Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is a severe clinical syndrome with mortality rate as high as 30-40%. There is no treatment yet to improve pulmonary endothelial ...barrier function in patients with severe pulmonary edema. Developing therapies to protect endothelial barrier integrity and stabilizing gas exchange is getting more and more attention. Sphingosine-1-phosphate (S1P) is able to enhance the resistance of endothelial cell barrier. S1P at physiological concentrations plays an important role in maintaining endothelial barrier function. Proliferation, regeneration and anti-inflammatory activity that mesenchymal stem cells (MSCs) exhibit make it possible to regulate the homeostatic control of S1P.
By building a pulmonary endothelial cell model of acute injury, we investigated the regulation of S1P receptors and sphingosine kinases expression by MSCs during the treatment of acute lung injury using RT-PCR, and investigated the HPAECs Micro-electronics impedance using Real Time Cellular Analysis.
It was found that the down-regulation of TNF-
expression was more significant when MSC was used in combination with S1P. The combination effection mainly worked on S1PR2, S1PR3 and SphK2. The results show that when MSCs were used in combination with S1P, the selectivity of S1P receptors was increased and the homeostatic control of S1P concentration was improved through regulation of expression of S1P metabolic enzymes.
The study found that, as a potential treatment, MSCs could work on multiple S1P related genes simultaneously. When it was used in combination with S1P, the expression regulation result of related genes was not simply the superposition of each other, but more significant outcome was obtained. This study establishes the experimental basis for further exploring the efficacy of improving endothelial barrier function in acute lung injury, using MSCs in combination with S1P and their possible synergistic mechanism.
A novel lytic Salmonella bacteriophage was isolated by using Klebsiella pneumoniae as host cells. The phage's genome was determined to be 47,564 bp and has the highest similarity to Salmonella phage ...E1 and Salmonella phage 64795_sal3, with coverages of 61% and 56%, respectively. Here, we announce the phage's complete genome.
We isolated a K47-type
Klebsiella pneumoniae
phage from untreated hospital sewage: vB_KpnP_IME305 (GenBank no. OK149215). Next-generation sequencing (NGS) demonstrated that IME305 has a ...double-stranded DNA genome of 38,641 bp with 50.9% GC content. According to BLASTn comparisons, the IME305 genome sequence shares similarity with that of
Klebsiella
phage 6998 (97.37% identity and 95% coverage). IME305 contains 45 open reading frames (ORFs) and no rRNA, tRNA, or virulence-related gene sequences. Bioinformatic analysis showed that IME305 belongs to the phage subfamily
Studiervirinae
and genus
Teetrevirus
.
To evaluate the auxiliary diagnostic value of Japanese respiratory society (JRS) scoring system for the rapid diagnosis of Mycoplasma pneumoniae pneumonia (MP) in inpatients with community acquired ...pneumonia (CAP).
The clinical data of inpatients with CAP between January 2013 and Novermber 2013 were retrospectively analyzed. The gold standard for identification of MP infection was determined by both positive culture and real time polymerase chain reaction (PCR) methods. Blood and sputum culture were used to detect other bacteria and fungi, and real time PCR to detect Chlamydia and Legionella pneumonia and the common respiratory viruses. Diagnostic test results consistency inspection was performed by Kappa test and continuous variable analysis was performed using t test.
Data from 139 CAP inpatients were analyzed. An aetiological diagnosis was made for 61 patients (43.9%). Thirty-five cases (25.2%) were diagnosed as MP infection by the gold standard, while 72 cases (52.0%) by the JRS scoring system. The sensit
Torque teno virus (TTV) has been found to be prevalent world-wide in healthy populations and in patients with various diseases, but its etiological role has not yet been determined. Using ...high-throughput unbiased sequencing to screen for viruses in the serum of a patient with persistent high fever who died of suspected viral infection and prolonged weakness, we identified the complete genome sequence of a TTV (isolate Hebei-1). The genome of TTV-Hebei-1 is 3649 bp in length, encoding four putative open reading frames, and it has a G+C content of 49%. Genomic comparison and a BLASTN search revealed that the assembled genome of TTV-Hebei-1 represented a novel isolate, with a genome sequence that was highly heterologous to the sequences of other reported TTV strains. A phylogenetic tree constructed using the complete genome sequence showed that TTV-Hebei-1 and an uncharacterized Taiwanese strain, TW53A37, constitute a new TTV genotype. The patient was strongly suspected of carrying a viral infection and died eventually without any other possible causes being apparent. No virus other than the novel TTV was identified in his serum sample. Although a direct causal link between the novel TTV genotype infection and the patient’s disease could not be confirmed, the findings suggest that surveillance of this novel TTV genotype is necessary and that its role in disease deserves to be explored.
Summary
Effective control of mode transition is one of the key technologies for dual‐mode scramjet. In this study, a 3‐dimensional unsteady Reynolds‐averaged Navier‐Stokes modeling was used to ...investigate the effects of equivalence ratio, inflow temperature, and pilot hydrogen on transient process of mode transition in a dual‐mode scramjet combustor. The isolator entrance Mach number was 2.5, and the fuel of vaporized kerosene was used in the combustor with pilot hydrogen. The results showed that during mode transition from ram mode to scram mode induced by reducing the equivalence ratio of kerosene, the disappearance of the high‐pressure zone around the kerosene injector was the sign of approaching the achievement of mode transition. The leading edge of the shock train moved downstream and the strength of shock train was significantly weakened. During this process, the distribution of heat release zone transformed from scattered along the combustor to being concentrated in the cavity. Then, the opposite process was studied when the inflow temperature was reduced from 1750 to 1000 K while the equivalence ratio was kept the same. The thickness of shear layers originated from the fuel injectors significantly increased. Altering the amount of pilot hydrogen can significantly influence the flow field in the combustor. It showed that the increase of pilot hydrogen could shield the kerosene vapor entering into the high‐temperature zone in the cavity and hindered the formation of concentrated heat release. Thus, the overall heat release became more dispersed.
The performance of a ball bearing–rotor system is often limited by the occurrence of subharmonic resonance with considerable vibration and noise. In order to comprehend the inherent mechanism and the ...feature of the subharmonic resonance, a symmetrical rotor system supported by ball bearings is studied with numerical analysis and experiment in this paper. A 6DOF rotordynamic model which includes the non-linearity of ball bearings, Hertzian contact forces and bearing internal clearance, and the bending vibration of rotor is presented and an experimental rig is offered for the research of the subharmonic resonance of the ball bearing–rotor system. The dynamic response is investigated with the aid of orbit and amplitude spectrum, and the non-linear system stability is analyzed using the Floquet theory. All of the predicted results coincide well with the experimental data to validate the proposed model. Numerical and experimental results show that the resonance frequency is provoked when the speed is in the vicinity of twice synchroresonance frequency, while the rotor system loses stability through a period-doubling bifurcation and a period-2 motion i.e. subharmonic resonance occurs. It is found that the occurrence of subharmonic resonance is due to the together influence of the non-linear factors, Hertzian contact forces and internal clearance of ball bearings. The effect of unbalance load on subharmonic resonance of the rotor system is minor, which is different from that of the sliding bearing–rotor system. However, the moment of couple has an impact influence on the subharmonic resonances of the ball bearing–rotor system. The numerical and experimental results indicate that the subharmonic resonance caused by ball bearings is a noticeable issue in the optimum design and failure diagnosis of a high-speed rotary machinery.
► A 6DOF non-linear model of a symmetrical ball bearing–rotor system is presented. ► An experimental rig is offered for the research of the subharmonic resonance. ► The subharmonic resonance occurs due to Hertzian contact forces and internal clearance. ► The moment of couple has an impact influence on the subharmonic resonance.
Oncolytic viruses are able to lyse tumor cells selectively in the liver without killing normal hepatocytes, in addition to activating the immune response. Oncolytic virus therapy is expected to ...revolutionize the treatment of liver cancer, including hepatocellular carcinoma (HCC), one of the most frequent and fatal malignancies. In this study, reverse genetics techniques were exploited to load NA fragments of the A/PuertoRico/8/34 virus (PR8) with GV1001 peptides derived from human telomerase reverse transcriptase. An
assessment of the therapeutic effect of the recombinant oncolytic virus was followed by an
study in mice with HCC. The recombinant virus was verified by sequencing of the recombinant viral gene sequence, and viral virulence was detected by hemagglutination assays and based on the 50% tissue culture infectious dose (TCID
). The morphological structure of the virus was observed by electron microscopy, and GV1001 peptide was localized by cellular immunofluorescence. The selective cytotoxicity of the recombinant oncolytic virus
was demonstrated in cultured HCC cells and normal hepatocytes, as only the tumor cells were killed; the normal cells were not significantly altered. Consistent with the
results, the recombinant oncolytic influenza virus significantly inhibited liver tumor growth in mice
, in addition to inducing an antitumor immune response, including an increase in the number of CD4
and CD8
T lymphocytes and, in turn, improving survival. Our results suggest that oncolytic influenza virus carrying GV1001 is a promising immunotherapy in patients with HCC.