Background Cancer development is strictly correlated to composition and physical properties of the extracellular matrix. Particularly, a higher matrix stiffness has been demonstrated to promote tumor sustained growth. Our purpose was to explore the role of matrix stiffness in liver cancer development. Methods The matrix stiffness of tumor tissues was determined by atomic force microscopy (AFM) analysis. In vitro, we used a tunable Polyacrylamide (PA) hydrogels culture system for liver cancer cells culture. The expression level of integrin β1, phosphorylated FAK, ERK1/2, and NF-κB in SMMC-7721 cells was measured by western blotting analysis. We performed MTT, colony formation and transwell assay to examine the tumorigenic and metastatic potential of SMMC-7721 cells cultured on the tunable PA hydrogels. SMMC-7721 cancer xenografts were established to explore the anticancer effects of integrin inhibitors. Results Our study provided evidence that liver tumor tissues from metastatic patients possessed a higher matrix stiffness, when compared to the non-metastatic group. Liver cancer cells cultured on high stiffness PA hydrogels displayed enhanced tumorigenic potential and migrative properties. Mechanistically, activation of integrin β1/FAK/ ERK1/2/NF-κB signaling pathway was observed in SMMC-7721 cells cultured on high stiffness PA hydrogels. Inhibition of ERK1/2, FAK, and NF-κB signaling suppressed the pro-tumor effects induced by matrix stiffness. Combination of chemotherapy and integrin β1 inhibitor suppressed the tumor growth and prolonged survival time in hepatocellular cancer xenografts. Conclusion A higher matrix stiffness equipped tumor cells with enhanced stemness and proliferative characteristics, which was dependent on the activation of integrin β1/FAK/ERK1/2/NF-κB signaling pathway. Blockade of integrin signals efficiently improved the outcome of chemotherapy, which described an innovative approach for liver cancer treatment.
Ecological adaptation of heavy metal polluted environments is significantly enhanced through plants inoculated with plant growth-promoting bacteria (PGPB), and the cost of phytostabilization in metal tailings can be reduced. On the basis of the systematic investigation of manganese tolerant plants which grew on Xiangtan manganese tailings, rhizosphere soils of the Chenopodium album Linn. were collected. One yellow manganese-resistant strain named XZL01 was isolated from the rhizosphere of fresh plants through concentration gradient screening technique, and the cellular form, physiological and biochemical tests were conducted, demonstrated as the growth curve and effects of temperature, pH, NaCl concentration on growth of the strain. All the results showed that 1) the strain reached logarithmic phase in 10-12h; 2) the optimal temperature range for growth of the strain was 25 ºC-30 ºC; 3) the optimal pH range for growth of the strain was 7.0-7.3; 4) the optimal NaCl concentration range for growth of the strain was 10g/L. In this study, the strain XZL01 was identified, and status of the strain in the taxonomy and phylogeny has been conformed according to 16S rDNA sequences, with the strain identificated as Microbacterium.sp XZL01.
A reverse blocking insulated gate bipolar transistor (IGBT) with partially narrow mesa (PNM) structure and trench collectors is proposed. An n-type carrier stored (n-cs) layer is introduced between two trench gates with the bulgy bottom, forming the PNM structure, which nicely shields high electric field from the n-cs layer at the forward blocking state. Hence, a highly doped n-cs layer can be used to enhance the carrier storage effect in the n-drift region at on-state to reduce the on-state voltage [V CE(sat) ]. Besides, an n-buffer layer is introduced between two trench collectors at the back side, acting as a field-stop (FS) layer at forwarding blocking state. At the reverse blocking state, the trench collectors shield high electric field from the n-buffer region and the n-cs layer acts as an FS layer, which ensures a high reverse breakdown voltage. Numerical simulation results show that the 1.4 kV proposed reverse blocking-IGBT can use a 38% thinner n-drift region and obtain a 45% lower V CE(sat) than the conventional counterpart.
This paper aims for the language-based product image retrieval task. The majority of previous works have made significant progress by designing network structure, similarity measurement, and loss function. However, they typically perform vision-text matching at certain granularity regardless of the intrinsic multiple granularities of images. In this paper, we focus on the cross-modal similarity measurement, and propose a novel Hierarchical Similarity Learning (HSL) network. HSL first learns multi-level representations of input data by stacked encoders, and object-granularity similarity and imagegranularity similarity are computed at each level. All the similarities are combined as the final hierarchical cross-modal similarity. Experiments on a large-scale product retrieval dataset demonstrate the effectiveness of our proposed method. Code and data are available at https://github.com/liufh1/hsl.
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