Soy isoflavones induces mitophagy to inhibit the progression of osteosarcoma by blocking the AKT/mTOR signaling pathway.

BACKGROUND: Soy isoflavones (SI) is a natural bioactive substance exhibiting beneficial effects on human health. This study aims to elucidate the therapeutic potential of SI in the treatment of osteosarcoma (OS) and to investigate the underlying mechanisms, particularly focusing on mitophagy. METHODS: The effects of SI on the proliferation, apoptosis, migration, and invasion of U2OS cells were analyzed. Mitophagy was assessed through multiple parameters: mitochondrial autophagosomes, mitochondrial membrane potential, autophagy-related proteins, reactive oxygen species (ROS), and oxygen consumption rate (OCR). Protein levels related to apoptosis, autophagy, and the AKT/mTOR pathway were analyzed using western blot. The therapeutic efficacy of SI was further identified using a mouse tumor xenograft model. Cell apoptosis and proliferation in tumor xenografts were detected by TUNEL staining and immunohistochemistry (IHC), respectively. RESULTS: SI dose-dependently suppressed the viability, colony formation, migration, and invasion of U2OS cells, and enhanced the apoptosis. SI also dose-dependently induced mitophagy in OS cells, evidenced by an increase in autophagosomes and ROS levels, a decrease in mitochondrial membrane potential and OCR, and concomitant changes in autophagy-related proteins. Mdivi-1, an inhibitor of mitophagy, reversed the anti-tumor effects of SI on U2OS cells. In addition, SI blocked the AKT/mTOR pathway in U2OS cells. SC-79, an AKT agonist, reversed the effect of SI on inducing mitophagy. Moreover, SI also promoted cell apoptosis and mitophagy in tumor xenografts in vivo. CONCLUSIONS: SI induces mitophagy in OS cells by blocking the AKT/mTOR pathway, contributing to the inhibition of OS.

Right ventricular global strain in patients with hypertrophic cardiomyopathy with and without right ventricular hypertrophy.

PURPOSE: Regardless of whether there are morphological abnormalities of right ventricle in hypertrophic cardiomyopathy (HCM) patients, the exact contribution of right ventricular (RV) global strains remains unresolved. We aimed to study the prognostic value of RV global strains in HCM patients with and without RV hypertrophy (RVH). METHOD: A total of 358 HCM patients who underwent the CMR examination and carried out the follow-up were finally included in this retrospective study. The endpoint was a composite of all-cause mortality, aborted SCD, and heart failure readmission. RV hypertrophy (RVH) was defined as maximal RVWT ≥ 5 mm at end-diastole. RV global strains (RV global longitudinal strain (GLS) and RV global circumferential strain (GCS) were measured in HCM patients by cardiac MRI feature tracking technique. The intraobserver and interobserver reproducibility were evaluated. Receiver-operating characteristic curves and Kaplan-Meier curves, cox proportional hazards regression, Likelihood ratio test and Integrated Discrimination Improvement (IDI) analysis were performed. P-value were corrected for multiple testing when using many covariables by a false discovery rate adjustment. RESULTS: Over a median follow-up of 25 (range 3-54) months, 49 patients reached the composite endpoints. HCM patients were divided into the RVH group and non-RVH groups. In the multivariate cox proportional hazards regression, after adjusting multiple clinical and imaging variables, RV GLS and RV GCS were independently associated with the composite endpoints in the RVH group (HR: 1.123; 95 % CI: 1.048-1.205; P = 0.002) and non-RVH group (HR: 1.174; 95 % CI: 1.031-1.337; P = 0.015), respectively. And The IDI index of models improved when adding RV GLS (IDI = 0.030, p < 0.001) and RV GLS (IDI = 0.056, p = 0.020), respectively. CONCLUSIONS: RV GLS and RV GCS are independent predictors of HCM with RVH and without RVH, respectively. RV GLS in the RVH group and RV GCS in the non-RVH group provide additional values for predicting the risk of adverse events.

Glucagon-Like Peptide-1 Inhibits the Progression of Abdominal Aortic Aneurysm in Mice: The Earlier, the Better.

OBJECTIVES: Glucagon-like peptide-1 (GLP-1) has a cardiovascular protective effect by preventing abdominal aortic aneurysm (AAA) formation. However, it is unclear at what point the agent should be administered to achieve the optimal effect. In this study, we aimed to determine whether administering the GLP-1 receptor agonist liraglutide during the earlier stages would more efficiently inhibit AAA progression in mice. METHODS: Depending on the group, mice were given a daily dose of 300 µg/kg liraglutide for 28 days at 7, 14, and 28 days after aneurysm induction. The morphology of the abdominal aorta was monitored using 7.0 T magnetic resonance imaging (MRI) during the administration of liraglutide. After 28 days of administration, the AAA dilatation ratio was calculated, and histopathological examination was performed. Oxidative stress levels were evaluated by the expression of malondialdehyde (MDA) and matrix metalloproteinases (MMPs). The inflammatory response was also evaluated. RESULTS: Liraglutide treatment led to a decrease in AAA formation, including a reduction in abdominal aorta expansion, elastin degradation in the elastic laminae, and vascular inflammation caused by leukocyte infiltration. The expression of MDA and the activity of MMPs (MMP-2, MMP-9) also decreased. Notably, administering liraglutide during the early stages resulted in a significant reduction in the dilatation rate of the aortic wall, as well as in MDA expression, leukocyte infiltration, and MMP activity in the vascular wall. CONCLUSIONS: The GLP-1 receptor agonist liraglutide was found to inhibit AAA progression in mice by exerting anti-inflammatory and antioxidant effects, particularly during the early stages of AAA formation. Therefore, liraglutide may represent a potential pharmacological target for the treatment of AAA.

A radiomics model based on aortic computed tomography angiography: the impact on predicting the prognosis of patients with aortic intramural hematoma (IMH).

Background: The prognosis of aortic intramural hematoma (IMH) is unpredictable, but computed tomography angiography (CTA) plays an important role of high diagnostic performance in the initial diagnosis and during follow-up of patients. In this study, we investigated the value of a radiomics model based on aortic CTA for predicting the prognosis of patients with medically treated IMH. Method: A total of 120 patients with IMH were enrolled in this study. The follow-up duration ranged from 32 to 1,346 days (median 232 days). Progression of these patients was classified as follows: destabilization, which refers to deterioration in the aortic condition, including significant increases in the thickness of the IMH, the progression of IMH to a penetrating aortic ulcer (PAU), aortic dissection (AD), or rupture; or stabilization, which refers to an unchanged appearance or a decrease in the size or disappearance of the IMH. The patients were divided into a training cohort (n=84) and a validation cohort (n=36). Six different machine learning classifiers were applied: random forest (RF), K-nearest neighbor (KNN), Gaussian Naive Bayes, decision tree, logistic regression, and support vector machine (SVM). The clinical-radiomics combined nomogram model was established by multivariate logistic regression. The area under the receiver operating characteristic (ROC) curve (AUC) was implemented to evaluate the discrimination performance of the models. The calibration curves and Hosmer-Lemeshow test were used for evaluating model calibration. DeLong's test was performed to compare the AUC performance of models. Results: Among all of the patients, 60 patients showed destabilization and 60 patients remained stable. A total of 12 radiomic features were retained after application of the least absolute shrinkage and selection operator (LASSO). These features were used for the machine learning model construction. The SVM-radial basis function (SVM-RBF) model obtained the best performance with an AUC of 0.765 (95% CI, 0.593-0.906). In the validation cohort, the combined clinical-radiomics model [AUC =0.787; 95% confidence interval (CI), 0.619-0.923] showed a significantly higher performance than did the clinical model (AUC =0.596; 95% CI, 0.413-0.796; P=0.021) and had a similar performance to the radiomics model (AUC =0.765; 95% CI, 0.589-0.906; P=0.672). Conclusions: A quantitative nomogram based on radiomic features of CTA images can be used to predict disease progression in patients with IMH and may help improve clinical decision-making.

Emergency Endovascular Management of Inadvertent False Lumen Stent Graft Implantation After Frozen Elephant Trunk Procedure: A Case Report.

CLINICAL IMPACT: This technology is a good supplement to the clinical practice, providing a new solution to the problem of stent placement in the prosthetic cavity, avoiding the patient to have another surgical operation, which is good for both medicine and patients.

[Characterization of greenhouse gas emissions and stable isotopic composition of ammonia during industrial composting process]. / å·¥åŽ‚åŒ–å †è‚¥æ¸©å®¤æ°”ä½“æŽ’æ”¾å’Œæ°¨æ°”åŒä½ç´ ç‰¹å¾.

Carbon dioxide (CO2), nitrous oxide (N2O), methane (CH4) and ammonia (NH3) emitted during the composting of livestock and poultry waste are important gaseous atmospheric pollutants. However, most previous studies on compost-related anthropogenic emissions of these gases were based on small reactor composting. Our understanding of their in situ emissions during industrial composting remains extremely limited. In order to explore the influence of gas produced by industrial composting on regional environment, we monitored CO2, CH4, N2O and NH3 emissions during industrial composting for 19 days and characterized the isotopic composition of emitted NH3. On average, the emission rates of CO2, CH4, N2O, and NH3 during the composting cycle were 86.8 g CO2-C·d-1·m-2, 9.8 g CH4-C·d-1·m-2, 3.7 mg N2O-N·d-1·m-2 and 736.6 mg NH3-N·d-1·m-2, respectively. The contribution of CH4 to daily global warming potential (GWP) was the highest (65%), followed by CO2, NH3(indirect), and N2O. Moreover, ammonia emitted from industrial compost had a mean δ15N value of -11.6‰±1.2‰ (range: -21.8‰--7.2‰). Overall, this study provided useful information for understanding greenhouse gas emission dynamics and characterizing atmospheric NH3 sources during composting process in livestock and poultry breeding areas.

Quantification of Myocardial Deformation in Patients with Takayasu Arteritis by Cardiovascular Magnetic Resonance Feature Tracking Imaging.

BACKGROUND: Cardiac involvement is one of the main causes of morbidity and mortality in patients with Takayasu arteritis (TA). Early detection and intervention of cardiac damage may be helpful to reduce the mortality of TA. Magnetic resonance (MR) imaging (MRI)-derived feature tracking (FT) is an effective quantitative method to assess myocardial deformation which may reflect early changes of cardiac function. PURPOSE: To explore the utility of MR-FT as a method to detect cardiac damage in TA patients. STUDY TYPE: Retrospective. POPULATION: Fifty-seven TA patients who had undergone clinically indicated MRI and 57 healthy controls. FIELD STRENGTH/SEQUENCES: Balanced steady-state free precession rest cine and 2D phase-sensitive inversion recovery breath-hold segmented gradient echo late gadolinium enhancement (LGE) sequences at 3.0 T. ASSESSMENT: Based on LGE images, TA patients were divided into two subgroups, LGE (+) subgroup (N = 12) and LGE (-) subgroup (N = 45). In addition, patients were further subdivided into impaired (N = 26) and preserved left ventricle ejection fraction (LVEF) subgroups (N = 31). FT-derived deformation indices, including left ventricular (LV) global longitudinal strain (GLS), were measured by commercial software. STATISTICAL TESTS: Mann-Whitney U-test, Kruskal-Wallis test followed by Dunn-Bonferroni post hoc method, and receiver operating characteristic curve analysis were conducted. A P-value of <0.05 was considered statistically significant. RESULTS: GLS was significantly worse in TA than in controls (median [interquartile range, IQR]: TA -10.0 [-7.5 to 12.4] vs. controls -12.7 [-11.8 to 14.7]). Moreover, TA patients with LGE (+) had significantly poorer GLS than those with LGE (-) (median [IQR]: LGE (+) -6.8 [-4.0 to 8.1] vs. LGE (-) -10.7 [-8.5 to 12.9]). The reduced LVEF subgroup had significantly greater cardiac dysfunction as measured by MR-FT than the preserved LVEF subgroup (GLS median [IQR]: reduced LVEF -7.9 [-6.2 to 11.4] vs. preserved LVEF -10.8 [-8.6 to 13.5]). DATA CONCLUSION: Myocardial deformation impairment was found in the majority of TA patients. MR-FT imaging may be helpful in the early diagnosis and management of TA patients. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 5.

[N2O and N2 emission characteristics from maize and greenhouse vegetable soils in Northern China]. / æˆ‘å›½åŒ—æ–¹å‡ ç§çŽ‰ç±³å’Œè®¾æ–½èœåœ°åœŸå£¤çš„N2O和N2排放特征.

To explore N2O and N2 emissions from upland soils after nitrogen fertilizer application, a 60-day aerobic incubation experiment (25 ℃,80% water-filled pore space) using the 15N tracing method was conducted to quantify the N transformation, N2O and N2 emissions from maize soils from four sites (Harbin, Shenyang, Luancheng and Shouguang) and vegetable soils from two sites (Shen-yang and Shouguang), with urea being applied at 167 mg N·kg-1 to simulate the field application rate of 200 kg N·hm-2. The results showed that for the four sites with maize soils, the cumulative emission of N2O was in the order of Shouguang (20 mg N·kg-1) > Luancheng (14 mg N·kg-1) > Shenyang (5 mg N·kg-1) > Harbin (0.5 mg N·kg-1) and the cumulative N2 emission was in the order of Luancheng (176 mg N·kg-1) > Shenyang (106 mg N·kg-1) > Shouguang (75 mg N·kg-1) > Harbin (12 mg N·kg-1). For vegetable soils, the cumulative N2O emission of Shouguang (21 mg N·kg-1) was 10 times of that of Shenyang (2 mg N·kg-1), but without differences in cumulative N2 emissions (28 and 24 mg N·kg-1, respectively). The N2O/(N2O+N2) of the six soils ranged from 5% to 40%. The N2O/(N2O+N2) of the two soils from Shouguang (30%-40%) was significantly higher than other four soils (1%-10%). Soil bulk N pool contributes to 56% of total N2O emission and 61% of total N2 emission, which was higher than the contribution of fertilizer. The cumulative N2O emission was positively correlated with soil background pH, which indicated that soil background pH might be an important factor regulating N2O and N2 emission from upland soils. In the alkaline soil regions of North China Plain (such as Luancheng and Shouguang), mea-sures to reduce soil pH might have great impact on reducing N gaseous emission.