Interleukin-17 upregulation participates in the pathogenesis of heart failure in mice via NF-κB-dependent suppression of SERCA2a and Cav1.2 expression.

Interleukin-17 (IL-17), also called IL-17A, is an important regulator of cardiac diseases, but its role in calcium-related cardiac dysfunction remains to be explored. Thus, we investigated the influence of IL-17 on calcium handling process and its contribution to the development of heart failure. Mice were subjected to transaortic constriction (TAC) to induce heart failure. In these mice, the levels of IL-17 in the plasma and cardiac tissue were significantly increased compared with the sham group. In 77 heart failure patients, the plasma level of IL-17 was significantly higher than 49 non-failing subjects, and was negatively correlated with cardiac ejection fraction and fractional shortening. In IL-17 knockout mice, the shortening of isolated ventricular myocytes was increased compared with that in wild-type mice, which was accompanied by significantly increased amplitude of calcium transient and the upregulation of SERCA2a and Cav1.2. In cultured neonatal cardiac myocytes, treatment of with IL-17 (0.1, 1 ng/mL) concentration-dependently suppressed the amplitude of calcium transient and reduced the expression of SERCA2a and Cav1.2. Furthermore, IL-17 treatment increased the expression of the NF-κB subunits p50 and p65, whereas knockdown of p50 reversed the inhibitory effects of IL-17 on SERCA2a and Cav1.2 expression. In mice with TAC-induced mouse heart, IL-17 knockout restored the expression of SERCA2a and Cav1.2, increased the amplitude of calcium transient and cell shortening, and in turn improved cardiac function. In addition, IL-17 knockout attenuated cardiac hypertrophy with inhibition of calcium-related signaling pathway. In conclusion, upregulation of IL-17 impairs cardiac function through NF-κB-mediated disturbance of calcium handling and cardiac remodeling. Inhibition of IL-17 represents a potential therapeutic strategy for the treatment of heart failure.

Efficacy and safety of ultrasound-guided quadratus lumborum block in patients receiving percutaneous nephrolithotomy under general anaesthesia.

PURPOSE: The aim of this study was to explore the overall efficacy and safety of ultrasound-guided quadratus lumborum block combined with general anaesthesia in patients undergoing percutaneous nephrolithotomy (PCNL). METHODS: The study included 76 patients who underwent PCNL at our hospital between October 2018 and October 2019. The patients were randomly divided into the study group (ultrasound-guided quadratus lumborum block combined with general anaesthesia, 38 cases) and the control group (general anaesthesia, 38 cases). The intra-operative estimated blood loss, operative time and intra-operative anaesthetic usage were recorded. Moreover, the effective pressing times of the posterior cerebral artery (PCA) and the dosage of sufentanil in patient-controlled intravenous analgesia (PCIA) were observed within 48 hours after operation. RESULTS: The dosage of propofol and remifentanil, the time of intestinal exhaust recovery time and the hospital study in the study group were lower than those in the control group. The HR and MAP of the two groups, with a trend towards gradual decrease at T0 and T1, were lower than those at T0. At 2, 6, 8 and 24 hours after operation, the visual analogue scale/score (VAS) of the study group was lower than that of the control group. The analgesic rescue rate, the dosage of sufentanil and the effective PCA compression times in the study group were lower than those in the control group. The total incidence of adverse reactions in postanaesthesia care unit in the study group was significantly lower than that in the control group (8/38 vs 18/38). CONCLUSION: The combination of ultrasound-guided quadratus lumborum block and general anaesthesia effectively exerts beneficial outcomes in terms of validly reducing the dose of tranquilisers and anaesthetic analgesics during PCNL, which is able to treat patients with anaesthetic mode of low opioids.

Development of a base editor for convenient and multiplex genome editing in cyanobacteria.

Cyanobacteria are important primary producers, contributing to 25% of the global carbon fixation through photosynthesis. They serve as model organisms to study the photosynthesis, and are important cell factories for synthetic biology. To enable efficient genetic dissection and metabolic engineering in cyanobacteria, effective and accurate genetic manipulation tools are required. However, genetic manipulation in cyanobacteria by the conventional homologous recombination-based method and the recently developed CRISPR-Cas gene editing system require complicated cloning steps, especially during multi-site editing and single base mutation. This restricts the extensive research on cyanobacteria and reduces its application potential. In this study, a highly efficient and convenient cytosine base editing system was developed which allows rapid and precise C → T point mutation and gene inactivation in the genomes of Synechocystis and Anabaena. This base editing system also enables efficient multiplex editing and can be easily cured after editing by sucrose counter-selection. This work will expand the knowledge base regarding the engineering of cyanobacteria. The findings of this study will encourage the biotechnological applications of cyanobacteria.