to FeS clusters and acts upstream of the iron homeostasis pathway, is degraded in a p53‐dependent manner and results in iron homeostatic dysregulation. The novel pathway proposes a new perspective on the pathogenesis of DoIC.

Diabetic cardiomyopathy (DbCM) is characterized by diastolic dysfunction, which progresses into heart failure and aberrant electrophysiology in diabetic patients. Dyslipidemia in type 2 diabetic patients leads to the accumulation of lipid droplets (LDs) in cardiomyocytes and results in lipid toxicity which has been suggested to drive DbCM. It is aimed to explore potential pathways that may boost LDs degradation in DbCM and restore cardiac function. LDs accumulation resulted in an increase in lipid toxicity in DbCM hearts is confirmed. Microlipophagy pathway, rather than traditional macrolipophagy, is activated in DbCM hearts. RNA‐Seq data and Rab7‐CKO mice implicate that Rab7 is a major modulator of the microlipophagy pathway. Mechanistically, Rab7 is phosphorylated at Tyrosine 183, which allows the recruitment of Rab‐interacting lysosome protein (Rilp) to proceed LDs degradation by lysosome. Treating DbCM mice with Rab7 activator ML‐098 enhanced Rilp level and rescued the observed cardiac dysfunction. Overall, Rab7‐Rilp‐mediated microlipophagy may be a promising target in the treatment of lipid toxicity in DbCM is suggested. How cardiomyocytes digest excessive lipid droplets and overcome lipid toxicity in diabetic cardiomyopathy remains unknown. Rab7‐Rilp axis‐mediated microlipophagy is activated in diabetic cardiomyocytes to facilitate lipid droplets degradation, ameliorate lipid toxicity, and protect the heart. Treating mice with Rab7 activator ML‐098 enhances Rilp level and rescues cardiac dysfunction in diabetic cardiomyopathy.

Background Adipose tissue homeostasis is at the heart of many metabolic syndromes such as diabetes. Previously it has been demonstrated that adipose tissues from diabetic patients are senescent but whether this contributes to diabetic cardiomyopathy (DCM) remains to be elucidated. Methods The streptozotocin (STZ) type 1 diabetic mice were established as animal model, and adult mouse ventricular myocytes (AMVMs) isolated by langendorff perfusion as well as neonatal mouse ventricular myocytes (NMVMs) were used as cell models. Senescent associated β galactosidase (SA-β-gal) staining and RT-qPCR were used to identify the presence of adipose senescence in diabetic adipose tissue. Senescent adipose were removed either by surgery or by senolytic treatment. Large extracellular vesicles (LEVs) derived from adipose tissue and circulation were separated by ultracentrifugation. Cardiac systolic and diastolic function was evaluated through cardiac ultrasound. Cardiomyocytes contraction function was evaluated by the Ionoptix HTS system and live cell imaging, mitochondrial morphology and functions were evaluated by transmission electron microscope, live cell fluorescent probe and seahorse analysis. RNA-seq for AMVMs and miRNA-seq for LEVs were performed, and bioinformatic analysis combined with RT-qPCR and Western blot were used to elucidate underlying mechanism that senescent adipose derives LEVs exacerbates myocardial metabolism. Results SA-β-gal staining and RT-qPCR identified the presence of adipose tissue senescence in STZ mice. Through surgical as well as pharmacological means we show that senescent adipose tissue participates in the pathogenesis of DCM in STZ mice by exacerbates myocardial metabolism through secretion of LEVs. Specifically, expression of miRNA-326-3p was up-regulated in LEVs isolated from senescent adipose tissue, circulation, and cardiomyocytes of STZ mice. Up-regulation of miRNA-326-3p coincided with myocardial transcriptomic changes in metabolism. Functionally, we demonstrate that miRNA-326-3p inhibited the expression of Rictor and resulted in impaired mitochondrial and contractile function in cardiomyocytes. Conclusion We demonstrate for the first time that senescent adipose derived LEVs exacerbates myocardial metabolism through up-regulated miRNA-326-3p which inhibits Rictor in cardiomyocytes. Furthermore, reducing senescence burden in adipose tissue is capable of relieving myocardial metabolism disorder in diabetes mellitus.

Background: Cardiovascular adverse events represent critical complications of antineoplastic therapy with profound implications for cancer survivorship and treatment outcomes. Despite the clinical significance, comprehensive pharmacovigilance data characterizing distinctive cardiotoxicity profiles across modern cancer therapeutics remain limited. Objectives: This investigation systematically analyzes cardiotoxicity patterns associated with antineoplastic agents using the FDA Adverse Event Reporting System (FAERS) database to inform evidence-based cardiovascular monitoring strategies. Design: A retrospective pharmacovigilance study utilizing disproportionality analysis and time-to-onset evaluation. Methods: We conducted a comprehensive analysis of FAERS data spanning 2004–2024, employing validated disproportionality metrics including reporting odds ratio (ROR) and proportional reporting ratio (PRR) to detect significant drug-event associations. Advanced time-to-onset analysis revealed temporal patterns of cardiotoxicity development across therapeutic classes. Statistical significance was defined as ROR >1 with 95% confidence intervals excluding 1.0, and PRR >2 with chi-square >4. Results: Analysis of 18,289,374 reports identified 51,402 cases of antineoplastic-related cardiovascular toxicity, demonstrating distinct class-specific patterns. Anthracyclines exhibited profound associations with structural cardiac damage (doxorubicin-cardiomyopathy: ROR = 20.64, 95% CI: 19.87–21.45). Immune checkpoint inhibitors demonstrated unprecedented immune-mediated cardiac inflammation (pembrolizumab-myocarditis: ROR = 245.36, 95% CI: 218.42–275.88). Fluoropyrimidines showed distinctive vasospastic effects (5-fluorouracil-Prinzmetal angina: ROR = 18.27, 95% CI: 14.72–22.69). Critical temporal patterns emerged: fluoropyrimidines caused early-onset cardiotoxicity (median: 11 days, IQR: 4–28), anthracyclines showed intermediate onset (doxorubicin median: 64 days, IQR: 21–156; epirubicin median: 72 days, IQR: 28–168), while mitoxantrone demonstrated delayed effects (median: 457 days, IQR: 182–891). Cardiogenic shock emerged as the most lethal manifestation with a 43.08% mortality rate (95% CI: 40.12–46.14). Conclusion: This landmark pharmacovigilance study reveals previously uncharacterized temporal and mechanistic patterns of antineoplastic cardiotoxicity, providing an essential evidence-based framework for cardiovascular monitoring strategies. The findings highlight critical intervention windows: immediate monitoring for fluoropyrimidines, intermediate surveillance for anthracyclines (2–6 months), and extended follow-up for agents like mitoxantrone (>12 months). These insights support the development of risk-stratified cardio-oncology protocols tailored to specific therapeutic classes. Plain language summary Heart problems from cancer drugs: a large-scale safety study using FDA reports Cancer treatments can sometimes cause serious heart problems, but doctors need better information about which drugs cause which heart issues and when they occur. This study looked at over 18 million safety reports sent to the FDA between 2004 and 2024 to understand patterns of heart problems caused by cancer drugs. The researchers found more than 51,000 reports of heart problems linked to cancer medications. Different types of cancer drugs caused different heart problems at different times: • Anthracyclines (like doxorubicin) - older chemotherapy drugs that can permanently damage the heart muscle, typically causing problems after 2-5 months of treatment • Immune checkpoint inhibitors (like pembrolizumab) - newer immunotherapy drugs that can cause dangerous heart inflammation, often within the first few weeks • Fluoropyrimidines (like 5-fluorouracil) - drugs that can cause heart artery spasms, usually within the first 1-4 weeks • Mitoxantrone - a drug that can cause heart problems much later, often after more than a year The study found that cardiogenic shock (when the heart can’t pump enough blood) was the most dangerous heart problem, with nearly half of patients dying from it. These findings help doctors know when to watch patients most carefully for heart problems. For example, patients getting fluoropyrimidines need immediate heart monitoring, while those getting anthracyclines need regular heart checks for several months, and patients on mitoxantrone need long-term follow-up for over a year.

Hyperuricemia is associated with poor clinical outcomes in several cardiovascular diseases, including heart failure (HF). However, whether lowering serum uric acid (SUA) levels improves the prognosis of HF remains insufficiently studied. To evaluate whether urate-lowering therapy (ULT) with febuxostat confers clinical benefits in patients with HF and concomitant hyperuricemia. Prospective, observational cohort study. Patients with chronic HF and hyperuricemia were enrolled and assigned either to a febuxostat group or to a non-ULT group and were followed prospectively for 5 years. The primary endpoint was all-cause mortality or rehospitalization for HF. Among 2005 patients, those with higher SUA levels experienced more endpoint events. After propensity score matching, we found that febuxostat therapy significantly reduced the incidence of primary endpoints in patients with HF with preserved ejection fraction (HFpEF) [ = 0.012; hazard ratios (HR), 0.744; 95% confidence intervals (CI), 0.589-0.939], but not in those with HF with reduced ejection fraction (HFrEF) or mildly reduced ejection fraction (HFmrEF) ( = 0.234; HR, 0.894; 95% CI, 0.742-1.077). The benefits of febuxostat in HFpEF were most evident in patients within the highest tertiles of B-type natriuretic peptide (BNP) ( = 0.021; HR, 0.647; 95% CI, 0.436-0.960) and SUA ( = 0.025; HR, 0.651; 95% CI, 0.441-0.963). High SUA levels are associated with increased all-cause mortality and rehospitalization for HF. Febuxostat-mediated SUA reduction significantly improved clinical outcomes in patients with HFpEF, particularly those with elevated SUA and BNP levels.

Arrhythmias and major adverse cardiac events remain significant complications following ST-segment elevation myocardial infarction (STEMI). Shenfu injection, a traditional Chinese medicine formulation, has shown cardioprotective effects in preclinical studies. This trial is aimed at investigating whether Shenfu injection as an adjunctive therapy to standard treatment could reduce arrhythmias and improve clinical outcomes in patients with STEMI undergoing percutaneous coronary intervention (PCI). A single-center, prospective, randomized, controlled trial was conducted at Shanghai Ninth People's Hospital among 245 patients with STEMI undergoing PCI. Participants were randomized to receive either standard therapy plus Shenfu injection (50 mL, administered intravenously twice daily for five consecutive days) ( = 123) or standard therapy alone ( = 122). The primary endpoint was the incidence of in-hospital arrhythmias. Secondary endpoints included major adverse cardiac events (MACEs) during the 12-month follow-up period and cardiac magnetic resonance imaging parameters. A total of 245 patients underwent randomization (123 assigned to Shenfu injection group and 122 assigned to control group). During hospitalization, patients assigned to Shenfu injection had a significantly lower incidence of arrhythmias compared with the control group (24.4% vs. 38.5%, = 0.017), with the most pronounced effect on frequent ventricular premature contractions (7.3% vs. 15.5%, = 0.042). After adjustment for key baseline covariates including age, coronary artery disease extent, myocardial injury markers (CK-MB max and TNI max), left ventricular ejection fraction, B-type natriuretic peptide, door-to-balloon time, hypertension, and diabetes mellitus, Shenfu injection remained independently associated with reduced risk of in-hospital arrhythmias (adjusted OR 0.454, 95% CI: 0.249-0.827, = 0.010). Cardiac magnetic resonance imaging performed in 174 patients revealed significantly smaller infarct size (16.1 ± 9.1 vs. 20.8 ± 13.1 g, = 0.007) and lower incidence of microvascular obstruction (45.0% vs. 65.0%, = 0.008) in the Shenfu group, with both parameters showing significant positive correlations with arrhythmia occurrence. During the 12-month follow-up, patients receiving Shenfu injection had a higher event-free rate from MACEs compared with the control group (12-month Kaplan-Meier event-free rate estimates, 84.6% vs. 73.0%, respectively; = 0.028). Treatment with Shenfu injection as an adjunctive therapy to standard treatment in patients with STEMI undergoing PCI significantly reduced in-hospital arrhythmias, infarct size, microvascular obstruction, and major adverse cardiac events during a 12-month follow-up period. The independent effect on arrhythmias after comprehensive statistical adjustment and the demonstrated correlation between reduced myocardial damage and arrhythmia prevention suggest the potential therapeutic value of Shenfu injection in improving both short-term and long-term outcomes in STEMI patients. Chinese Clinical Trial Registry Identifier: ChiCTR2200066918.

Germanium (Ge) has long been regarded as a promising channel material, owing to its superior carrier mobility and highly tunable electronic band structure. The new generation of low-power electronics is approaching the formation of fully depleted (FD) transistors on Si-on-insulator (SOl) and Ge-on-insulator (GOl) substrates. In this work, we present a full process of a novel FDGOI transistor formed on a strained GOI with low defect density. This scalable and industry-compatible approach enables the formation of uniform 50 nm thick Ge layers by using spinning wet etch with ultrasmooth surfaces (RMS roughness = 0.262 nm) and a low etch-pit density of ~105 cm−2. Electrical measurements reveal excellent carrier transport properties, with back-gate (BG) transistors achieving mobilities of 550–600 cm2/V·s, while front-gate (FG) devices exhibit sharp switching behavior and steep subthreshold slopes, yielding ION/IOFF ratios up to 105. Temperature-dependent measurements further demonstrate a pronounced enhancement of device performance: the ION/IOFF ratio increases to 106, the subthreshold swing (SS) decreases from 179 mV/dec at room temperature to 137 mV/dec at 120 K, and the threshold-voltage shift with temperature is as low as 1.87 mV/K across the range of 30–300 K. Such behavior highlights the potential of band-gap engineering for precise threshold-voltage control. Taken together, these results establish GOI as a CMOS-compatible material platform and provide a solid technological basis for the development of next-generation low-power transistors beyond conventional CMOS scaling.

Importance Lower extremity peripheral arterial disease (PAD) is a significant health concern among older adults globally, affecting both mortality and quality of life. Objective To evaluate the temporospatial trends and its risk factors in lower extremity PAD-related burden among adults aged 60 years and older from 1990 to 2021. Design, setting, and participants This repeated cross-sectional study utilized data from the Global Burden of Disease Study 2021, encompassing 204 countries and territories. The study population included adults aged 60 years and older. Exposure Lower extremity PAD among older adults from January 1990 to December 2021. Main outcomes and measures Primary outcomes included age-standardized prevalence rates (ASPR), mortality rates (ASMR), disability-adjusted life-years (DALYs), and average annual percentage changes (AAPCs). Trends were analyzed by age, sex, and sociodemographic index (SDI). Joinpoint regression analysis was used to identify significant trend changes. Results From 1990 to 2021, global trends showed decreases in lower extremity PAD-related prevalence, mortality, and DALYs. Significant geographical disparities were observed: high-SDI regions had the highest prevalence (11,171.66 per 100,000 in 2021) but showed declining trends (AAPC, -0.74; 95% CI, -0.80 to -0.68), while low-SDI regions had the lowest prevalence (4,842.40 per 100,000) but demonstrated increasing trends (AAPC, 0.22; 95% CI, 0.21 to 0.24). Regionally, although lower extremity PAD-related prevalence showed a decreasing trend in most regions from 1990 to 2021, there were still some regions with an increasing trend (North Africa and Middle East AAPC, 0.57; 95% CI, 0.55 to 0.59). Temporal analysis showed sex-specific divergent trends in recent years, with males exhibiting an upward trend since 2015 (APC, 0.15; 95% CI, 0.07 to 0.24), while females showed a slowed decline since 2014 (APC, -0.06; 95% CI, -0.12 to -0.01). Decomposition analysis identified population growth as the primary driver of PAD burden increase, with epidemiological changes showing contrasting effects across SDI regions. Among risk factors, high fasting glucose emerged as the leading contributor, while smoking’s contribution decreased. Conclusions and relevance This study revealed significant disparities in lower extremity PAD burden across different SDI levels and regions, with low-SDI countries facing an increasing burden. The contrasting trends between high- and low-SDI regions, coupled with varying risk factor patterns (particularly the rise in high fasting glucose and decline in smoking), suggest the need for targeted interventions in resource-limited settings to address this growing health challenge among older adults. Key points Question What are the trends in the burden of lower extremity PAD among older adults at the global, regional, and sociodemographic index subgroup levels from 1990 to 2021? Finding In this cross-sectional study among older adults, although lower extremity PAD prevalence (measured per 100000 population) decreased from 9525.09 to 8220.21 from 1990 to 2021, divergent trends were observed with high-SDI countries showing decline while low-SDI countries demonstrated increases. Population growth was the primary driver of PAD burden globally, while risk factor patterns varied significantly, with high fasting glucose emerging as the leading risk factor and smoking showing substantial decline. Meaning The lower extremity PAD burden among older adults shows significant disparities across SDI regions, highlighting the need to address healthcare inequities and strengthen preventive measures in low-SDI countries. The changing patterns of risk factors underscore the importance of targeted interventions and comprehensive disease management strategies across different socioeconomic settings.