YAP confers small cell lung cancer with the intratumoral heterogeneity and resistance to chemotherapy drugs.

Shear stress exerted by the blood stream modulates endothelial functions through altering gene expression. KLF2 and KLF4, the mechanosensitive transcription factors, are promoted by laminar flow to maintain endothelial homeostasis. However, how the expression of KLF2/4 is regulated by shear stress is poorly understood. Here, we showed that the activation of PIEZO1 upregulates the expression of KLF2/4 in endothelial cells. Mice with endothelial-specific deletion of Piezo1 exhibit reduced KLF2/4 expression in thoracic aorta and pulmonary vascular endothelial cells. Mechanistically, shear stress activates PIEZO1, which results in a calcium influx and subsequently activation of CaMKII. CaMKII interacts with and activates MEKK3 to promote MEKK3/MEK5/ERK5 signaling and ultimately induce the transcription of KLF2/4. Our data provide the molecular insight into how endothelial cells sense and convert mechanical stimuli into a biological response to promote KLF2/4 expression for the maintenance of endothelial function and homeostasis.

Several randomized controlled trials (RCTs) and observational studies have compared the efficacy of digital chest drainage system versus traditional chest drainage system. However, the results were inconsistent. We searched the Web of Science and Pubmed for observational studies and RCTs that compared the effect of digital chest drainage system with traditional chest drainage system after pulmonary resection. Eight studies (5 randomized control trails and 3 observational studies) comprising 1487 patients met the eligibility criteria. Compared with the traditional chest drainage system, digital chest drainage system reduced the risk of prolonged air leak (PAL) (RR = 0.54, 95%CI 0.40–0.73, p < 0.0001), and shortened the duration of chest drainage (SMD = − 0.35, 95%CI -0.60 - -0.09, p = 0.008) and length of hospital stay (SMD = − 0.35, 95%CI -0.61 - -0.09, p = 0.007) in patients after pulmonary resection. Digital chest drainage system is expected to benefit patients to attain faster recovery and higher life quality as well as to reduce the risk of postoperative complications. Further RCTs with larger sample size are still needed to more clearly elucidate the advantages of digital chest drainage system.

Aims: We aimed to investigate the effect and mechanism of pleiotropic chemokine CCL24 in heart failure. Methods and results: Compared with normal donators, the expression of CCL24 and number of cardiac M2 macrophages in heart were higher in heart failure patients, the same as plasma CCL24. Treatment with CCL24 antibody hindered Ang II (1500 ng/kg/min)–induced cardiac adverse remodeling through preventing cardiac hypertrophy and fibrosis. RNA-seq showed that CCL24/CCR3 axis was involved in immune and inflammatory responses. Single-cell analysis of cytometry by time of flight (CyTOF) revealed that CCL24 antibody decreased the M2 macrophage and monocyte polarization during Ang II stimulation. Immunofluorescence co-localization analysis confirmed the expression of CCR3 in macrophage and fibroblasts. Then, in vitro experiments confirmed that CCL24/CCR3 axis was also involved in cardiac primary fibroblast activation through its G protein–coupled receptor function. Conclusion: CCL24/CCR3 axis plays a crucial part in cardiac remodeling by stimulating M2 macrophage polarization and cardiac fibroblast activation. Graphical Cardiac M2 macrophages, CCL24 and circulation CCL24 increased in heart failure patients. Treatment with CCL24 Ab hindered Ang II induced cardiac structural dysfunction and electrical remodeling. In CCL24 Ab group RNA-seq found that it was related to immune responses and hypertrophic cardiomyopathy, CytoF revealed M2 macrophages and monocytes decreased obviously. In vitro,CCL24 promoted activation and migration of cardiac fibroblast.

Background: Observational studies suggest that sleep disturbances are commonly associated with schizophrenia. However, it is uncertain whether this relationship is causal. To investigate the bidirectional causal relation between sleep traits and schizophrenia, we performed a two-sample bidirectional Mendelian randomization (MR) study with the fixed effects inverse-variance weighted (IVW) method. Methods: As genetic variants for sleep traits, we selected variants from each meta-analysis of genome-wide association studies (GWASs) conducted using data from the UK Biobank (UKB). Results: We found that morning diurnal preference was associated with a lower risk of schizophrenia, while long sleep duration and daytime napping were associated with a higher risk of schizophrenia. Multivariable MR analysis also showed that sleep duration was associated with a higher risk of schizophrenia after adjusting for other sleep traits. Furthermore, genetically predicted schizophrenia was negatively associated with morning diurnal preference and short sleep duration and was positively associated with daytime napping and long sleep duration. Conclusions: Therefore, sleep traits were identified as a potential treatment target for patients with schizophrenia.