Emerging evidence shows that metabolic regulation may be a critical mechanism in B cell activation and function. As targets of several most widely used immunosuppressants, Ca²⁺ signaling and calcineurin may play an important role in regulating B cell metabolism. Here, we demonstrate that IP₃R-mediated Ca²⁺ signaling and calcineurin regulate B cell proliferation and survival by activating metabolic reprogramming in response to B cell receptor (BCR) stimulation. Both IP₃R-triple-knockout (IP₃R-TKO) and calcineurin inhibition dramatically suppress the metabolic switch in oxidative phosphorylation and glycolysis of stimulated B cells through regulation of glucose uptake, glycolytic enzyme expression, and mitochondrial remodeling, leading to impaired cell-cycle entry and survival. In addition, IP₃R-Ca²⁺ acts as a master regulator of the calcineurin-MEF2C-Myc pathway in driving B cell metabolic adaptations. As genetic defects of IP₃Rs were recently identified as a new class of inborn errors of immunity, these results have important implications for understanding the pathogenesis of such diseases.

Lung ageing alters the intrinsic structure of the lung and pulmonary surfactant system and increases the mortality and morbidity due to respiratory diseases in elderly individuals. We hypothesized that lung ageing results from an insufficiency of type II alveolar epithelial cells (AECIIs) in the lung tissue. Sirtuin 3 (SIRT3) is a member of the sirtuin family of proteins that promote longevity in many organisms. Increased SIRT3 expression has been linked to an extended lifespan in humans. Hence, we speculated that the overexpression of SIRT3 may help to ameliorate lung senescence and improve AECII function. AECIIs were isolated from young and old patients with pneumothorax caused by pulmonary bullae. The expression of SIRT3, manganese superoxide dismutase and catalase, as well as cell function and senescence indicators of young and old AECIIs, were measured before and after SIRT3 overexpression. After SIRT3 overexpression, the aged state of old AECIIs improved, and anti-apoptotic activity, proliferation and secretion were dramatically enhanced. Surfactant protein C (SPC), which is secreted by AECIIs, reduces alveolar surface tension, repairs the alveolar structure and regulates inflammation. SPC deficiency in patients is associated with increased inflammation and delayed repair. SIRT3 deacetylated forkhead box O3a, thereby protecting mitochondria from oxidative stress and improving cell function and the senescent state of old AECIIs. These findings provide a possible direction for ageing-delaying therapies and interventions for diseases of the respiratory system.

Gene therapy has received great attention as a therapeutic approach to improve cardiac function post-myocardial infarction (MI), but its limitation lies in the lack of targeting. This study explored the use of ultrasound-targeted microbubble destruction (UTMD) technique to deliver β-catenin gene to the myocardium, aiming to evaluate its efficacy in preventing cardiac dysfunction post-MI. A cationic microbubble solution containing β-catenin gene pcDNA3.1 plasmid was injected through the tail vein at a rate of 0.6 mL/h, and ultrasound beams were delivered to the heart using GE Vivid 7 Medical Ultrasound System M3s Transducer. Bioluminescence imaging was used to analyze the efficiency of UTMD gene transfection into the myocardium. β-catenin levels were detected by real-time polymerase chain reaction and western blot. Additionally, MI was induced in mice by surgical ligation of the left coronary artery, and cardiac function was evaluated using echocardiography at 14 and 28 days post-surgery. Masson’s trichrome staining was employed to determine infarct size. Blood vessel density was also measured. TUNEL assay was used to measure cardiomyocyte apoptosis. Furthermore, mouse cardiac stem cells were isolated using flow cytometry, and Giemsa stain was applied to evaluate the colony adhesion. UTMD delivered the gene to the heart with high efficiency and specificity in vivo. The β-catenin expression was significantly increased in the myocardium (P < 0.01). After MI, the β-catenin group exhibited a notable improvement in the gene therapy-induced neovascularization in the border zone (P < 0.01) and the number and function of cardiac stem cells (P < 0.01), and a significant decrease in cardiomyocyte apoptosis in the heart tissue (P < 0.01). β-catenin gene pre-treated with UTMD can reduce the impact of myocardial injury and promote cardiac self-repair after MI.