Intermittent hypoxia (IH)-induced cognition decline is related to the neuroinflammation in microglia. SUMOylation is associated with multiple human diseases, which can be reversed by sentrin/SUMO-specific proteases 1 (SENP1). Herein, we investigated the role of SENP1 in IH-induced inflammation and cognition decline. BV-2 microglial cells and mice were used for inflammatory response and cognition function evaluation following IH treatment. Biochemical analysis and Morris water maze methods were used to elaborate the mechanism of SENP1 in IH impairment. Molecular results revealed that IH induced the inflammatory response, as evidenced by the up-regulation of NF-κB activation, IL-1β and TNF-α in vitro and in vivo. Moreover, IH decreased the expression of SENP1, and increased the SUMOylation of NEMO, not NF-κB P65. Moreover, SENP1 overexpression inhibited IH-induced inflammatory response and SUMOylation of NEMO. However, the inhibitions were abolished by siRNA-NEMO. In contrast, SENP1 depletion enhanced IH-induced inflammatory response and SUMOylation of NEMO, accompanying with increased latency and reduced dwell time in mice. Overall, the results demonstrated that SENP1 regulated IH-induced neuroinflammation by modulating the SUMOylation of NEMO, thus activating the NF-κB pathway, revealing that targeting SENP1 in microglia may represent a novel therapeutic strategy for IH-induced cognitive decline.
  Cardioprotection by preventing or repairing mitochondrial damage is an unmet therapeutic need. To understand the role of cardiomyocyte mitochondria in physiopathology, the reliable characterization of the mitochondrial morphology and compartment is pivotal. Previous studies mostly relied on two-dimensional (2D) routine transmission electron microscopy (TEM), thereby neglecting the real three-dimensional (3D) mitochondrial organization. This study aimed to determine whether classical 2D TEM analysis of the cardiomyocyte ultrastructure is sufficient to comprehensively describe the mitochondrial compartment and to reflect mitochondrial number, size, dispersion, distribution, and morphology.
 
  Spatial distribution of the complex mitochondrial network and morphology, number, and size heterogeneity of cardiac mitochondria in isolated adult mouse cardiomyocytes and adult wild-type left ventricular tissues (C57BL/6) were assessed using a comparative 3D imaging system based on focused ion beam-scanning electron micr that BNIP3 deletion physiologically acts as a molecular brake on mitochondrial number, suggesting a role in mitochondrial fusion/fission processes and thereby regulating the homeostasis of cardiac bioenergetics.Although 3-year-old children sometimes simulate emotions to adapt to social norms, we do not know if even younger children can pretend emotions in playful contexts. The present study investigated (1) what emotions infants of 1-2 years old are capable of pretending and (2) the possible role of language and symbolic play in the ability to pretend emotions. The sample included 69 infants aged 18 to 31 months and their parents. Infants were administrated the Test of Pretend Play, and their parents responded to the MacArthur-Bates CDI-II inventory, part of the MacArthur-Bates CDI-I, and a questionnaire about the expression of pretend emotions. Results suggest that very young children simulate emotions. Furthermore, children's simulation of emotions was related to both symbolic play and language. Specifically, the ability to label emotions was linked to the ability to simulate them. The role of language and symbolic play in the development of the capacity to express and understand pretend emotions is discussed.
  Neuromyelitis optica spectrum disorder (NMOSD) is a rapidly disabling disease. Epidemiologic studies have suggested varying NMOSD mortality across ethnic groups.  https://www.selleckchem.com/products/apr-246-prima-1met.html  However, NMOSD mortality data in China are scarce. This study's objectives were to explore mortality and causes of death among Chinese NMOSD patients and to identify independent predictors of death.
 
  We performed a retrospective study with a 10-year follow-up of Chinese NMOSD patients. A Cox proportional hazards model was used to identify independent predictors of death.
 
  Five hundred and sixty-nine patients were included; 24 patients died during follow-up, for overall mortality of 4.2%. In these patients, the median disease duration at the time of death was 3.4years. The most common cause of death was secondary infection (62.5%), especially respiratory infection (45.8%). The second most common cause of death was extensive cervical myelitis with respiratory failure (16.7%). Other causes included suicide (8.3%), cancer (4.2%), cerebral embolism (4.2%), and unknown causes (4.2%). The multivariate Cox analyses indicated that a short first interattack interval (HR=0.93, 95% CI 0.89-0.98, p=0.003), lack of regular immunotherapy (HR=10.34, 95% CI 4.05-26.37, p<0.001), and older age at onset were independent predictors of death. Every increasing decade of onset age increased the risk of death 2.59 times (95% CI 1.74-3.86, p<0.001).
 
  Infections were more common in patients not treated with any immunotherapy, indicating that early and consequent immunotherapy might prevent death by infections, which is of great importance for further treatment of NMOSD patients to avoid undertreatment due to fear of treatment-associated infections.
 Infections were more common in patients not treated with any immunotherapy, indicating that early and consequent immunotherapy might prevent death by infections, which is of great importance for further treatment of NMOSD patients to avoid undertreatment due to fear of treatment-associated infections.Transfusion-related acute lung injury (TRALI) is a clinical syndrome which is associated with the formation of neutrophil extracellular trap (NET). Recent studies have demonstrated the roles of microRNAs (miRNAs) in the pathophysiological process of TRALI. Here, the study focused on the role of miR-144 and the molecular mechanisms in NET-induced TRALI. Up-regulated miR-144 and under-expressed KLF2 were determined in patients with TRALI. In the mouse model of a two-event TRALI induced by intraperitoneal injections with lipopolysaccharide and anti-H-2Kd mAb, we determined expression patterns of miR-144, Krüppel-like factor 2 (KLF2), chemokine (C-X-C motif) receptor 1 (CXCR1) and nuclear factor kappa-B (NF-kappaB) p65. The results confirmed that miR-144 was highly expressed, while KLF2 was poorly expressed in mice with TRALI. Dual-luciferase reporter gene assay identified that miR-144 could target KLF2. Using gain- and loss-of-function approaches, we analysed the effects of miR-144 and its interaction with KLF2 on TRALI.