Cdc42-mediated supracellular cytoskeleton induced cancer cell migration under low shear stress

Tumor microenvironment is composed of biological, chemical and physical factors. Mechanical factors are more and more focused these years. Therefore, mimicking mechanical factors' contribution to cancer cell malignancy will greatly improve the advance in this field. Although the induced malignant behaviors are present under many stimuli such as growth or inflammatory factors, the cell key physical migration mechanisms are still missing. In this study, we identify that low shear stress significantly promotes the formation of needle-shaped membrane protrusions, which is called filopodia and important for the sense and interact of a cell with extracellular matrix in the tumor microenvironment. Under low shear stress, the migration is promoted while it is inhibited in the presence of ROCK inhibitor Y27632, which could abolish the F-actin network. Using cell imaging, we further unravel that key to these protrusions is Cell division cycle 42 (Cdc42) dependent. After Cdc42 activation, the filopodia is more and longer, acting as massagers to pass the information from a cell to the microenvironment for its malignant phenotype. In the Cdc42 inhibition, the filopodia is greatly reduced. Moreover, small GTPases Cdc42 rather than Rac1 and Rho directly controls the filopodia formation. Our work highlights that low shear stress and Cdc42 activation are sufficient to promote filopodia formation, it not only points out the novel structure for cancer progression but also provides the experimental physical basis for the efficient drug anti-cancer strategies

Efficacy and safety of Qixue Tongzhi Granule in improving the exercise capacity of stable coronary artery disease: study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

BackgroundDespite optimal medical therapy, patients with stable coronary artery disease (SCAD) still have a high risk of recurrent cardiovascular events. Exercise capacity measured by cardiopulmonary exercise testing (CPET) is a good surrogate marker for the long-term prognosis of SCAD. Qixue Tongzhi Granule (QTG) is created by academician Chen Keji and has the function of tonifying qi, promoting blood circulation, and regulating qi-flowing. This trial aims to investigate the efficacy and safety of QTG in improving exercise tolerance, alleviating angina pectoris and anxiety/depression symptoms, promoting health-related quality of life, and reducing the risk of adverse cardiovascular events in subjects with SCAD.MethodsThis is a randomized, double-blind, placebo-controlled trial. 150 SCAD patients with qi deficiency, blood stasis, and liver qi stagnation syndrome are enrolled. Patients will be randomly allocated to the QTG or placebo groups at a 1:1 ratio. QTG and placebo will be added to the modern guideline-directed medical therapy for 12 weeks and patients will be followed up for another 24 weeks. The primary outcome is the improvement of metabolic equivalents measured by CPET. The secondary outcomes are cumulative incidence of composite endpoint events, other indicators in CPET, changes in the Seattle Angina Questionnaire, traditional Chinese medicine syndrome scale, 12 items of Short Form Health Survey Questionnaire, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7, changes of ST-T segment in the electrocardiogram, improvement of left ventricular ejection fraction and left ventricular end-diastolic diameter in echocardiography. In addition, metabolomics analysis will be performed based on blood samples. Adverse events and safety evaluations will also be documented. A full analysis set, per protocol set, and safety analysis set will be conducted.DiscussionThis clinical trial can enrich treatment options for CHD patients with low cardiorespiratory fitness and psychological imbalance, and it may also create a new situation for promoting the application of traditional Chinese medicine in cardiac rehabilitation.Clinical Trial Registration: [http://www.chictr.org.cn], identifier: [ChiCTR2200058988]

Research on Bearing Capacity of Angle Steel Transmission Tower Subject to Parallel Reinforcement by Fitting Channel Steel

[Introduction] The existing angle steel transmission tower has been running for many years, and the structural damage leads to the reduction of service performance. At the same time, the design bearing capacity of the old transmission tower ceases to meet the design requirements of the existing specifications. In order to address the insufficient bearing capacity of the old transmission tower, a parallel reinforcement method of angle steel fitted with channel steel is proposed. The bearing capacity of the reinforced structure is obtained through experimental research and finite element analysis (FEM), and the critical buckling load is proposed based on elastic analysis. [Method] In order to obtain the bearing capacity of members, two groups of axial compression tests on test specimens were set up. Two kinds of finite element numerical simulation include unreinforced angle steel and angle steel fitted with channel steel were conducted under axial compression. According to the failure mode, the calculation formula of buckling load of thin plate based on elastic analysis was deduced. [Result] The axial compression test results show the bending failure of the unreinforced angle steel specimen and the local buckling failure of the angle steel fitted with channel steel. The results also show that the bearing capacity of the reinforced members could be effectively improved. [Conclusion] Angle steel fitted with channel steel changes the instability failure state of the original angle steel and improves the bearing capacity of the angle steel. The established FEM can reflect the true failure state of the reinforced members, and the theoretical calculation formula can accurately calculate the axial compression bearing capacity of the reinforced members

Bone Mineral Density Reference Standards for Chinese Children Aged 3-18: Cross-Sectional Results of the 2013-2015 China Child and Adolescent Cardiovascular Health (CCACH) Study

Objectives: No nationwide paediatric reference standards for bone mineral density (BMD) are available in China. We aimed to provide sex-specific BMD reference values for Chinese children and adolescents (3-18 years). Methods: Data (10 818 participants aged 3-18 years) were obtained from cross-sectional surveys of the China Child and Adolescent Cardiovascular Health in 2015, which included four municipality cities and three provinces. BMD was measured using Hologic Discovery Dual Energy X-ray Absorptiometry (DXA) scanner. The DXA measures were modelled against age, with height as an independent variable. The LMS statistical method using a curve fitting procedure was used to construct reference smooth cross-sectional centile curves for dependent versus independent variables. Results: Children residing in Northeast China had the highest total body less head (TBLH) BMD while children residing in Shandong Province had the lowest values. Among children, TBLH BMD was higher for boys as compared with girls; but, it increased with age and height in both sexes. Furthermore, TBLH BMD was higher among US children as compared with Chinese children. There was a large difference in BMD for height among children from these two countries. US children had a much higher BMD at each percentile (P) than Chinese children; the largest observed difference was at P50 and P3 and the smallest difference was at P97. Conclusions: This is the first study to present a sex-specific reference dataset for Chinese children aged 3-18 years. The data can help clinicians improve interpretation, assessment and monitoring of densitometry results