Macrophage WNK1 senses intracellular hypo-chlorine to regulate vulnerability to sepsis attack during hypochloremia.

Sepsis is one of the leading causes of death in critical patients worldwide and its occurrence is related to the excessive activation of macrophages. Chloride loss worsens the prognosis of patients with sepsis but the underlying mechanism is currently unclear. In this study, we founded that macrophages deficient in intracellular Cl- secrete more inflammatory cytokines such as IL-1ß, IL-6 and TNF-α compared with control group. The intracellular chloride level decreased in WNK1 deficiency or activity inhibited macrophages with more severe inflammatory response after LPS treatment. Remimazolam, as classic GABAa receptor agonist, alleviates excessive inflammation cascade by promoting macrophage chloride influx during sepsis progression. Collectively, this study proves that macrophage WNK1 acts as a negative regulator of inflammatory response by sensing chloride to maintain intracellular chloride balance during sepsis coupled with hypochloremia.

Induced Mesenchymal Stem Cells-Small Extracellular Vesicles Alleviate Post-stroke Cognitive Impairment by Rejuvenating Senescence of Neural Stem Cells.

Ischemic stroke is typified by hypoxia and a cascade of pathophysiological events, including metabolic dysfunction, ionic dysregulation, excitotoxicity, inflammatory infiltration, and oxidative stress. These ultimately result in neuronal apoptosis or necrosis with constrained neuroregenerative capabilities. In this study, neural stem cells (NSCs) under conditions of oxygen-glucose deprivation (OGD) in vitro and following middle cerebral artery occlusion (MCAO) in vivo were explored. Transcriptome sequencing revealed a decline in NSC differentiation and neurogenesis after OGD exposure, which was related to cellular senescence. This observation was corroborated by increased senescence markers in the MCAO mouse model, reduction in NSC numbers, and decline in neurogenesis. Importantly, iMSC-sEVs (induced mesenchymal stem cells-small extracellular vesicles) have the therapeutic potential to alleviate NSC senescence and rejuvenate their regenerative capacities both in vitro and in vivo. Moreover, iMSC-sEVs contribute to the recovery of cognitive function and synapse loss caused by MCAO.

Effects of Different Injection Rates of Propofol on Postoperative Cognition in Elderly Patients Undergoing Laparoscopic Inguinal Hernia Repair.

Purpose: This study aimed to explore the effects of different injection rates of propofol on postoperative cognition in elderly patients undergoing laparoscopic inguinal hernia repair. Methods: A total of 180 elderly patients who planned to undergo laparoscopic inguinal hernia repair were randomly divided into three groups: slow injection of propofol (VS-Group, 30 mg kg-1 h-1); medium injection of propofol (VM-Group, 100 mg kg-1 h-1) or fast injection of propofol (VF-Group, 300 mg kg-1 h-1). Propofol was induced by microinfusion pump, and the depth of anesthesia was monitored by bispectral index (BIS). Propofol and remifentanil were continuously infused during anesthesia maintenance and adjusted according to BIS. The primary outcome was the use of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) to measure the incidence of postoperative cognitive decline (POCD) in elderly patients on the first and seventh postoperative day. Secondary outcomes included induced dose of propofol, incidence of burst suppression and maximum electroencephalographic (EEG) effect of propofol (BIS-min) during induction. Results: The incidence of POCD on the first and seventh day postoperatively was similar among the three groups (P > 0.05). However, with the increase of propofol injection rate, induced dose of propofol, incidence of burst suppression and BIS-min during induction, the number of patients requiring vasoactive agents were significantly increased (P < 0.001). Multivariate regression analysis showed that the brief duration of burst suppression during induction did not affect the occurrence of POCD, while age and duration of hospitalization were risk factors for POCD. Conclusion: For elderly patients undergoing laparoscopic inguinal hernia repair, lowering the injection rate of propofol (such as 30 mg kg-1 h-1) cannot decrease the incidence of early POCD, but reduces induction dose of propofol and use of vasoactive drugs, making the patient's hemodynamics more stable.

Relationship between climate and leaf carbon stable isotope of Hippophae.

We analyzed the relationship between carbon stable isotope characteristics of 131 Hippophae populations and environmental factors by measuring the foliar δ13C value in Hippophae. The results showed that the foliar δ13C values of Hippophae ranged from -24.65‰ to -29.11‰, with an average of -26.97‰. Hippophae species were C3 plants. For the foliar δ13C values, the coefficient variation at intraspecific level was higher than that at interspecific level, indicating that environmental factors should be main factors driving the variations of leaf δ13C. The δ13C values had no significant correlation with latitude and longitude, but were negatively correlated with altitude. The regression equation was δ13C(‰)=0.118VAP-0.007GST-0.000028RDA-20.721 (R2=0.212,P<0.0001). Water vapor pressure (VAP), growing season temperature (GST), and radiation (RDA) were the major factors affecting foliar δ13C values. Our results could provide a theoretical basis to understand the responses of Hippophae species to global climate change.