Search Results (7,827)

Circulating heart-reactive autoantibodies (aAbs) detected in a variety of heart diseases (e.g., myocarditis, dilated cardiomyopathy, and myocardial infarction) have been associated with the progression of heart failure and a poor prognosis. However, the underlying mechanisms remain largely unknown. We investigated the effects of murine plasma containing aAbs against cardiac troponin I (cTnI) on neonatal rat cardiomyocytes (NRCMs). An autoimmune response to cTnI in A/J mice was induced, and anti-cTnI-aAbs were quantified. After 21 days, cardiac function, inflammation, fibrosis, and apoptosis were evaluated. In complementary in vitro liquid biopsy experiments, NRCMs were incubated with murine plasma containing high anti-cTnI-aAb levels or corresponding controls. Morphological phenotyping was performed using the C-MORE fluorescent image-based analysis workflow. Immunization with cTnI resulted in high anti-cTnI-aAb production, followed by myocardial inflammation, fibrosis, and impaired ejection fraction. NRCMs exposed to anti-cTnI-aAb-containing plasma showed reduced cell size, altered shape and radius, and elevated rate of dead cells in cell cycle analysis (p < 0.01, for 20% plasma). Together, these findings suggest a direct interaction of anti-cTnI-aAbs on cardiomyocytes, likely promoting adverse myocardial remodeling in vivo. Full article

The prediction of Remaining Useful Life (RUL) constitutes a vital aspect of Prognostics and Health Management (PHM), providing capabilities for the assessment of mechanical component health status and prediction of failure instances. Recent studies on feature extraction, time-series modeling, and multi-task learning have shown remarkable advancements. However, most deep learning (DL) techniques predominantly focus on unimodal data or static feature extraction techniques, resulting in a lack of RUL prediction methods that can effectively capture the individual differences among heterogeneous sensors and failure modes under complex operational conditions. To overcome these limitations, an adaptive RUL prediction framework named ADAPT-RULNet is proposed for mechanical components, integrating the feature extraction capabilities of attention-enhanced deep learning (DL) and the decision-making abilities of deep reinforcement learning (DRL) to achieve end-to-end optimization from raw data to accurate RUL prediction. Initially, Functional Alignment Resampling (FAR) is employed to generate high-quality functional signals; then, attention-enhanced Dynamic Time Warping (DTW) is leveraged to obtain individual degradation stages. Subsequently, an attention-enhanced of hybrid multi-scale RUL prediction network is constructed to extract both local and global features from multi-format data. Furthermore, the network achieves optimal feature representation by adaptively fusing multi-source features through Bayesian methods. Finally, we innovatively introduce a Deep Deterministic Policy Gradient (DDPG) strategy from DRL to adaptively optimize key parameters in the construction of individual degradation stages and achieve a global balance between model complexity and prediction accuracy. The proposed model was evaluated on aircraft engines and railway freight car wheels. The results indicate that it achieves a lower average Root Mean Square Error (RMSE) and higher accuracy in comparison with current approaches. Moreover, the method shows strong potential for improving prediction accuracy and robustness in varied industrial applications. Full article

MicroRNAs (miRNAs) are critical regulators of gene expression in cancer biology and cardiovascular disease. miR-106b-5p, a member of the miR-106b-25 cluster, has been widely studied for its oncogenic activity in various malignancies. However, its role as a direct molecular driver of anthracycline-induced cardiotoxicity has only recently been uncovered. This finding highlights new therapeutic possibilities at the intersection of oncology and cardiovascular medicine. This review outlines the dual role of miR-106b-5p as a key modulator in both tumor progression and chemotherapy-induced cardiac dysfunction. miR-106b-5p is upregulated in numerous cancers—including breast, prostate, lung, gastric, colorectal, hepatocellular, and esophageal—and promotes tumorigenesis via suppression of tumor suppressors such as PTEN, BTG3, p21, and SMAD7, leading to activation of oncogenic pathways like PI3K/AKT and TGF-β. Importantly, we present the first evidence that miR-106b-5p is significantly upregulated in the myocardium in response to doxorubicin treatment, where it drives left ventricular dysfunction by targeting PR55α, a key regulator of PP2A activity. This pathway results in cytoplasmic HDAC4 accumulation, aberrant activation of the YY1 transcription factor, and upregulation of sST2, a biomarker linked to adverse cardiac remodeling and poor prognosis. In response, we developed AM106, a novel locked nucleic acid antagomir that silences miR-106 b-5p. Preclinical studies demonstrate that AM106 restores PR55α/PP2A activity, reduces sST2 expression, and prevents structural and functional cardiac damage without compromising anti-tumor efficacy. In parallel, artificial intelligence (AI) tools could be leveraged in the future—based on established AI applications in miRNA cancer research—to accelerate the identification of miR-106b-5p-related biomarkers and guide personalized therapy selection. Our findings position miR-106b-5p as a previously unrecognized molecular bridge between cancer and doxorubicin-induced cardiotoxicity. The development of the AM106 antagomir represents a promising approach with potential clinical applicability in cardio-oncology, offering dual benefits: tumor control and cardioprotection. Coupling this innovation with AI-driven analysis of patient data may enable precision risk stratification, early intervention, and improved outcomes. miR-106b-5p thus emerges as a central therapeutic target and biomarker candidate for transforming the clinical management of cancer patients at risk for heart failure. Full article

To address the failure of unmanned aerial vehicle (UAV) target tracking caused by occlusion and limited field of view in dense low-altitude obstacle environments, this paper proposes a novel framework integrating occlusion-aware modeling and multi-UAV collaboration. A lightweight tracking model based on the Mamba backbone is developed, incorporating a Dilated Wavelet Receptive Field Enhancement Module (DWRFEM) to fuse multi-scale contextual features, significantly mitigating contour fragmentation and feature degradation under severe occlusion. A dual-branch feature optimization architecture is designed, combining the Distilled Tanh Activation with Context (DiTAC) activation function and Kolmogorov–Arnold Network (KAN) bottleneck layers to enhance discriminative feature representation. To overcome the limitations of single-UAV perception, a multi-UAV cooperative system is established. Ray intersection is employed to reduce localization uncertainty, while spherical sampling viewpoints are dynamically generated based on obstacle density. Safe trajectory planning is achieved using a Crested Porcupine Optimizer (CPO). Experiments on the Multi-Drone Multi-Target Tracking (MDMT) dataset demonstrate that the model achieves 84.1% average precision (AP) at 95 Frames Per Second (FPS), striking a favorable balance between speed and accuracy, making it suitable for edge deployment. Field tests with three collaborative UAVs show sustained target coverage in complex environments, outperforming traditional single-UAV approaches. This study provides a systematic solution for robust tracking in challenging low-altitude scenarios. Full article

Cardiovascular aging is a multifactorial and systemic process that contributes significantly to the global burden of cardiovascular disease, particularly in older populations. This review explores the molecular and cellular mechanisms underlying cardiovascular remodeling in age-related conditions such as hypertension, atrial fibrillation, atherosclerosis, and heart failure. Central to this process are chronic low-grade inflammation (inflammaging), oxidative stress, cellular senescence, and maladaptive extracellular matrix remodeling. These hallmarks of aging interact to impair endothelial function, promote fibrosis, and compromise cardiac and vascular integrity. Key molecular pathways—including the renin–angiotensin–aldosterone system, NF-κB, NLRP3 inflammasome, IL-6, and TGF-β signaling—contribute to the transdifferentiation of vascular cells, immune dysregulation, and progressive tissue stiffening. We also highlight the role of the senescence-associated secretory phenotype and mitochondrial dysfunction in perpetuating inflammatory and fibrotic cascades. Emerging molecular therapies offer promising strategies to reverse or halt maladaptive remodeling. These include senescence-targeting agents (senolytics), Nrf2 activators, RNA-based drugs, and ECM-modulating compounds such as MMP inhibitors. Additionally, statins and anti-inflammatory biologics (e.g., IL-1β inhibitors) exhibit pleiotropic effects that extend beyond traditional risk factor control. Understanding the molecular basis of remodeling is essential for guiding future research and improving outcomes in older adults at risk of CVD. Full article

To alleviate the communication burden of wide-area protection and enhance the fault tolerance of multi-source criteria, this paper introduces an improved wide-area backup protection method based on multi-source information fusion. Initially, the variation characteristics of bus sequence voltages after a fault are utilized to screen suspected fault lines, thereby reducing communication traffic. Subsequently, four basic probability assignment functions are constructed using the polarity of zero-sequence current charge, the polarity of phase-difference current charge, and the starting signals of Zone II/III distance protection from the local and adjacent lines. The confidence of each probability function is evaluated using normalized information entropy, while consistency is analyzed via Gaussian similarity, enabling dynamic allocation of fusion weights. Additionally, a conflict adaptation factor is designed to adjust the fusion strategy dynamically, improving fault tolerance in high-conflict scenarios and mitigating the impact of abnormal single criteria on decision results. Finally, the fused fault probability is used to identify the fault line. Simulation results based on the IEEE 39-bus model demonstrate that the proposed algorithm can accurately identify fault lines under different fault types and locations and remains robust under conditions such as information loss and protection maloperation or failure. Full article

The relationship of diabetes mellitus (DM) with cardiovascular mortality and morbidity has been widely established. Diabetic cardiomyopathy (DBCM) has been increasingly recognized as the development of cardiac dysfunction accompanied by heart failure (HF) symptoms in the absence of obvious causes like coronary artery disease (CAD), hypertension (HTN) or valvular diseases. The objective of this review is to critically appraise the role of echocardiography in the diagnosis and prognostic stratification of DBCM. Echocardiography remains the first-line imaging modality due to its availability, repeatability, non-invasive nature and ability to assess structural and functional changes. Classical echocardiographic indices such as left ventricular hypertrophy and systolic and diastolic dysfunction assessment provide valuable information but they lack sensitivity, often remaining normal until advanced stages of DBCM. Recently developed echocardiographic modalities, including strain imaging, myocardial work indices and left atrial strain, may allow for earlier detection of subclinical myocardial dysfunction, having important prognostic implications. However, these advanced modalities require high imaging quality, expertise and standardization, being subject to technical and physio-logical limitations. Stress echocardiography, particularly exercise-based protocols, is an increasingly recognized, valuable tool for unmasking exertional abnormalities in filling pressures, myocardial reserve and pulmonary pressures that are not evident at rest. Until now, stress echocardiography requires validation in large cohorts to assess its prognostic power. This review highlights the importance of timely recognition of DBCM, underscores the advantages and disadvantages of current echocardiographic approaches and outlines future perspectives in multimodality imaging to improve patient outcomes. Full article

Background: Hypertrophic cardiomyopathy (HCM) is a heterogeneous myocardial disease in which conventional prognostic models, primarily focused on sudden cardiac death, often fail to identify patients at risk of clinically relevant events such as heart failure progression or rehospitalization. Cardiopulmonary exercise testing (CPET) quantifies functional capacity, while stress echocardiography (SE) provides mechanistic insights into exercise-induced hemodynamic changes. Their combined application (CPET–SE) may enhance risk stratification in patients with HCM. Methods: In this retrospective study, 388 patients with obstructive and non-obstructive HCM (mean age 48 ± 15 years, 63.1% male) underwent baseline CPET–SE between 2010 and 2022 and were followed for a median of 7.4 years [IQR 4.3–10.2]. Echocardiographic parameters were assessed at rest and peak exercise, and CPET indices included peak oxygen consumption (pVO₂), ventilatory efficiency, and anaerobic threshold. The primary outcome was a composite of heart failure hospitalization or progression to end-stage HCM. Results: Over a median follow-up of 7.4 years, 63 patients (16.2%) experienced an event of the primary outcome. Patients who developed a primary outcome had greater left atrial diameter (45.0 vs. 41.0 mm, p < 0.001) and indexed volume at rest (36.4 vs. 29.0 mL/m², p < 0.001), with further dilation during stress (p = 0.046); increased LV wall thickness (p = 0.001); higher average E/e′ at rest and during stress (p ≤ 0.004); and higher pulmonary artery systolic pressure at rest (p = 0.027) and during stress (p = 0.044). CPET findings included lower pVO₂ (16.0 vs. 19.5 mL/kg/min, p = 0.001), reduced % predicted pVO₂ (p = 0.006), earlier anaerobic threshold (p = 0.032), impaired ventilatory efficiency (p = 0.048), and chronotropic incompetence (p < 0.001) in patients who experienced a primary outcome. Multivariable analysis identified dyslipidemia (OR 2.58), higher E/e′ (OR 1.06), and lower pVO₂ (OR 0.92) as independently associated with the primary outcome. Conclusions: CPET–SE provided a comprehensive evaluation of patients with HCM, associating aerobic capacity to its hemodynamic determinants. Reduced pVO₂ showed the strongest association with adverse outcomes, while exercise-induced diastolic dysfunction and elevated pulmonary pressures identified a high-risk phenotype. Incorporating CPET–SE into longitudinal management of patients with HCM may enable earlier detection of physiological decompensation and guide personalized therapeutic strategies. Full article

When excavating roadways in underground mines, stress redistribution within the surrounding rock mass leads to stress concentration and release. Should the concentrated stresses exceed the rock mass’s tensile or shear strength, rock deformation and failure occur. Thus, a knowledge of stress distribution around the roadway is of great significance for revealing the roadway instability mechanism and design support methods. In this work, the powerful complex variable function theory was used to solve the surrounding rock stress around the triple-arched roadway and the analytical results were verified with the on-site stress state. The results show that the tensile stress occurs on the roadway roof and floor under low lateral stress coefficients, while concentrated compressive stress emerges on the two sidewalls. However, the surrounding stress distribution exhibits an opposite characteristic under high stress levels. Beyond five times the roadway radius, the stress in the surrounding rock is unaffected by the roadway and approaches the in-situ stress. For the +1890 m level trackless transport roadway in Kunyang No. 2 phosphate mine, it is further calculated that the minimum stress concentration factor in the rib area of the roadway within the stress relief zone is 0.34, while the maximum stress concentration factor in the concentrated stress zone of the roof, floor, and sidewalls of the roadway is 5.87. The measured stress values of two monitoring points in the surrounding rock of this roadway are fairly consistent with the analytical values, suggesting the complex variable method for solving excavation-induced stresses are effective and reliable. Full article

Novel coronavirus (SARS-CoV-2) is highly infectious and pathogenic. Novel coronavirus infection can not only cause respiratory diseases but also lead to multiple organ damage through direct or indirect mechanisms, in which the liver is one of the most frequently affected organs. It has been reported that 15–65% of coronavirus disease 2019 (COVID-19) patients experience liver dysfunction, mainly manifested as mild to moderate elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Severe patients may progress to liver failure, develop hepatic encephalopathy, or have poor coagulation function. The mechanisms underlying this type of liver injury are complex. Pathways—including direct viral infection (via ACE2 receptors), immune-mediated responses (e.g., cytokine storm), ischemic/hypoxic liver damage, thrombosis, oxidative stress, neutrophil extracellular trap formation (NETosis), and the gut–liver axis—remain largely speculative and lack robust clinical causal evidence. In contrast, drug-induced liver injury (DILI) has been established as a well-defined causative factor using the Roussel Uclaf Causality Assessment Method (RUCAM). Treatment should simultaneously consider antiviral therapy and liver protection therapy. This article systematically reviewed the mechanism, clinical diagnosis, treatment, and management strategies of COVID-19-related liver injury and discussed the limitations of current research and the future directions, hoping to provide help for the diagnosis and treatment of such patients. Full article

Introduction: Allogeneic hematopoietic cell transplantation (allo-HSCT)-associated thrombotic microangiopathy (TA-TMA) and pre-transplant renal dysfunction are recognized risk factors for mortality after allo-HSCT. Utilizing the data from the Center for International Blood and Marrow Transplant Research (CIBMTR), we investigated the association between onset of TA-TMA and pre-HSCT renal dysfunction on renal failure requiring dialysis (RFD). Methods: We evaluated TA-TMA as a time-dependent covariate in a multivariate Cox regression model for RFD in Allo-HSCT recipients aged ≥ 40 years between 2008 and 2016. Pre-HSCT patients were divided into two groups, estimated GFR (eGFR) < 60 mL/min/1.73 m² group and eGFR ≥ 60 mL/min/1.73 m². Cumulative hazards of RFD in patients with and without onset of TA-TMA were estimated. Results: TA-TMA was significantly associated with increased risk (6.6-fold compared to No TA-TMA) for RFD, the highest of all the significant risk factors. The estimated cumulative hazard for patients with TA-TMA in the two pre-HSCT renal function groups was significantly elevated when compared to similar patients with no TA-TMA (80% vs. 12% for eGFR < 60 mL/min and 50% vs. 5% for eGFR ≥ 60 mL/min group, respectively) at 12 months post-HSCT. Conclusions: Our results demonstrate that the adjusted HR of renal failure requiring dialysis and cumulative hazard was much higher in patients with onset of TA-TMA, especially among patients with pre-existing renal dysfunction, underscoring the importance of early recognition and risk-adapted management. Full article

Penile prosthetic implants (PPIs) provide a definitive surgical solution for individuals requiring restoration of erectile function, most commonly due to medication-refractory erectile dysfunction (ED) or as part of gender-affirming surgical care. During the Anatomical Foundations of Clinical Practice (AFCP) course at Oakland University William Beaumont (OUWB) School of Medicine, a complete three-piece inflatable PPI was identified in a 66-year-old male donor with a medical history of congestive heart failure, hypertension, and diabetes mellitus type 2. The prosthesis included a fluid reservoir positioned in the lower abdominal cavity in the retropubic space, a scrotal pump with a release valve, and paired inflatable cylinders embedded within the penile shaft. This uncommon finding provided first-year medical students with a hands-on opportunity to examine the structure, placement, and function of a modern PPI. In addition to reinforcing foundational knowledge of ED treatment, the case highlighted the expanding clinical indications for penile implants, including their potential role in gender-affirming procedures. Integrating such real-world surgical findings into anatomical education enriches the learning experience of students and highlights the evolving scope of prosthetic urology across diverse patient populations. Full article

Heart failure (HF) marks the culmination of numerous cardiac pathologies, presenting a major medical hurdle in prevention and treatment. In recent years, with the advancements in genomics and metabolomics, research has demonstrated that gut microbiota plays a significant role in the pathogenesis of HF. Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite and primarily sourced from foods abundant in choline, L-carnitine, and betaine. Research has shown that patients with HF exhibit higher levels of TMAO. Accumulating evidence has indicated that TMAO directly or indirectly mediates the occurrence and development of HF through multiple mechanisms. Furthermore, TMAO functions as a crucial prognostic marker in HF. Therefore, TMAO emerges as a potential therapeutic target for HF. This article reviews the generation and metabolic pathways of TMAO, emphasizes its pathophysiological mechanisms in HF, and explores promising therapeutic approaches targeting TMAO, offering novel insights and strategies for HF management. Full article

Infertility remains a major global health concern, with diminished ovarian reserve (DOR), premature ovarian insufficiency (POI), polycystic ovary syndrome (PCOS), and impaired endometrial receptivity representing key contributors to poor assisted reproductive technology (ART) outcomes. Platelet-rich plasma (PRP), an autologous blood-derived concentrate enriched with growth factors and cytokines, has emerged as a promising regenerative therapy with angiogenic, anti-apoptotic, and proliferative properties. In reproductive medicine, intraovarian PRP has been evaluated for its potential to restore ovarian function in women with DOR and POI, improve oocyte competence and embryo euploidy, and promote ovulation in PCOS. Similarly, intrauterine PRP infusion or subendometrial zone injections has shown encouraging results in women with recurrent implantation failure and thin endometrium, enhancing endometrial thickness, receptivity, and implantation potential. Evidence from preclinical animal models and early clinical studies suggests multi-level mechanisms of action, including modulation of endocrine pathways, reduction in oxidative stress, activation of dormant follicles, and improvement of endometrial angiogenesis and receptivity. Despite these promising findings, results remain inconsistent due to heterogeneity in PRP preparation protocols, administration routes, timing, and study designs. Even though robust randomized controlled trials with standardized methodologies are needed to determine the efficacy and long-term reproductive outcomes of PRP in infertility treatment and anovulation in PCOS, PRP represents a novel and potentially transformative adjunct in reproductive endocrinology. Full article

Air pollution is associated with many adverse health outcomes, including kidney diseases. Kidney diseases, especially chronic kidney disease, are a significant public health issue globally. The burden of kidney disease is expected to rise due to population aging and the growing prevalence of diabetes and hypertension. End-stage kidney disease is associated with significant healthcare costs, morbidity, and mortality. Long-term exposure to air pollution was associated with increased risk for chronic kidney disease progression to kidney replacement therapy. Evidence on the effect of short-term exposure to air pollution on renal function is rather limited. Kidney transplant patients are likely to be even more susceptible to detrimental effects of air pollutants. Exposure to air pollution results in a higher risk for delayed graft function, acute rejection, and mortality. In this review we would like to summarize the state of knowledge on the influence of air pollution on outcomes in end-stage kidney failure and kidney transplantation. Full article