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Chronic kidney disease (CKD) is associated with a significantly elevated mortality rate, primarily due to cardiovascular disease (CVD), highlighting a complex bidirectional relationship between the two conditions. Life-threatening cardiovascular events occur despite control of the traditional risk factors, emphasizing the underlying role of non-traditional risk factors. CKD, causing mineral imbalance and the accumulation of uremic toxins due to a compromised ability to excrete waste products, imposes extra pressure on the cardiovascular system. The retention of mineral and uremic toxins, in turn, aggravates the progression of CKD. This review aims to elucidate the pathophysiological connections between CKD and CVD, with a particular focus on the metabolic regulatory mechanisms influenced by minerals such as calcium and phosphate, as well as uremic toxins. We review how these factors contributed to accelerated multi-organ damage through mechanisms such as inflammation, endothelial dysfunction, oxidative stress, and vascular calcification. In addition, we discuss the therapeutic strategies for specific uremic toxins and proposed directions for future investigations. This review provides insights into the complex interplay between metabolic dysregulation and cardiovascular outcomes in CKD patients, promoting the development of innovative therapeutic interventions, ultimately improving the prognosis and quality of life for patients affected by these interconnected conditions.

Lipid metabolism involves multiple biological processes. As one of the most important lipid metabolic pathways, fatty acid oxidation (FAO) and its key rate-limiting enzyme, the carnitine palmitoyltransferase (CPT) system, regulate host immune responses and thus are of great clinical significance. The effect of the CPT system on different tissues or organs is complex: the deficiency or over-activation of CPT disrupts the immune homeostasis by causing energy metabolism disorder and inflammatory oxidative damage and therefore contributes to the development of various acute and chronic inflammatory disorders and cancer. Accordingly, agonists or antagonists targeting the CPT system may become novel approaches for the treatment of diseases. In this review, we first briefly describe the structure, distribution, and physiological action of the CPT system. We then summarize the pathophysiological role of the CPT system in chronic obstructive pulmonary disease, bronchial asthma, acute lung injury, chronic granulomatous disease, nonalcoholic fatty liver disease, hepatic ischemia–reperfusion injury, kidney fibrosis, acute kidney injury, cardiovascular disorders, and cancer. We are also concerned with the current knowledge in either preclinical or clinical studies of various CPT activators/inhibitors for the management of diseases. These compounds range from traditional Chinese medicines to novel nanodevices. Although great efforts have been made in studying the different kinds of CPT agonists/antagonists, only a few pharmaceuticals have been applied for clinical uses. Nevertheless, research on CPT activation or inhibition highlights the pharmacological modulation of CPT-dependent FAO, especially on different CPT isoforms, as a promising anti-inflammatory/antitumor therapeutic strategy for numerous disorders.

Aims/Introduction Regulatory T cells (Tregs) have protected against many cardiovascular diseases. This study was intended to explore the effect of Tregs on diabetic cardiomyopathy (DCM) using a db/db mouse model. Materials and methods Eight‐week‐old male db/db mice were randomly divided into four groups: the control group, administered 200 μL phosphate‐buffered saline; the small‐dose Treg group, administered 105 Tregs; the large‐dose Treg group, administered 106 Tregs; and the PC group, administered 100 μg anti‐CD25 specific antibody (PC61) and 106 Tregs. After 12 weeks, mice were euthanized. Transthoracic echocardiography was carried out at the beginning and end of the experiment. Relevant basic experiments to evaluate the effects of Tregs on DCM were carried out. Results Echocardiography showed that the impaired diastolic and systolic functions were significantly improved in mice administered large‐dose Tregs. Large‐dose Tregs significantly ameliorated myocardial hypertrophy and fibrosis, and decreased hypertrophic gene expression and collagen deposition. The protective effects of Tregs on diabetic hearts were associated with decreased oxidative stress, inflammatory response and apoptosis. In addition, Tregs promoted the activation of the phosphatidylinositol 3‐kinase–protein kinase B signaling pathway, whereas they inhibited extracellular signal‐regulated kinase 1/2 and Jun N‐terminal kinase phosphorylation, which might be responsible for the cardioprotective role of Tregs against DCM. Conclusions Tregs ameliorated myocardial hypertrophy and fibrosis, improved cardiac dysfunction, and protected against DCM progression in db/db mice. The mechanisms involved a decrease of inflammatory response, oxidative stress and apoptosis, which might be mediated by phosphatidylinositol 3‐kinase–protein kinase B and mitogen‐activated protein kinase pathways. Hence, Tregs might serve as a promising therapeutic approach for DCM treatment. Regulatory T cells ameliorated myocardial hypertrophy and fibrosis, improved cardiac dysfunction, and protected against diabetic cardiomyopathy progression in db/db mice. The mechanisms involved a decrease of inflammatory response, oxidative stress and apoptosis, which might be mediated by the phosphoinositide 3‐kinases–protein kinase B and mitogen‐activated protein kinase pathways.

Objective Using qualitative and quantitative magnetic resonance imaging (MRI) features, this study aimed to distinguish between isocitrate dehydrogenase (IDH)-mutant astrocytomas (IDH-mA) and IDH-wildtype glioblastomas (IDH-wG) based on the fifth edition of the World Health Organization’s (WHO’s) classification of central nervous system (CNS) tumors (WHO CNS5), published in 2021. Methods We enrolled 87 IDH-mA and 102 IDH-wG patients with pathologically confirmed disease according to the WHO CNS5 standard. Pretreatment brain MRI images and genetic information were obtained for each patient. Qualitative imaging features were assessed, including the side of lesion center, multifocality/multicentricity, hemorrhage, pial invasion, ependymal invasion, cortical involvement, midline location invasion, and enhancement mode. The quantitative imaging features assessed included tumor volume-related metrics and the relative apparent diffusion coefficient (rADC)-related metrics based on tumor segmentation. Contrast-enhanced and non-enhanced areas of the tumors were analyzed separately. univariable analysis and logistic regression were used to select the candidate predictors. The discrimination performance of the logistic regression model was evaluated using the area under the receiver operating characteristic curve (AUC). Internal validation was performed using the bootstrap approach. Results In terms of the qualitative features, IDH-mA exhibited less multifocality/ multicentricity ( p  = 0.032), more hemorrhage ( p  = 0.009), and more cortical involvement ( p  = 0.009) than IDH-wG. Regarding the quantitative imaging features, IDH-mA demonstrated higher values in V all ( p  = 0.001), V ne ( p  < 0.001), rmaxADC ce ( p  < 0.001), rminADC ne ( p  = 0.015), rmaxADC ne ( p  = 0.004), and rmeanADC all ( p  = 0.001) than IDH-wG. In the multivariable analysis of all patients, multifocality/multicentricity (odds ratio [OR] = 2.87, p  = 0.033), V ne (OR = 1.02, p  = 0.049), and rmaxADC ce (OR = 2.82, p  < 0.001) were independent predictive factors for distinguishing IDH-mA from IDH-wG. A combination of multifocality/multicentricity, V ne , and rmaxADC ce (model) had a superior performance in distinguishing IDH-mA from IDH-wG, with an AUC, accuracy, sensitivity, and specificity of 0.849 (95% confidence interval [CI], 0.791–0.908), 76.5%, 66.3%, and 92.3%, respectively. Conclusions We found that the combination of multifocality/multicentricity, V ne , and rmaxADC ce , can help distinguish between IDH-mA and IDH-wG effectively.

Previous studies suggested a beneficial effect of natriuretic peptides in animal models of cardiovascular disease, but the role of natriuretic peptide receptor C (NPRC) in the pathogenesis of atherosclerosis (AS) remains unknown. This study was designed to test the hypothesis that NPRC may promote AS lesion formation and instability by enhancing oxidative stress, inflammation, and apoptosis via protein kinase A (PKA) signaling. ApoE −/− mice were fed chow or Western diet for 12 weeks and NPRC expression was significantly increased in the aortic tissues of Western diet-fed mice. Systemic NPRC knockout mice were crossed with ApoE −/− mice to generate ApoE −/− NPRC −/− mice, and NPRC deletion resulted in a significant decrease in the size and instability of aortic atherosclerotic lesions in ApoE −/− NPRC −/− versus ApoE −/− mice. In addition, endothelial cell-specific NPRC knockout attenuated atherosclerotic lesions in mice. In contrast, endothelial cell overexpression of NPRC aggravated the size and instability of atherosclerotic aortic lesions in mice. Experiments in vitro showed that NPRC knockdown in human aortic endothelial cells (HAECs) inhibited ROS production, pro-inflammatory cytokine expression and endothelial cell apoptosis, and increased eNOS expression. Furthermore, NPRC knockdown in HAECs suppressed macrophage migration, cytokine expression, and phagocytosis via its effects on endothelial cells. On the contrary, NPRC overexpression in endothelial cells resulted in opposite effects. Mechanistically, the anti-inflammation and anti-atherosclerosis effects of NPRC deletion involved activation of cAMP/PKA pathway, leading to downstream upregulated AKT1 pathway and downregulated NF-κB pathway. In conclusion, NPRC deletion reduced the size and instability of atherosclerotic lesions in ApoE −/− mice via attenuating inflammation and endothelial cell apoptosis and increasing eNOS expression by modulating cAMP/PKA-AKT1 and NF-κB pathways. Thus, targeting NPRC may provide a promising approach to the prevention and treatment of atherosclerosis.

A robust Folin–Ciocalteu method, coupled with an optimized ultrasonic-assisted extraction, was established for accurate quantification of total polyphenols in high-oil grape seed matrices, where lipid interference and low extraction efficiency have been persistent challenges. Samples were first defatted with n-hexane to eliminate lipid interference. Key colorimetric parameters—Folin–Ciocalteu reagent volume, Na2CO3 concentration, reaction temperature, and time—were systematically optimized and validated for linearity, precision, and recovery. Subsequently, using defatted grape seed powder as the raw material, a four-factor, three-level Box–Behnken design combined with response surface methodology was employed to optimize the four extraction parameters: solid-to-liquid ratio, ethanol concentration, extraction temperature, and extraction time. The optimal conditions were 0.5 mL of Folin–Ciocalteu reagent, 20% Na2CO3, and reaction at 30 °C for 2.0 h, yielding a linear calibration curve (R2 = 0.9991) with satisfactory methodological validation. Optimal extraction (52% ethanol, 1:50 w/v, 68 °C, 21 min) achieved a total polyphenol content of 2.93 × 104 mg·kg−1, closely matching the predicted value (relative error = 0.34%). Analysis of seven grape seed varieties from the Hebei Province revealed significant content variation (p < 0.05), ranging from 3.24 to 7.47 × 104 mg·kg−1, with Rose grape seeds exhibiting the highest level. The developed method effectively overcame matrix interference from high oil content, offering a reliable, efficient tool for screening high-polyphenol grape seed varieties and supporting the development of value-added functional products.

The pathogenesis of doxorubicin-induced cardiomyopathy remains unclear. This study was carried out to test our hypothesis that ADAM17 aggravates cardiomyocyte apoptosis induced by doxorubicin and inhibition of ADAM17 may ameliorate doxorubicin-induced cardiomyopathy. C57BL/6J mice were intraperitoneally injected with a cumulative dose of doxorubicin to induce cardiomyopathy. Cardiomyocyte-specific ADAM17-knockout (A17 α-MHCKO ) and ADAM17-overexpressing (AAV9-oeA17) mice were generated. In addition, RNA sequencing of the heart tissues in different mouse groups and in vitro experiments in neonatal rat cardiomyocytes (NRCMs) receiving different treatment were performed. Mouse tumor models were constructed in A17 fl/fl and A17 α-MHCKO mice. In addition, cardiomyocyte-specific TRAF3-knockdown and TRAF3-overexpressing mice were generated. ADAM17 expression and activity were markedly upregulated in doxorubicin-treated mouse hearts and NRCMs. A17 α-MHCKO mice showed less cardiomyocyte apoptosis induced by doxorubicin than A17 fl/fl mice, and cardiomyocyte ADAM17 deficiency did not affect the anti-tumor effect of doxorubicin. In contrast, AAV9-oeA17 mice exhibited markedly aggravated cardiomyocyte apoptosis relative to AAV9-oeNC mice after doxorubicin treatment. Mechanistically, doxorubicin enhanced the expression of transcription factor C/EBPβ, leading to increased expression and activity of ADAM17 in cardiomyocyte, which enhanced TNF-α shedding and upregulated the expression of TRAF3. Increased TRAF3 promoted TAK1 autophosphorylation, resulting in activated MAPKs pathway and cardiomyocyte apoptosis. ADAM17 acted as a positive regulator of cardiomyocyte apoptosis and cardiac remodeling and dysfunction induced by doxorubicin by upregulating TRAF3/TAK1/MAPKs signaling. Thus, targeting ADAM17/TRAF3/TAK1/MAPKs signaling holds a promising potential for treating doxorubicin-induced cardiotoxicity.

Aiming at the problems of low detection accuracy and large computing resource consumption of existing Unmanned Aerial Vehicle (UAV) detection algorithms for anti-UAV, this paper proposes a lightweight UAV swarm detection method based on You Only Look Once Version X (YOLOX). This method uses depthwise separable convolution to simplify and optimize the network, and greatly simplifies the total parameters, while the accuracy is only partially reduced. Meanwhile, a Squeeze-and-Extraction (SE) module is introduced into the backbone to improve the model′s ability to extract features; the introduction of a Convolutional Block Attention Module (CBAM) in the feature fusion network makes the network pay more attention to important features and suppress unnecessary features. Furthermore, Distance-IoU (DIoU) is used to replace Intersection over Union (IoU) to calculate the regression loss for model optimization, and data augmentation technology is used to expand the dataset to achieve a better detection effect. The experimental results show that the mean Average Precision (mAP) of the proposed method reaches 82.32%, approximately 2% higher than the baseline model, while the number of parameters is only about 1/10th of that of YOLOX-S, with the size of 3.85 MB. The proposed approach is, thus, a lightweight model with high detection accuracy and suitable for various edge computing devices.

In recent years, the increasing number of unmanned aerial vehicles (UAVs) in the low-altitude airspace have not only brought convenience to people’s work and life, but also great threats and challenges. In the process of UAV detection and tracking, there are common problems such as target deformation, target occlusion, and targets being submerged by complex background clutter. This paper proposes an anti-occlusion UAV tracking algorithm for low-altitude complex backgrounds by integrating an attention mechanism that mainly solves the problems of complex backgrounds and occlusion when tracking UAVs. First, extracted features are enhanced by using the SeNet attention mechanism. Second, the occlusion-sensing module is used to judge whether the target is occluded. If the target is not occluded, tracking continues. Otherwise, the LSTM trajectory prediction network is used to predict the UAV position of subsequent frames by using the UAV flight trajectory before occlusion. This study was verified on the OTB-100, GOT-10k and integrated UAV datasets. The accuracy and success rate of integrated UAV datasets were 79% and 50.5% respectively, which were 10.6% and 4.9% higher than those of the SiamCAM algorithm. Experimental results show that the algorithm could robustly track a small UAV in a low-altitude complex background.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remain devastating clinical entities characterized by uncontrolled pulmonary inflammation driven by dysregulated macrophage activation, with limited therapeutic options and high mortality. Emerging evidence implicates neuroimmune crosstalk as a pivotal regulator in inflammatory disorders, yet the role of dopaminergic signaling in orchestrating macrophage function during ALI remains ill-defined. Herein, we systematically characterized the dynamic perturbations of pulmonary dopaminergic signaling during ALI/ARDS progression and delineated the anti-inflammatory and cytoprotective properties of dopamine (DA) D1-like receptor (D1R) signaling in ALI mouse model and targeted macrophages. Mechanistically, DA-D1R activation mitigated macrophage hyperactivation by reversing lipopolysaccharide-induced mitochondrial dysfunction, thereby curbing excessive M1 polarization and maintaining cellular homeostasis. Transcriptomic profiling identified junctional adhesion molecule-like protein (JAML) as a critical downstream effector of the D1R agonist SKF38393 (SKF) in macrophages. SKF downregulated JAML expression and its interaction with interleukin (IL)-10, thus enhancing IL-10 bioavailability to sustain mitochondrial integrity and limit oxidative damage. Notably, the anti-inflammatory capacity of DA bioactivity system was validated in macrophages from ARDS patients and healthy controls, underscoring its translational potential. Collectively, our findings unravel a previously unrecognized DA-D1R-JAML/IL-10-mitochondria axis that governs macrophage-mediated ALI, positioning dopaminergic signaling as a promising therapeutic target for ARDS and other inflammatory disorders involving neuroimmune dysfunction. Graphical Abstract ToC text: The study design and the mechanism by which DA signaling acting on D1R regulates M1 macrophages (M1-Mφ) via JAML/IL-10-mediated mitochondrial regulation in ALI/ARDS.