Dapagliflozin modulates the faecal microbiota after myocardial infarction in non-diabetic mice.

The gut microbiota seems to be a major modulator of cardiovascular diseases, such as myocardial infarction. Dapagliflozin, a sodium glucose cotransporter 2 inhibitor (SGLT2i), is an antidiabetic agent that was recently utilized in patients with cardiovascular diseases. This study aims to investigate the effects of dapagliflozin on the faecal microbiota of postinfarction non-diabetic mice. A total of 19 male mice were randomly divided into three groups, where two groups were enduced with myocardial infarction (MI) by left anterior descending ligation. One day after the surgery, each group was administered normal saline (15 mL/kg/day, 0.9%) or dapagliflozin (1.5 mg/kg/day) for 4 weeks. Echocardiography was obtained on day 28 post MI. Masson's trichrome staining was used to determine the degree of fibrosis. Faecal samples were collected to assess the microbiome by 16S ribosomal RNA gene sequencing. We found that dapagliflozin significantly improved cardiac function in the non-diabetic myocardial infarction mice model after the 28-day treatment, especially in ejection fraction and fractional shortening (p < 0.01). Enterotypes were composed of Muribaculaceae and Lactobacillaceae after dapagliflozin treatment, while Muribaculaceae and Erysipelotrichaceae were the main enterotypes post-MI. Dapagliflozin increased the abundance of beneficial bacteria like Lactobacillaceae, while decreasing the abundance of beneficial bacteria like Bifidobacteriaceae. It was interesting to discover that Proteobacteria (especially Desulfovibrionaceae) were enriched after the dapagliflozin treatment for myocardial infarction. Dapagliflozin increased the abundance of the main beneficial bacteria. In post-myocardial infarction treatments, using dapagliflozin could positively contribute to the improvement of cardiac function and alter the structure of faecal microbiota.

Relationship between serum uric acid and sarcopenia in geriatric heart failure patients with preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) presents a serious risk to human health. The increased prevalence of sarcopenia in the HFpEF population has a negative impact on patient prognosis. Uric acid (UA) is the byproduct of purine metabolism and is harmful to the cardiovascular system. This study aims to establish the potential relationship between sarcopenia and serum UA in HFpEF patients. METHODS: Data were obtained from 180 individuals (aged ≥60 years) with HFpEF admitted to the Geriatric Department of Jiangsu Province Hospital between January 2021 and December 2022. The UA values were grouped into 4 quartiles (Q1-Q4). Logistic generalized linear models and restricted cubic spline (RCS) regression were used to analyze the relationship between sarcopenia and UA. Subgroups based on gender were utilised for further analysis. RESULTS: After adjusting for covariates, odds ratios (ORs) and 95 % confidence intervals (CIs) for sarcopenia prevalence in the 2nd, 3rd, and 4th quartiles were 2.56 (0.57-12.65), 4.94 (1.10-24.49), and 6.95 (1.30-44.25), respectively, unlike the 1st quartile (P for trend = 0.022). The RCS plot demonstrated a positive linear relationship between serum UA levels and sarcopenia (P for non-linearity = 0.190). A sex-based subgroup analysis revealed a statistically significant relationship between UA and sarcopenia in males (P < 0.05). CONCLUSIONS: In summary, the prevalence of sarcopenia is positively related to serum UA levels among the elderly diagnosed with HFpEF. Due to the cross-sectional nature of the study design, additional investigations are necessary to validate our findings and identify the optimal range for UA reduction.

Association of urinary thallium with hypertension in children and adolescents aged 8-17 years: NHANES 2005-2018.

Hypertension is a key risk factor for cardiovascular disease (CVD). Thallium is a highly toxic metal that exists in all aspects of our lives and can cause damage to human health. The aim of this study was to identify the potential correlation between urinary thallium (U-Tl) and hypertension in American youth aged 8-17 years. The National Health and Nutritional Examination Survey (NHANES) database was mined for cross-sectional information on 2295 American children and adolescents aged 8-17 years. Inductively coupled plasma mass spectrometry (ICP-MS) was utilized to measure U-Tl levels, and the results were categorized into four quartiles (Q1-Q4). Logistic generalized linear models and unweighted restricted cubic spline (RCS) regression were used to investigate the relationship between U-Tl and hypertension. After adjusting for covariates, the odds ratios (ORs) at 95% confidence intervals (CIs) for hypertension prevalence in the 2nd, 3rd, and 4th quartiles were 0.43 (0.22-0.81), 0.54 (0.29-0.99), and 0.43 (0.22-0.81), when compared to the lowest quartile (P for trend = 0.024). RCS plot showed a negative linear correlation between log2-transformed U-Tl levels and hypertension (P for non-linearity = 0.869). Subgroup analysis based on sex indicated a statistically significant link between U-Tl and hypertension in male (P < 0.05). There is a negative linear relationship between U-Tl and hypertension in American children and adolescents aged 8-17 years with low thallium exposure. Due to the nature of cross-sectional studies, further studies are necessary to validate our conclusions and elucidate possible mechanisms.

Association of Blood Heavy Metal Exposure with Atherosclerotic Cardiovascular Disease (ASCVD) Among White Adults: Evidence from NHANES 1999-2018.

Cardiovascular diseases (CVD) are main public health concerns highly prevalent in industrialized societies where human health is threatened by a series of environmental pollutants, particularly heavy metal contaminants. We aimed to find out if blood heavy metals are associated with the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in a nationally representative sample of US adults. We analyzed the cross-sectional data on blood heavy metals of 3268 non-Hispanic white participants aged 40-79 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. We introduced a risk estimation algorithm, namely the 2013 Pooled Cohort Equations (PCE), to assess the risk for ASCVD over a 10-year period. The 10-year risk for ASCVD was categorized as either reduced risk (< 7.5% risk) or elevated risk (≥ 7.5% risk). Blood lead, cadmium, and mercury were distributed into four quartiles. We used weighted multivariate logistic regression models and restricted cubic spline (RCS) regression to detect the association of blood heavy metal exposure with 10-year ASCVD risk. Following the adjustment of covariates, the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for elevated 10-year ASCVD risk for participants from the highest quartiles were 4.50 (2.88-7.02), 2.59 (1.68-4.00), and 1.06 (0.66-1.71) for blood cadmium, lead, and mercury compared to the lowest quartiles, respectively. The RCS plot demonstrated that blood cadmium was linearly and positively associated with 10-year ASCVD risk (P for nonlinearity = 0.112). According to our findings, non-Hispanic whites aged 40-79 years had a greater 10-year ASCVD risk as their blood lead and cadmium levels increased. Consequently, when establishing approaches for ASCVD prevention, blood heavy metals should be considered.

Klotho improves cardiac fibrosis, inflammatory cytokines, ferroptosis, and oxidative stress in mice with myocardial infarction.

The anti-aging protein Klotho has been associated with cardiovascular health protection. Nevertheless, the protective mechanism remains unknown. The present study is aimed at exploring the effect of Klotho on cardiac remodeling and its potential mechanism in mice with myocardial infarction (MI). We used left anterior coronary artery descending ligation to develop an MI model for in vivo analyses. In contrast, H9C2 cells and cardiac fibroblasts were used to establish the oxygen-glucose deprivation (OGD) model in in vitro analyses. In vivo and in vitro models were treated with Klotho. Compound C, an AMPK signaling inhibitor, was used to determine whether Klotho's effects are mediated through the AMPK/mTOR signaling pathway. Echocardiography, Masson trichrome staining, immunofluorescence, immunohistochemistry, real-time polymerase chain reaction (RT-PCR), and western blot were used to detect the related indicators. The findings of the in vivo model indicate that Klotho treatment improved the mice's cardiac function, reduced cardiac fibrosis, and attenuated myocardial inflammatory factors, ferroptosis, and oxidative stress. The results of the in vitro model were in line with the findings of in vivo modeling. An AMPK inhibitor, Compound C, reversed all these effects. In conclusion, Klotho potentially improves cardiac remodeling in MI mice by regulating AMPK/mTOR signaling, demonstrating Klotho as an effective MI therapeutic agent.

Towards efficient network compression via Few-Shot Slimming.

While previous network compression methods achieve great success, most of them rely on the abundant training data which is, unfortunately, often unavailable in practice due to some reasons, e.g., privacy issues, storage constraints, and transmission limitations. A promising way to solve this problem is to perform compression with a few unlabeled data. Proceeding along this way, we propose a novel few-shot network compression framework named Few-Shot Slimming (FSS). FSS follows the student/teacher paradigm, and contains two steps: (1) construct the student by inheriting principal feature maps from the teacher; (2) refine the student feature representation by knowledge distillation with an enhanced mixing data augmentation method called GridMix. Specifically, in the first step, we employ normalized cross correlation to perform the principal feature analysis, and then theoretically construct a new indicator to select the most informative feature maps from the teacher for the student. The indicator is based on the variances of feature maps which can efficiently quantitate the information richness of the input feature maps in a feature-agnostic manner. In the second step, we perform the knowledge distillation for the initialized student in first step with a novel grid-based mixing data augmentation technique which greatly extends the limited sample dataset. In this way, the student is able to refine its feature representation and achieves a better result. Extensive experiments on multiple benchmarks demonstrate the state-of-the-art performance of FSS. For example, by using 0.2% label-free data of full training set, FSS yields a 60% FLOPs reduction for DenseNet-40 on CIFAR-10 with only a loss of 0.8% in top-1 accuracy, achieving a result on par with that obtained by the conventional full-data methods.

Dapagliflozin Improves Cardiac Function, Remodeling, Myocardial Apoptosis, and Inflammatory Cytokines in Mice with Myocardial Infarction.

Dapagliflozin (DAPA) exerts cardioprotective effects in non-diabetic patients. Nonetheless, the protective mechanism remains unknown. This study aims to evaluate the performance of DAPA on cardiac function and remodeling as well as its potential mechanism in mice with myocardial infarction (MI). Here, a MI mice model was established. One week after MI, mice were treated with saline or DAPA (1.5 mg/kg/day) for 4 weeks. At the end of this study, echocardiography was performed to assess cardiac structure and function. Myocardial apoptosis was analyzed by Western blot and immunofluorescence. Inflammatory cytokines and cardiac fibrosis were analyzed by real-time PCR and Masson's trichrome stain, respectively. Results showed that DAPA improved cardiac structure and function, attenuated cardiac fibrosis, and inhibited inflammatory cytokines and myocardial apoptosis. Moreover, the inhibition of PI3K/AKT/mTOR pathway might be related to the cardioprotective role of DAPA. These findings reveal that dapagliflozin is a potential therapeutic agent for MI patients without diabetes.

Cardioprotection of Klotho against myocardial infarction-induced heart failure through inducing autophagy.

Myocardial infarction (MI) is the most common cause of heart failure (HF) worldwide. The aim of this study was to investigate the role of Klotho in cardiac function and remodeling as well as its underlying mechanism in mice with MI-induced HF. For in vivo analyses, MI or sham MI were established in C57BL/6 mice. For in vitro analyses, the H9C2 cells were used to establish a model of oxygen glucose deprivation (OGD). The In vivo and in vitro models were treated with or without Klotho. 3-methyladenine (3-MA) was used to inhibit autophagy in MI mice and H9C2 cells. Cardiac function, cardiac fibrosis, cardiomyocyte autophagy, inflammatory cytokines and myocardial apoptosis were measured. Our results revealed that Klotho significantly improved cardiac function and remodeling, reduced cardiac fibrosis, and suppressed the levels of myocardial inflammatory factors and apoptosis in MI-induced HF model. Klotho enhanced autophagy in cardiomyocytes and inhibited PI3K/AKT/mTOR signaling pathway in the mouse model of MI. Similar observations were made in the OGD model after treatment with Klotho. However, the cardioprotective effects of Klotho was significantly suppressed by 3-MA. Our data indicate that Klotho exerts its cardioprotective effects against MI-induced HF by inducing autophagy through the inhibition of PI3k/AKT/mTOR signaling pathway.

Association between serum Klotho levels and the prevalence of diabetes among adults in the United States.

Background: Diabetes is a critical contributor to the pathogenesis of cardiovascular diseases. Klotho is an anti-aging protein with cardiovascular-renal protective effects. However, the relationship between serum Klotho levels and diabetes remains poorly understood. Objectives: This study aimed to investigate the relationship between serum Klotho levels and diabetes in US adults. Methods: We analyzed the cross-sectional data obtained from 13751 subjects aged 40-79 years in the National Health and Nutrition Examination Survey (NHANES) (2007-2016). Serum Klotho concentration was measured using an enzyme-linked immunosorbent assay (ELISA) and categorized into four quartiles (Q1-Q4). Multivariate logistic regression and restricted cubic spline (RCS) regression were conducted to explore the association between serum Klotho levels and the prevalence of diabetes. Results: As compared with quartile 1, serum Klotho levels in quartiles 2-4 yielded odds ratios (OR) (95% CI) of diabetes of 0.96 (0.80-1.15), 0.98 (0.82-1.18), and 1.25 (1.04-1.50), respectively, after covariate adjustment (P for trend = 0.018). The results implied an increased risk of diabetes. The RCS plot showed a U-shaped relationship linking serum Klotho levels with diabetes (P for nonlinearity = 0.003). Conclusions: In summary, a nonlinear and positive association was found between serum Klotho levels and the prevalence of diabetes. Further study is needed to verify the causality of this association and elucidate the underlying mechanisms.

Association between migraine and cardiovascular disease: A cross-sectional study.

Background: Cardiovascular disease (CVD) poses a tremendous threat to global health, giving rise to exceedingly high morbidity and mortality among patients. A migraine is a common neurological disorder characterized by recurrent attacks of severe headache, while its cardiovascular burden remains unclear. Therefore, this study aims to investigate whether migraine is associated with CVD. Methods: The cross-sectional data of 5,692 subjects aged 20 or above was obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. To determine whether migraine is associated with CVD, weighted logistic regression models were used. In a subsequent subgroup analysis, several confounding factors were also explored to investigate the association between migraine and CVD. Results: In total, 5,692 subjects were enrolled in this study, with the prevalence of CVD being 13.3%. Participants with CVD tended to be older, male, non-Hispanic whites, more educated, former smokers, and alcohol drinkers, and had a higher waist circumference, less physical activity, a higher level of triglyceride and creatinine as well as a lower level of high-density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) (all P < 0.05). Considering all potential confounders, migraine was associated with a higher risk of CVD [odds ratios (ORs) 2.77; 95% confidence intervals (CIs): 1.56-4.90]. Subgroup analysis showed a higher risk of CVD in females, those older than 60 years, with a lower body mass index (BMI) level (≤ 30 kg/m2), a higher level of eGFR (> 90 mL/min/1.73 m2), hypertension and hyperlipidemia and without diabetes. Conclusion: In summary, our study revealed a positive association between migraine with CVD in a nationally representative US adult population. Our findings highlighted that migraine should be considered an important risk factor for CVD.

Homeostatic neuro-metasurfaces for dynamic wireless channel management.

The physical basis of a smart city, the wireless channel, plays an important role in coordinating functions across a variety of systems and disordered environments, with numerous applications in wireless communication. However, conventional wireless channel typically necessitates high-complexity and energy-consuming hardware, and it is hindered by lengthy and iterative optimization strategies. Here, we introduce the concept of homeostatic neuro-metasurfaces to automatically and monolithically manage wireless channel in dynamics. These neuro-metasurfaces relieve the heavy reliance on traditional radio frequency components and embrace two iconic traits: They require no iterative computation and no human participation. In doing so, we develop a flexible deep learning paradigm for the global inverse design of large-scale metasurfaces, reaching an accuracy greater than 90%. In a full perception-decision-action experiment, our concept is demonstrated through a preliminary proof-of-concept verification and an on-demand wireless channel management. Our work provides a key advance for the next generation of electromagnetic smart cities.

Klotho improves cardiac fibrosis, inflammatory cytokines, ferroptosis, and oxidative stress in mice with myocardial infarction

The anti-aging protein Klotho has been associated with cardiovascular health protection. Nevertheless, the protective mechanism remains unknown. The present study is aimed at exploring the effect of Klotho on cardiac remodeling and its potential mechanism in mice with myocardial infarction (MI). We used left anterior coronary artery descending ligation to develop an MI model for in vivo analyses. In contrast, H9C2 cells and cardiac fibroblasts were used to establish the oxygen–glucose deprivation (OGD) model in in vitro analyses. In vivo and in vitro models were treated with Klotho. Compound C, an AMPK signaling inhibitor, was used to determine whether Klotho’s effects are mediated through the AMPK/mTOR signaling pathway. Echocardiography, Masson trichrome staining, immunofluorescence, immunohistochemistry, real-time polymerase chain reaction (RT-PCR), and western blot were used to detect the related indicators. The findings of the in vivo model indicate that Klotho treatment improved the mice’s cardiac function, reduced cardiac fibrosis, and attenuated myocardial inflammatory factors, ferroptosis, and oxidative stress. The results of the in vitro model were in line with the findings of in vivo modeling. An AMPK inhibitor, Compound C, reversed all these effects. In conclusion, Klotho potentially improves cardiac remodeling in MI mice by regulating AMPK/mTOR signaling, demonstrating Klotho as an effective MI therapeutic agent. (AU)