Propofol inhibits neuroinflammation and metabolic reprogramming in microglia in vitro and in vivo

Microglial activation-induced neuroinflammation is closely related to the development of sepsis-associated encephalopathy. Accumulating evidence suggests that changes in the metabolic profile of microglia is crucial for their response to inflammation. Propofol is widely used for sedation in mechanically ventilated patients with sepsis. Here, we investigate the effect of propofol on lipopolysaccharide-induced neuroinflammation, neuronal injuries, microglia metabolic reprogramming as well as the underlying molecular mechanisms. The neuroprotective effects of propofol (80 mg/kg) in vivo were measured in the lipopolysaccharide (2 mg/kg)-induced sepsis in mice through behavioral tests, Western blot analysis and immunofluorescent staining. The anti-inflammatory effects of propofol (50 μM) in microglial cell cultures under lipopolysaccharide (10 ng/ml) challenge were examined with Seahorse XF Glycolysis Stress test, ROS assay, Western blot, and immunofluorescent staining. We showed that propofol treatment reduced microglia activation and neuroinflammation, inhibited neuronal apoptosis and improved lipopolysaccharide-induced cognitive dysfunction. Propofol also attenuated lipopolysaccharide-stimulated increases of inducible nitric oxide synthase, nitric oxide, tumor necrosis factor-α, interlukin-1β and COX-2 in cultured BV-2 cells. Propofol-treated microglia showed a remarkable suppression of lipopolysaccharide-induced HIF-1α, PFKFB3, HK2 expression and along with downregulation of the ROS/PI3K/Akt/mTOR signaling pathway. Moreover, propofol attenuated the enhancement of mitochondrial respiration and glycolysis induced by lipopolysaccharide. Together, our data suggest that propofol attenuated inflammatory response by inhibiting metabolic reprogramming, at least in part, through downregulation of the ROS/PI3K/Akt/mTOR/HIF-1α signaling pathway

Simulation of Spatters Sticking Phenomenon in Laser Powder Bed Fusion Process Using the Smoothed Particle Hydrodynamics Method

In this work, a smoothed particle hydrodynamics (SPH) method is developed to simulate the spattering phenomenon in the laser powder bed fusion (L-PBF) process. First, an experiment using the high-speed synchrotron X-ray full-field imaging is conducted to acquire in-situ images during the L-PBF process. Then, a scenario is selected from the X-ray image as a case study of the SPH model. In the case study, a particle is ejected and melted by the metal vapor, impacts with another particle, solidifies, and sticks to the other particle to form a rigid body. As a result, the trajectories of the two particles match well with the experimental observation. The evolution of velocity and temperature of the particle is extracted from the simulation for analysis. The SPH model can be a useful alternative to computational models of simulating the spattering phenomenon of L-PBF

Dynamic Colonization of Klebsiella pneumoniae Isolates in Gastrointestinal Tract of Intensive Care Patients

Gastrointestinal carriage is regarded as a major reservoir of K. pneumoniae infections, especially in intensive care patients. A total of 101 (95.3%) KPC-producing carbapenem-resistant K. pneumoniae (CRKP) isolates were identified among 106 CRKP isolates collected from stool samples of inpatients performing active rectal screening for carbapenem-resistant Enterobacteriaceae during hospitalization in the ICUs of a tertiary hospital between 2016 and 2017. Among them, six KPC-producing CRKP isolates from three patients (two isolates for each patient) were identified with distinct antibacterial susceptibility. Our findings showed that: (1) blaKPC–2 gene is predominant in CRKP strains isolated from the intensive care patients and can be incorporated into various plasmids that are transmissible among multiple bacterial hosts in the human gastrointestinal tract; (2) the human gastrointestinal tract has a capacity to dynamically colonize multiple clones of CRKP strains with varied plasmids, diverse antimicrobial resistance genes and virulence genes. K. pneumoniae colonization is an important step in progression to extraintestinal infection, which provides the rationale for establishing intervention measures to prevent subsequent infection. Thus, close surveillance on CRKP colonization, together with effective infection prevention and control measures, should be put into practice

First case of AML with rare chromosome translocations: a case report of twins

Abstract Background Leukemia is different from solid tumor by harboring genetic rearrangements that predict prognosis and guide treatment strategy. PML-RARA, RUNX1-RUNX1T1, and KMT2A-rearrangement are common genetic rearrangements that drive the development of acute myeloid leukemia (AML). By contrast, rare genetic rearrangements may also contribute to leukemogenesis but are less summarized. Case presentation Here we reported rare fusion genes ZNF717-ZNF37A, ZNF273-DGKA, and ZDHHC2-TTTY15 in a 47-year-old AML-M4 patient with FLT3 internal tandem duplication (ITD) discovered by whole genome sequencing (WGS) using the patient’s healthy sibling as a sequencing control. Conclusion This is, to our knowledge, the first case of AML with fusion gene ZNF717-ZNF37A, ZNF273-DGKA, and ZDHHC2-TTTY15

GPU-acceleration 3D rotated-staggered-grid solutions to microseismic anisotropic wave equation with moment tensor implementation

To improve the accuracy of microseismic inversion, seismic anisotropy and moment tensor source should be carefully considered in the forward modelling stage. In this study, 3D microseismic anisotropy wave forward modelling with a moment tensor source was proposed. The modelling was carried out based on a rotated-staggered-grid (RSG) scheme. In contrast to staggered-grids, the RSG scheme defines the velocity components and densities at the same grid, as do the stress components and elastic parameters. Therefore, the elastic moduli do not need to be interpolated. In addition, the detailed formulation and implementation of moment-tensor source loaded on the RSG was presented by equating the source to the stress increments. Meanwhile, the RSG-based 3D wave equation forward modelling was performed in parallel using compute unified device architecture (CUDA) programming on a graphics processing unit (GPU) to improve its efficiency. Numerical simulations including homogeneous and anisotropic models were carried out using the method proposed in this paper, and compared with other methods to prove the reliability of this method. Furthermore, the high efficiency of the proposed approach was evaluated. The results show that the computational efficiency of proposed method can be improved by about two orders of magnitude compared with traditional central processing unit (CPU) computing methods. It could not only help the analysis of microseismic full wavefield records, but also provide support for passive source inversion, including location and focal mechanism inversion, and velocities inversion

Isoschaftoside Inhibits Lipopolysaccharide-Induced Inflammation in Microglia through Regulation of HIF-1α-Mediated Metabolic Reprogramming

Isoschaftoside is a C-glycosyl flavonoid extracted from the root exudates of Desmodium uncinatum and Abrus cantoniensis. Previous studies suggested that C-glycosyl flavonoid has neuroprotective effects with the property of reducing oxidative stress and inflammatory markers. Microglia are key cellular mediators of neuroinflammation in the central nervous system. The aim of this study was to investigate the effect of isoschaftoside on lipopolysaccharide-induced activation of BV-2 microglial cells. The BV-2 cells were exposed to 10 ng/ml lipopolysaccharide and isoschaftoside (0–1000 μM). Isoschaftoside effectively inhibited lipopolysaccharide-induced nitric oxide production and proinflammatory cytokines including iNOS, TNF-α, IL-1β, and COX2 expression. Isoschaftoside also significantly reduced lipopolysaccharide-induced HIF-1α, HK2, and PFKFB3 protein expression. Induction of HIF-1α accumulation by CoCl2 was inhibited by isoschaftoside, while the HIF-1α specific inhibitor Kc7f2 mitigated the metabolic reprogramming and anti-inflammatory effect of isoschaftoside. Furthermore, isoschaftoside attenuated lipopolysaccharide-induced phosphorylation of ERK1/2 and mTOR. These results suggest that isoschaftoside can suppress inflammatory responses in lipopolysaccharide-activated microglia, and the mechanism was partly due to inhibition of the HIF-1α-mediated metabolic reprogramming pathway

Sensitivity parameters of tight sand gas: A case study of Lower Cretaceous Yingcheng Formation of Yingtai gas field in Songliao Basin, NE China

In tight sandstone, the gas-bearing sensitivity parameters are studied to improved prediction accuracy of thin gas layer due to the small impedance differences between gas-bearing layers and surrounding rocks. In this paper, we propose a new combined elastic parameter, i.e., the ratio of the first Lame coefficient to S-wave velocity based on elastic parameters sensitivity analysis for tight sandstone gas. By considering different geological conditions, we introduce the extending attribute (the ratio of Russell fluid phase to S-wave velocity), which can reduce to the ratio of the first Lame coefficient to S-wave velocity in specific condition. Both Gassmann equation and Brie empirical relationship are applied to calculate elastic parameters of different gas saturation in fluid replacement process. The results verify the validity of the new combined elastic parameter, which is more sensitive to gas saturation than conventional parameters, such as the product of the first Lame coefficient and density and the ratio of P-wave to S-wave velocity. The pre-stack inversion is applied in the second member of Lower Cretaceous Yingcheng Formation in Yingtai gas field. Compared to the section of the product for the first Lame coefficient and density, the results show the new combined elastic parameter presented improves the accuracy of identifying gas-bearing layers, well conforms to the logging interpretation, and greatly enhances the identification ability and prediction accuracy of gas-bearing layers. Key words: Tight sand gas, Gas-bearing, Elastic parameters, Sensitivity parameters, Pre-stack inversio

Pyrene exposure influences the thyroid development of Sebastiscus marmoratus embryos

National Natural Science Foundation of China [20977071]; Ocean Public Welfare Scientific Research Special Appropriation Project [201005016]; Fundamental Research Funds for the Central Universities [2012121045]Thyroid hormones play crucial roles in regulating development, morphogenesis, growth, and behavior in fishes. Some environmental pollutants have adverse effects on either development or function of the thyroid gland in fish. However, there are few reports on the effects of polycyclic aromatic hydrocarbons (PAHs) on fish thyroid. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to pyrene (Py) for 5 days at the concentrations of 0.5, 5, and 50 nmol/L. The results showed that Py exposure decreased the expression of thyroid primordium markers, Pax2.1 and Nk2.1a as detected by quantitative PCR and in situ hybridization, and reduced the concentration of T-3, but not T-4. Thyroid receptor genes (TR alpha and TR beta) expression was down-regulated by Py. At the same time, Py exposure impaired the expression of thyroid development related genes. Fgfr2 and Hoxa3a expression, and altered the mRNA levels of thyroid function related genes, Deio1, Ttr, and Tg. In conclusion, the results demonstrated Py exposure inhibited thyroid development and influenced the function of thyroid system in rockfish embryos. (c) 2012 Elsevier B.V. All rights reserved

Chronic exposure to paclobutrazol causes hepatic steatosis in male rockfish Sebastiscus marmoratus and the mechanism involved

Paclobutrazol (PBZ) is a triazole-containing fungicide which is widely used in agriculture. Acute toxicity can follow its extensive use but it is generally weaker than traditional pesticides such as organochlorine and organophosphorus. However, its adverse effects on aquatic organisms need to be investigated. This study was conducted to investigate the effect of PBZ exposure on the hepatic lipid metabolism of Sebastiscus marmoratus. After PBZ exposure for 50 days, hepatic lipid droplets were enlarged and the hepatic total lipid, triglyceride, total cholesterol and free fatty acid content had increased in a dose dependent manner compared to the control. The mRNA expression of lipid metabolism associated genes such as peroxisome proliferator-activated receptors (PPARs), androgen receptor, acetyl-CoA carboxylase 1, fatty acid synthesis, fatty acid bing protein 4, liver X receptor alpha (LXR alpha) and stearoyl-CoA desaturase were up-regulated by PBZ exposure. These results indicated that triazole-containing fungicides might affect the metabolism and health of fish via the multi-signal pathways of nuclear receptors such as PPARs and LXR. (c) 2012 Elsevier B.V. All rights reserved