Metformin promotes apoptosis of A549 cells via regulation of p-AMPK protein expression, bax/bcl-2 ratio and ROS levels

Purpose: To investigate the influence of metformin on apoptosis of pulmonary carcinoma cells (A549), and the associated mode of action.Methods: Pulmonary carcinoma cells in logarithmic growth phase were treated with graded concentrations of metformin, and the anti-proliferative and apoptotic effects of the drug were measured using MTT assay and flow cytometry, respectively. The levels of reactive oxygen species (ROS) in A549 cell suspension were determined with 2, 7- dihydrodichlorofluorescein diacetate (DCFH-DA) assay. The expression levels of phosphorylated AMP-activated protein kinase (p-AMPK), mammalian target of rapamycin (mTOR), and bax/bcl-2 ratio were measured using Western blotting and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR).Results: Metformin significantly promoted A549 cell apoptosis, but suppressed its proliferative potential in a dose- and time-based fashion. The levels of ROS, superoxide anion and MDA in A549 cells were significantly and dose-dependently increased by metformin (p < 0.05). Moreover, metformin markedly upregulated the mRNA and protein expressions of p-AMPK as well as bax/bcl-2 ratio, but had no impact on the expression level of mTOR (p < 0.05).Conclusion: Metformin promotes apoptosis in A549 cells via regulation of p-AMPK protein expression, bax/bcl-2 ratio, and ROS levels, and hence may play a role in lung cancer therapy

Intrinsic FGFR2 and Ectopic FGFR1 Signaling in the Prostate and Prostate Cancer

Advanced castrate-resistant prostate cancer (CRPC) is a poorly prognostic disease currently lacking effective cure. Understanding the molecular mechanism that underlies the initiation and progression of CRPC will provide new strategies for treating this deadly disease. One candidate target is the fibroblast growth factor (FGF) signaling axis. Loss of the intrinsic FGF7/FGF10-type 2 FGF receptor (FGFR2) pathway and gain of the ectopic type 1 FGF receptor (FGFR1) pathway are associated with the progression to malignancy in prostate cancer (PCa) and many other epithelial originating lesions. Although FGFR1 and FGFR2 share similar amino acid sequences and structural domains, the two transmembrane tyrosine kinases elicit distinctive, even sometime opposite signals in cells. Recent studies have revealed that the ectopic FGFR1 signaling pathway contributes to PCa progression via multiple mechanisms, including promoting tumor angiogenesis, reprogramming cancer cell metabolism, and potentiating inflammation in the tumor microenvironment. Thus, suppression of FGFR1 signaling can be an effective novel strategy to treat CRPC

The importance of knowledge and trust for ethical fashion consumption

Purpose. The clothing industry is one of the most polluting industries in the world, although manufacturers and retailers are trying to revert this tendency by applying ethical fashion principles. Drawing on the knowledge-attitude-behavior (KAB) model or practice, this study aims to predict Chinese consumers' purchase intention of ethical fashion by employing and extending the theory of planned behavior (TPB). Design/methodology/approach. The extended TPB model incorporates knowledge of ethical fashion and trust in the fashion industry and two critical variables in ethical fashion literature to explain the purchase intention of ethical fashion. Primary data from 245 Chinese respondents were collected in 2019. The model was tested and analyzed through structural equation modeling (SEM). Findings. Results show that the extended TPB model has higher predictability than the original TPB model. Attitude toward ethical fashion and subjective norm significantly predicts purchase intention while perceived behavioral control (PBC) does not. In addition, trust of ethical fashion is positively related to attitude toward ethical fashion and purchase intention, whereas knowledge of ethical fashion plays a significant role in predicting trust and the three TPB factors. The subjective norm was found to have the most significant impact on consumers' intention to purchase ethical fashion, which shows that social pressure from one individual's reference group is the most dominant factor in forming consumer's purchase intention on ethical fashion. Originality/value. The findings enrich the past literature on ethical fashion that trusting belief is a salient determinant of consumers' attitude toward ethical fashion and purchase intention of ethical fashion products. The findings also supported the applicability of KAB and TPB in the domain of ethical consumption in the context of a developing country

Establishment of OPG Transgenic Mice and the Effect of OPG on Bone Microarchitecture

Osteoprotegerin (OPG) plays a determinant role in regulating bone metabolism, but the effect of OPG on bone microarchitecture needs to be further elucidated. We attempted to construct pCI-hOPGp-mOPG vector containing human OPG promoter and FLAG tag and to microinject vector into fertilized zygotes from C57BL/6J × CBA mice to prepare transgenic mice. The OPG transgenic positive mice were identified by PCR and western blotting. Twelve-week-old OPG transgenic mice (OPG-Tg mice) and wild-type mice (WT mice) were utilized in the study of bone microarchitecture. Microcomputed tomography (micro-CT) data showed that compared with WT mice, the tibia of OPG-Tg mice showed an increased volumetric BMD (vBMD), tissue BMD (tBMD), trabecular thickness (Tb.Th), and trabecular number (Tb.N), and a decreased trabecular separation (Th.Sp) (P<0.05) . The cortical bone microarchitecture parameters, such as cortical area (Ct.Ar), cortical thickness (Ct.Th), cortical BMD (Ct.BMD), cortical BMC (Ct.BMC), BMD, and BMC of femur, were increased, and the inner perimeter (In.Pm) was decreased, in OPG-Tg mice, compared to those in WT mice (P<0.05). The established OPG transgenic mouse model could be valuable for further studying the biological significance and gene regulation of OPG in vivo

WTC2005-63258 RESEARCH ON THE IDENTIFICATION METHODS OF FRICTION IN KINEMATICAL JOINTS OF MECHANICAL SYSTEMS

ABSTRACT This paper describes two approaches for the simultaneous identification of the coulomb and viscous parameters in kinematical joints. One is a time-domain method (TDM) and the other is a frequency-domain method (FDM). Simulation shows that both of the two methods have good performances in identifying friction at high SNR (90dB). But at low SNR (20dB), the estimation accuracy of the frequency-domain method is higher than that of the time-domain method. A field experiment employing a linkage mechanism driven by motor is also carried out. The experimental results obtained by the two approaches are almost identical under different experiment conditions. It has been concluded that the presented identification methods of friction in kinematical joints are correct and applicable. INTRODUCTION Kinematical joint is an absolutely necessary structural connection in mechanical systems. The kinematical joint is responsible for transferring energy to a remote site, and may change the type of motion, as needed. The characteristics of kinematical joints have been studied in many paper

Morphology and Molecular Analysis of Moesziomyces antarcticus Isolated From the Blood Samples of a Chinese Patient

Objective: To identify the pathogen causing fungemia in a Chinese patient and describe its morphological and molecular characterizes.Methods: Samples of central and peripheral venous blood were collected for blood culture. Morphology and drug sensitivities of the isolated yeast-like fungus were analyzed. rDNA sequencing and molecular phylogenetic analysis of the isolated strains were performed using DNAMAN and MEGA software.Results: A strain of yeast-like fungi was repeatedly isolated from blood samples of a Chinese patient. The isolates grew well on sabouraud medium broth plate. The colonies were smooth and round at 28°C, and were of rough surface and irregular shape at 35°C. Molecular phylogenetic trees constructed based on the internal transcribed spacer (ITS) and D1/D2 domains of 28S rDNA gene demonstrated the isolated yeast-like fungus was Moesziomyces antarcticus. Drug susceptibility test showed that this isolated M. antarcticus was resistant or had relatively low susceptibility to flucytosine, fluconazole, voriconazole, and itraconazole, and only sensitive to amphotericin.Conclusion: This study provided more information for the molecular and morphology characteristics of M. antarcticus and reviewed the species information of Moesziomyces associated with human infections, which will contribute to the identification and diagnosis of Moesziomyces infections

Fuzzy-NMS: Improving 3D Object Detection with Fuzzy Classification in NMS

Non-maximum suppression (NMS) is an essential post-processing module used in many 3D object detection frameworks to remove overlapping candidate bounding boxes. However, an overreliance on classification scores and difficulties in determining appropriate thresholds can affect the resulting accuracy directly. To address these issues, we introduce fuzzy learning into NMS and propose a novel generalized Fuzzy-NMS module to achieve finer candidate bounding box filtering. The proposed Fuzzy-NMS module combines the volume and clustering density of candidate bounding boxes, refining them with a fuzzy classification method and optimizing the appropriate suppression thresholds to reduce uncertainty in the NMS process. Adequate validation experiments are conducted using the mainstream KITTI and large-scale Waymo 3D object detection benchmarks. The results of these tests demonstrate the proposed Fuzzy-NMS module can improve the accuracy of numerous recently NMS-based detectors significantly, including PointPillars, PV-RCNN, and IA-SSD, etc. This effect is particularly evident for small objects such as pedestrians and bicycles. As a plug-and-play module, Fuzzy-NMS does not need to be retrained and produces no obvious increases in inference time