RESEARCH ON THE ENERGY ABSORPTION CHARACTERISTICS OF EXPANSION TUBE ENERGY ABSORBING ELEMENTS FOR RAIL VEHICLES

In this paper, the expansion tube type energy absorbing element was taken as the research object, and 9 samples were tested by automatic electro-hydraulic servo press and large drop hammer impact tester. Based on the experimental data and numerical simulation results, the effects of wall thickness, cone outer diameter and impact velocity on the energy absorption characteristics of energy absorbing components were studied. The test results show that the expansion tube type energy absorbing element is not sensitive to the impact speed. The ratio of the smooth crash force of the energy absorbing element under the drop hammer impact to the smooth crash force of the quasi-static compression is about 0.96～0.98; when the outer diameter of the cone is constant, the force of the energy absorbing element is substantially linear with the wall thickness of the expansion tube; when the wall thickness of the expansion tube is constant, the force of the energy absorbing element is approximately linear with the outer diameter of the cone, and with the outer diameter of the the cone increases, the amount of increase in the force tends to decrease. This paper provides a basis for the design of the expansion tube type energy absorbing element

Reversible Immortalization Enables Seamless Transdifferentiation of Primary Fibroblasts into Other Lineage Cells

Fibroblasts can be transdifferentiated directly into other somatic cells such as cardiomyocytes, hematopoietic cells, and neurons. An advantage of somatic cell differentiation without first generating induced pluripotent stem cells (iPSCs) is that it avoids contamination of the differentiated cells with residual iPSCs, which may cause teratoma. However, since primary fibroblasts from biopsy undergo senescence during repeated culture, it may be difficult to grow transdifferentiated cells in sufficient numbers for future therapeutic purposes. To circumvent this problem, we reversibly immortalized primary fibroblasts by using the piggyBac transposon to deliver the human telomerase reverse transcriptase (hTERT) gene hTERT plus SV40 Large T. Both approaches enabled fibroblasts to grow continuously without senescence, and neither caused teratoma formation in immunodeficient mice. However, fibroblasts immortalized with hTERT plus SV40 large T antigen accumulated chromosomal rearrangements, whereas fibroblasts immortalized with hTERT retained the normal karyotype. To transdifferentiate hTERT-immortalized fibroblasts into other somatic lineage cells, we transiently transfected them with episomal OCT4 and cultured them under neural cell growth condition with transposase to remove the transposon. Tripotent neural progenitor cells were seamlessly and efficiently generated. Thus, reversible immortalization of primary fibroblasts with hTERT will allow potential autologous cell-based therapeutics that bypass and simulate iPSC generation

Regulation of hepatic stellate cell proliferation and activation by glutamine metabolism

<div><p>Liver fibrosis is the excessive accumulation of extracellular matrix proteins, which is mainly caused by accumulation of activated hepatic stellate cells (HSCs). The mechanisms of activation and proliferation of HSCs, two key events after liver damage, have been studied for many years. Here we report a novel pathway to control HSCs by regulating glutamine metabolism. We demonstrated that the proliferation of HSCs is critically dependent on glutamine that is used to generate α-ketoglutarate (α-KG) and non-essential amino acid (NEAA). In addition, both culture- and in vivo-activated HSCs have increased glutamine utilization and increased expression of genes related to glutamine metabolism, including GLS (glutaminase), aspartate transaminase (GOT1) and glutamate dehydrogenase (GLUD1). Inhibition of these enzymes, as well as glutamine depletion, had a significant inhibitory effect on HSCs activation. In addition to providing energy expenditure, conversion of glutamine to proline is enhanced. The pool of free proline may also be increased via downregulation of POX expression. Hedgehog signaling plays an important role in the regulation of glutamine metabolism, as well as TGF-β1, c-Myc, and Ras signalings, via transcriptional upregulation and repression of key metabolic enzymes in this pathway. Finally, changes in glutamine metabolism were also found in mouse liver tissue following CCl4-induced acute injury. Conclusion: Glutamine metabolism plays an important role in regulating the proliferation and activation of HSCs. Strategies that are targeted at glutamine metabolism may represent a novel therapeutic approach to the treatment of liver fibrosis.</p></div

Gln metabolism enzyme inhibitors suppress HSCs proliferation.

<p>A&B, relative proliferation of LX2 cells (A) or primary HSCs (B) by BrdU staining assay. Cells were plated in complete medium and treated with Bptes (GLS inhibitor), EGCG (GLUD1 inhibitor) or AOAA (transaminase inhibitor) at different concentrations for 72 hrs.</p

Gln metabolism influences transactivation of HSCs.

<p>A, primary HSCs were cultured for 7 days with or without glutamine. Autofluorescence was assessed. B &C, primary HSCs were cultured with or without Gln, Bptes, or AOAA. D, LX2 cells were treated with MDI. Relative changes of mRNA expression of Gln metabolism genes were analyzed by real-time PCR. Immunocytochemistry was used to assess the expression of col1A1 at protein level.</p

Glutamine is essential for HSCs proliferation.

<p>A&B: relative proliferation of LX2 cells (A,B) or primary HSCs (D) by BrdU staining or cell counting (C). Cells were plated in complete medium or Gln deficient medium with or without α-KG, NEAA, or the mixture of the two. BrdU-positive cells were quantified per optical section. Relative BrdU-positive cells for each group were analyzed. Error bars represent s.d. of triplicate samples from a representative experiment. *P < 0.05.</p

Gln metabolism is reprogrammed by Hedgehog signaling, Ras, Myc and TGF-β1.

<p>Primary HSCs were treated with GDC-0449 (to inhibit SMO) (A), FTS (B) (Ras inhibitor), 10058-F4 (C) (Myc inhibitor). LX2 cells and MDI-pretreated LX2 cells were treated with TGF-β1. RT-PCR was used to analyze expression of glutamine metabolic enzyme genes.</p

Gln metabolism is reprogrammed during HSC transactivation.

<p>A, primary HSCs isolated from rats were cultured for 7 days. B, primary HSCs isolated from donor patients were cultured for 7 days. C, HSCs were isolated from control mice and mice with liver fibrosis induced by 8 weeks of CCl₄ treatment. Relative changes of mRNA expression of Gln metabolism genes were examined by RT-PCR.</p