3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) promotes invasion and activation of matrix metalloproteinases

BACKGROUND: Metastasis is a major cause of morbidity and mortality in breast cancer with tumor cell invasion playing a crucial role in the metastatic process. PDK1 is a key molecule that couples PI3K to cell proliferation and survival signals in response to growth factor receptor activation, and is oncogenic when expressed in mouse mammary epithelial cells. We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth and are highly invasive when grown on Matrigel. These properties correlate with induction of MMP-2 activity, increased MT1-MMP expression and a unique gene expression profile. METHODS: Invasion assays in Matrigel, MMP-2 zymogram analysis, gene microarray analysis and mammary isografts were used to characterize the invasive and proliferative function of cells expressing PDK1. Tissue microarray analysis of human breast cancers was used to measure PDK1 expression in invasive tumors by IHC. RESULTS: Enhanced invasion on Matrigel in PDK1-expressing cells was accompanied by increased MMP-2 activity resulting from stabilization against proteasomal degradation. Increased MMP-2 activity was accompanied by elevated levels of MT1-MMP, which is involved in generating active MMP-2. Gene microarray analysis identified increased expression of the ECM-associated genes decorin and type I procollagen, whose gene products are substrates of MT1-MMP. Mammary fat pad isografts of PDK1-expressing cells produced invasive adenocarcinomas. Tissue microarray analysis of human invasive breast cancer indicated that PDK1pSer241 was strongly expressed in 90% of samples. CONCLUSION: These results indicate that PDK1 serves as an important effector of mammary epithelial cell growth and invasion in the transformed phenotype. PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collagen. The presence of increased PDK1 expression in the majority of invasive breast cancers suggests its importance in the metastatic process

Research on the Experimental Teaching Method of Vibration Damping Fastener for Undergraduates Majoring in Rail Transit

Experiment is an important teaching link in talent training. Aiming at the current situation and problems of the experimental teaching of rail transit major, taking the experimental teaching of vibration damping fastener drop weight for railway engineering major of Central South University as an example, the specific methods of the new experimental teaching mode for undergraduates majoring in rail transit are expounded: Improve the subject experimental system, build an open experimental platform, and improve the school-enterprise resource sharing system, etc. This model is conducive to the reform and development of the experimental teaching model for rail transit majors and related science and engineering majors

Research on Practical Teaching of Railway Engineering Specialty Based on Temperature Test of Rubber Sleepers

Experimental teaching plays an important role in cultivating college students' innovative ability. This paper takes the practical teaching of the temperature test of the new rubber sleeper as an example to analyze the current situation and problems of the practical teaching of railway engineering. The specific measures of the new system of practical teaching of railway engineering are put forward: Build a practical teaching curriculum system, improve the practical teaching evaluation mechanism, and promote the sharing of school-enterprise resources, so as to cultivate outstanding railway engineering talents with engineering ability and innovative spirit

Bioinspired cellulose-integrated MXene-based hydrogels for multifunctional sensing and electromagnetic interference shielding

Bioinspired hydrogels are complex materials with distinctive properties comparable to biological tissues. Their exceptional sensitivity to various external stimuli leads to substantial application potential in wearable smart devices. However, these multifaceted hydrogels are often challenging to be combined with pattern customization, stimulus responsiveness, self-healing, and biocompatibility. Herein, inspired by mussel secretions, a printable, self-healing, and biocompatible MXene-based composite hydrogel was designed and prepared by incorporating Ti3C2Tx MXene nanosheets into the hydrogel framework through the chelation of calcium ions (Ca2+) with polyacrylic acid and cellulose nanofibers at alkaline conditions. The biocompatible conductive hydrogel exhibited sensitivity (gauge factor of 2.16), self-healing (within 1 s), recognition, and adhesion, distinguishing it as an ideal candidate for wearable multifunctional sensors toward strain sensing, vocal sensing, signature detection, and Morse code transmission. Additionally, the multifunctional hydrogel manifested efficient electromagnetic interference shielding properties (reaching more than 30 dB at a thickness of 2.0 mm), protecting electronics and humans from electromagnetic radiation and pollution. Therefore, the presented work represents a versatile strategy for developing environmentally friendly conductive hydrogels, demonstrating the perspectives of intelligent hydrogels for multifunctional applications

TRANSIENT VOLTAGE SUPPRESSOR BASED ON DIODE-TRIGGERED LOW-VOLTAGE SILICON CONTROLLED RECTIFIER

Transient voltage suppressor (TVS) has been widely used for electronic system ESD protection. A good TVS is usually costive as it needs some special processes and with extra masking layers for fabrication. A novel TVS design based on the standard CMOS process will be much attractive. This work proposes a new TVS device using a CMOS compatible diode-triggered silicon controlled rectifier (DLVTSCR) as the core device. Due to the available of multiple trigger mechanisms and the dual current paths for bypassing the ESD current, the newly proposed device is able to sink an ESD current of over 10 A. In addition, the holding voltage is promoted up to 6.83 V and the trigger voltage is lowered down to 10.8 V which is well suit for most portable device applications

Managerial drivers of Chinese labour loyalty in international construction projects

Organization performance is becoming ever more dependent on employee loyalty in the international con­struction projects. However, the improvement of construction labour loyalty on construction sites remains a largely neglected measure for reducing their turnover and improving their productivity. The purpose of this study was to quan­titatively investigate the managerial drivers of labour loyalty, including macro-environment of the project host country, organizational living environment, job system, rewards, and communication, and to explore the significance of satisfac­tion as a mediating variable in the relationship between the managerial drivers and construction labour loyalty. First, hypotheses on the relationships between construction labour loyalty, satisfaction and the five managerial drivers were proposed. Second, structural equation modelling was adopted to test these hypotheses. Finally, the results demonstrated two types of influence paths: (1) macro-environment, job system and communication have significantly direct effects on construction labour loyalty, (2) mediated by satisfaction, organizational living environment and rewards offer posi­tive indirect effects on construction labour loyalty. The first type of path serves as a long-term strategic orientation for improving labour loyalty. The second type of path is a tactic for short-term goals of labour loyalty enhancement. The research results can contribute to the body of knowledge of human resource management and the practice of enhancing labour productivity through improving construction labour loyalty in the context of international construction projects