• Molecules and Cells
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• 제43권6호
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• pp.517-529
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• 2020

Carboxyl-terminal binding proteins (CtBPs) are transcription regulators that control gene expression in multiple cellular processes. Our recent findings indicated that overexpression of CtBP2 caused the repression of multiple bone development and differentiation genes, resulting in atrophic nonunion. Therefore, disrupting the CtBP2-associated transcriptional complex with small molecules may be an effective strategy to prevent nonunion. In the present study, we developed an in vitro screening system in yeast cells to identify small molecules capable of disrupting the CtBP2-p300 interaction. Herein, we focus our studies on revealing the in vitro and in vivo effects of a small molecule NSM00158, which showed the strongest inhibition of the CtBP2-p300 interaction in vitro. Our results indicated that NSM00158 could specifically disrupt CtBP2 function and cause the disassociation of the CtBP2-p300-Runx2 complex. The impairment of this complex led to failed binding of Runx2 to its downstream targets, causing their upregulation. Using a mouse fracture model, we evaluated the in vivo effect of NSM00158 on preventing nonunion. Consistent with the in vitro results, the NSM00158 treatment resulted in the upregulation of Runx2 downstream targets. Importantly, we found that the administration of NSM00158 could prevent the occurrence of nonunion. Our results suggest that NSM00158 represents a new potential compound to prevent the occurrence of nonunion by disrupting CtBP2 function and impairing the assembly of the CtBP2-p300-Runx2 transcriptional complex.

• Geomechanics and Engineering
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• 제25권1호
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• pp.59-73
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• 2021

There frequently exists inadequacy regarding the number of boreholes installed along tunnel alignment. While geophysical imaging techniques are available for pre-tunnelling geological characterization, they aim to detect specific object (e.g., water body and karst cave). There remains great motivation for the industry to develop a real-time identification technology relating complex geological conditions with the existing tunnelling parameters. This study explores the potential for the use of machine learning-based data driven approaches to identify the change in geology during tunnel excavation. Further, the feasibility for machine learning-based anomaly detection approaches to detect the development of clayey clogging is also assessed. The results of an application of the machine learning-based approaches to Xi'an Metro line 4 are presented in this paper where two tunnels buried in the water-rich sandy soils at depths of 12-14 m are excavated using a 6.288 m diameter EPB shield machine. A reasonable agreement with the measurements verifies their applicability towards widening the application horizon of machine learning-based approaches.

• Membrane and Water Treatment
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• 제5권1호
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• pp.1-14
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• 2014

A pilot-scale hybrid membrane bioreactor (HMBR) for real municipal wastewater treatment was developed by adding biofilm carriers into a conventional membrane bioreactor, distribution and dynamic changes of the extracellular polymeric substances (EPS) and their roles in membrane fouling were investigated. The results showed that the concentrations of loosely bond EPS (LB-EPS) and tightly bond EPS (TB-EPS) in activated sludge, carrier biofilm and sludge cake layer have been increased significantly with the running time of HMBR, during operation of the HMBR, EPS demonstrated positive correlations with membrane fouling. Compared to TB-EPS, LB-EPS showed more significant correlations with sludge physical properties and specific resistance to filtration (SRF) in HMBR, and thus demonstrated that LP-EPS have a stronger potential of fouling than TB-EPS. It was also found that a lower organic loading in HMBR could result a significant increase in EPS concentration, which would in turn influence membrane fouling in HMBR. This critical investigation would contribute towards a better understanding of the behavior, composition and fouling potential of EPS in HMBR operation.

• Nuclear Engineering and Technology
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• 제55권5호
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• pp.1763-1774
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• 2023

In this study, a series of flexible neutron/gamma shielding composites are fabricated through the doping of Gd₂O₃ into the matrix of SEBS with (M_Gd2O3: M_SEBS) % from 5% to 100%. Neutron transmittance test shows an exponential attenuation with the increase of areal density of Gd, in which the transmittance T ranges from 59.1440% to 35.3026%, with standard deviation less than 2.2743%, mass attenuation coefficient 𝜇_m from 0.3194 cm²/g to 0.4999 cm²/g, and half value layer-HVL value from 2.4530 mm to 1.1313 mm. Shielding efficiency of the Gd₂O₃/SEBS composites is basically improved in comparison with that of B₄C/SEBS. The transmittance T, mass/linear attenuation coefficient 𝜇_m and 𝜇, HVL and effective atomic number Z_eff for the shielding of γ rays (39 keV, 59 keV and 122 keV) are measured and calculated with XCOM as well as MCX programs. Finally, plots of the three dimensional relationships between transmittance, doping amount and thickness are provided to the guidance for engineering shielding design. In summary, the Gd₂O₃/SEBS composite is proved to be an effective flexible neutron/low energy γ rays shielding material, which could be of potential applications in the field of nuclear technology and nuclear engineering.

• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10911-10916
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• 2015

Background: Tumor metastases are the main reasons for oncotherapy failure. Paris polyphylla (Chinese name: Chonglou) has traditionally been used for its anti-cancer actions. In this article, we focus on the regulation of human lung cancer A549 cell metastases and invasion by Paris polyphylla steroidal saponins (PPSS). Materials and Methods: Cell viability was evaluated in A549 cells by MTT assay. Effects of PPSS on invasion and migration were investigated by wound-healing and matrigel invasion chamber assays. Adhesion to type IV collagen and laminin was evaluated by MTT assay. Expression and protease activity of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blotting and gelatin zymography, respectively. Results: PPSS exerted growth inhibitory effects on A549 cells, and effectively inhibited A549 cell adhesion, migration and invasion in a concentration-dependent manner. Western blotting and gelatin zymography analysis revealed that PPSS inhibited the expression and secretion of MMP-2 and MMP-9 in A549 cells. Conclusions: PPSS has the potential to suppress the migration, adhesion and invasion of A549 cells. PPSS could be a potential candidate for interventions against lung cancer metastases.

• International Journal of Stem Cells
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• 제16권3호
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• pp.315-325
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• 2023

Background and Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM. Methods and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP. Conclusions: Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.

• Structural Engineering and Mechanics
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• 제89권6호
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• pp.571-578
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• 2024

The bistable thin cylindrical shell is developable structure with the ability to transition between its two stable configurations. This structure offers significant potential applications due to its excellent deformability. In this paper, the composite thin cylindrical shell consisting of the composite layer and the piezoelectric layer was investigated. The material and geometric parameters of the shell were found to influence its stable characteristics. The analysis model of the composite thin cylindrical shell incorporating the piezoelectric layer was developed, and the expressions for its strain energy were derived. By applying the minimum energy principle, the impact of the electric field intensity on the bi-stable behaviors of the cylindrical shell was analyzed. The results showed that the shell exhibited the bistability only under the appropriate electric field strength. And the accuracy of the theoretical prediction was verified by simulation experiments. This study provides an important reference for the application of deployable structures.

• Journal of Power Electronics
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• 제14권2호
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• pp.203-216
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• 2014

In the conventional dc-dc converter, a pair of additional diode and the adjacent passive component capacitor/inductor can be added to the circuit with an X-shape connection, which generates a family of new topologies. The novel circuits, also called diode-assisted dc-dc converter, enhance the voltage boost/buck capability and have a great potential for high step-up/step-down power conversions. This paper mainly investigates and compares conventional dc-dc converter and diode-assisted dc-dc converter in wide range power conversion from the aspects of silicon devices, passive components requirements, electro-magnetic interference (EMI) and efficiency. Then, a comprehensive comparison example of a high step-up power conversion system was carried out. The two kinds of boost dc-dc converters operate under the same operation conditions. Mathematical analysis and experiment results verify that diode-assisted dc-dc converters are very promising for simultaneous high efficiency and high step-up/step-down power conversion in distributed power supply systems.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1105-1110
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• 2014

Objective: Metastases and invasion are the main reasons for oncotherapy failure. Momordica cochinchinensis (Mu Bie Zi in Chinese) had been used for a variety of purposes, and shown anti-cancer action. In this article, we focused on effects on regulation of breast cancer cell ZR-75-30 metastases and invasion by extracts of Momordica cochinchinensis seeds (ESMCs). Methods: Effect of ESMCs on ZR-75-30 human breast cancer cells proliferation were evaluated by MTT assay and on invasion and migration by wound-healing and matrigel invasion chamber assays. Expression and protease activity of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blotting and gelatin zymography, respectively. Results: ESMC revealed strong growth inhibitory effects on ZR-75-30 cells, and effectively inhibited ZR-75-30 cell invasion in a dose-dependent manner. Western blot and gelatin zymography analysis showed that ESMC significantly inhibited the expression and secretion of MMP-2 and MMP-9 in ZR-75-30 cells. Conclusions: ESMC has the potential to suppress the migration and invasion of ZR-75-30 cancer cells, and it might prove to of interest in the development of novel inhibitors for breast cancer.

• Structural Engineering and Mechanics
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• 제50권5호
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• pp.605-616
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• 2014

When the periodic cellular structure is loaded or swelling beyond the critical value, the structure may undergo a pattern transformation owing to the local elastic instabilities, thus leading to structural collapse and the structure changing to a new configuration. Based on this deformation-triggered pattern, we have proposed the novel composite gel materials. This designed material is a type of architectural material possessing special mechanical properties. In this study, the mechanical behavior of the composite gel periodic structure with various gel inclusions is studied further through numerical simulations. When pattern transformation occurs, it results in a different elastic relationship compared with the material at untransformed state. Based on the obtained nominal stress versus nominal strain behavior, the Poisson's ratio and corresponding deformed structure patterns, we investigate the performance of designed composite materials and the effects of the uniformly distributed gel inclusions on composite materials. A better understanding of the characteristics of these composite gel materials is a key to develop its potential applications on new soft machines.