Background: Heart failure with preserved ejection fraction (HFpEF) is a difficult disease with high morbidity and mortality rates and lacks an effective treatment. Here, we report the therapeutic effect of dapagliflozin, a sodiumglucose cotransporter 2 inhibitor (SGLT2i), on hypertension + hyperlipidemia-induced HFpEF in a pig model. Methods: HFpEF pigs were established by infusing a combination of deoxycorticosterone acetate (DOCA) and angiotensin II (Ang II), and Western diet (WD) feeding for 18 weeks. In the 9th week, half of the HFpEF pigs were randomly assigned to receive additional dapagliflozin treatment (10 mg/day) by oral gavage daily for the next 9 weeks. Blood pressure, lipid levels, echocardiography and cardiac hemodynamics for cardiac structural and functional changes, as well as epinephrine and norepinephrine concentrations in the plasma and tissues were measured. After sacrifice, cardiac fibrosis, the distribution of tyrosine hydroxylase (TH), inflammatory factors (IL-6 and TNF-α) and NO-cGMP-PKG pathway activity in the cardiovascular system were also determined. Results: Blood pressure, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) were markedly increased in HFpEF pigs, but only blood pressure was significantly decreased after 9 weeks of dapagliflozin treatment. By echocardiographic and hemodynamic assessment, dapagliflozin significantly attenuated heart concentric remodeling in HFpEF pigs, but failed to improve diastolic function and compliance with the left ventricle (LV). In the dapagliflozin treatment group, TH expression and norepinephrine concentration in the aorta were strongly mitigated compared to that in the HFpEF group. Moreover, inflammatory cytokines such as IL-6 and TNF-α in aortic tissue were markedly elevated in HFpEF pigs and inhibited by dapagliflozin. Furthermore, the reduced expression of eNOS and the PKG-1 protein and the cGMP content in the aortas of HFpEF pigs were significantly restored after 9 weeks of dapagliflozin treatment. Conclusion: 9 weeks of dapagliflozin treatment decreases hypertension and reverses LV concentric remodeling in HFpEF pigs partly by restraining sympathetic tone in the aorta, leading to inhibition of the inflammatory response and NO-cGMP-PKG pathway activation.

Four of the five major sensory systems (vision, olfaction, somatosensation, and audition) are thought to use different but partially overlapping sets of neurons to form unique representations of vast numbers of stimuli. The only exception is gustation, which is thought to represent only small numbers of basic taste categories. However, using new methods for delivering tastant chemicals and making electrophysiological recordings from the tractable gustatory system of the moth Manduca sexta, we found chemical-specific information is as follows: (1) initially encoded in the population of gustatory receptor neurons as broadly distributed spatiotemporal patterns of activity; (2) dramatically integrated and temporally transformed as it propagates to monosynaptically connected second-order neurons; and (3) observed in tastant-specific behavior. Our results are consistent with an emerging view of the gustatory system: rather than constructing basic taste categories, it uses a spatiotemporal population code to generate unique neural representations of individual tastant chemicals.

Myocardial infarction is one of the most threatening cardiovascular diseases for human beings. With the rapid development of wearable devices and portable electrocardiogram (ECG) medical devices, it is possible and conceivable to detect and monitor myocardial infarction ECG signals in time. This paper proposed a multi-channel automatic classification algorithm combining a 16-layer convolutional neural network (CNN) and long-short term memory network (LSTM) for I-lead myocardial infarction ECG. The algorithm preprocessed the raw data to first extract the heartbeat segments; then it was trained in the multi-channel CNN and LSTM to automatically learn the acquired features and complete the myocardial infarction ECG classification. We utilized the Physikalisch-Technische Bundesanstalt (PTB) database for algorithm verification, and obtained an accuracy rate of 95.4%, a sensitivity of 98.2%, a specificity of 86.5%, and an F1 score of 96.8%, indicating that the model can achieve good classification performance without complex handcrafted features.