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Intrahepatic cholangiocarcinoma (ICC) accounts for approximately 15% of primary liver cancers, and the incidence rate has been increasing in recent years. Surgical resection is the best treatment for ICC, but the 5-year survival rate is less than 30%. ICC signature genes are crucial for the early diagnosis of ICC, so it is especially important to identify signature genes. The aim of this study is to screen the signature genes of ICC and find the potential target for the treatment of ICC. We find that UBA3 is highly expressed in ICC, and knockdown of UBA3 inhibits ICC proliferation, invasion and migration. Mechanistic experiments show that UBA3 promotes ICC proliferation, invasion and migration by affecting ANXA2 through the MAPK signaling pathway. UBA3 is a target of bufalin, and bufalin targeting UBA3 inhibits ICC development and progression through the MAPK signaling pathway. In conclusion, our study shows that bufalin inhibits ICC by targeting UBA3, which has emerged as a new biomarker and potential therapeutic target for ICC.

Abstract Background Breast cancer (BC) patients tend to suffer from distant metastasis, especially bone metastasis. Methods All the analysis based on open-accessed data was performed in R software, dependent on multiple algorithms and packages. The RNA levels of specific genes were detected using quantitative Real-time PCR as a method of detecting the RNA levels. To assess the ability of BC cells to proliferate, we utilized the CCK8 test, colony formation, and the 5-Ethynyl-20-deoxyuridine assay. BC cells were evaluated for invasion and migration by using Transwell assays and wound healing assays. Results In our study, we identified the molecules involved in BC bone metastasis based on the data from multiple BC cohorts. Then, we comprehensively investigated the effect pattern and underlying biological role of these molecules. We found that in the identified molecules, the EMP1, ACKR3, ITGA10, MMP13, COL11A1, and THY1 were significantly correlated with patient prognosis and mainly expressed in CAFs. Therefore, we explored the CAFs in the BC microenvironment. Results showed that CAFs could activate multiple carcinogenic pathways and most of these pathways play an important role in cancer metastasis. Meanwhile, we noticed the interaction between CAFs and malignant, endothelial, and M2 macrophage cells. Moreover, we found that CAFs could induce the remodeling of the BC microenvironment and promote the malignant behavior of BC cells. Then, we identified MMP13 for further analysis. It was found that MMP13 can enhance the malignant phenotype of BC cells. Meanwhile, biological enrichment and immune infiltration analysis were conducted to present the effect pattern of MMP13 in BC. Conclusions Our result can improve the understanding of researchers on the underlying mechanisms of BC bone metastasis.

The new generation of pavement technology with the goal of longevity is an important supporting technology that can promote the achievement of sustainable development of high-speed roadways. To further investigate the evolution trend of long-life pavement performance, this paper paved experimental sections to explore the correlations between pavement structure combinations and pavement performances. This paper presented four experimental sections with different pavement structures, asphalt concrete layer thicknesses, and pavement materials. Then, this paper analyzed the effects of the seasonal factors, pavement structure, and lanes on the deflection value and rut depth from three dimensions by the Pearson correlation coefficient (PCC). Finally, this paper used the analysis of variance (ANOVA) to analyze the relationships between the layer thickness of various materials in the pavement structure and the pavement performances, including the deflection value, international roughness index (IRI), texture depth (TD), British Pendulum Number (BPN), sideway force coefficient (SFC), rut depth, and disease area. The results showed that the seasonal factors significantly affected the deflection values of pavement structures with PCCs of 0.61, 0.72, 0.53, and 0.78. The high temperatures increased the average deflection values by 22.85%, 72.88%, 77.61%, and 88.13%, respectively. Under the influence of high temperature in summer and traffic loads, the increased ranges of average rut depth were −0.2%, 4.89%, 9.56%, and 7.31%, respectively. The results of ANOVA showed that the pavement structure type and thickness of each structural layer significantly affected the deflection value, and there also was a strong correlation between the pavement structure type, thickness, BPN, and SFC with p-values less than 0.05. Increasing the thickness of the asphalt surface was beneficial for reducing the area of defects, while laying the semi-rigid base layer was beneficial for maintaining the deflection value and rut depth at a lower level.

The decline in mangrove ecosystems is a major contributor to the loss of biodiversity, extra carbon release, and local economic instability, particularly in tropical coastal regions that are constantly influenced by climate changes. Despite the importance of the mangroves, there is limited research investigating the consequences. Under the context, this research examines the correlation between mangrove density, sea level rise, and economic impacts in Southern Florida. The work aims to address three main questions: (i) what are the ecological impacts of sea level rising on mangroves density; (ii) what are the economic implications of mangrove loss; (iii) what extent of government intervention should be imposed on the environmental problem. The research presents a two-variable graph that examines the relationship between mangrove density in Southern Florida and sea level rise, analyzing its overall correlation in the Caribbean region. Another correlation study of the impacts of mangrove loss on local tourism is created and set as the focus. The conventional hedonic method is applied as the tool of evaluating mangroves value. The results demonstrate a close negative correlation between sea level and mangrove density, and a positive correlation of mangroves density and local tourism.

Scutellaria Radix, a traditional Chinese medicine, studies on its main active ingredient are limited. In this study, the purpose was to investigate the quality difference of Scutellariae Radix from different origins based on chemical components and biological activities. The chromatographic fingerprints of Scutellariae Radix from 33 origins were established using HPLC, and the antibacterial activities were studied with the microdilution method. Moreover, orthogonal partial least-square regression, pearson correlational analysis and grey relational analysis methods were performed to explore the relationship between the compositions and bioactivities. In addition, and origin identification model was established to comprehensively evaluate the quality of Scutellariae Radix. The results showed that Scutellariae Radix had in-vitro antibacterial effect on Staphylococcus aureus, and the best were in Gansu, Shandong Province. Multivariate statistical analysis common showed that three components were positively correlated with antibacterial activity, which were respectively wogonin, baicalein and oroxylin. In conclusion, the quality of Scutellariae Radix varies greatly from different origins, and the better was in Gansu and Shandong Province. This work successfully provides a general model that combined the chromatographic fingerprint and bioactivity assay to study the spectrum–effect relationships, which could be used to discover the primary active ingredients in traditional Chinese medicines.

This study was performed in Lhasa River Watershed to explore the contents of heavy metals in river water and assess the health risks. The test results show that the contents of arsenic (As), chromium (Cr) and uranium (U) are relatively low, reaching the Class III of the "Environmental quality standards for surface water (GB3838-2002)". Health risk assessment demonstrates that the average total risk value is 1.79×10-5 yr-1, which is lower than the maximum acceptable level of 5.05×10-5 yr-1 recommended by USEPA. Moreover, the average value of radionuclide risk (U) is calculated to be 9.47×10-9 yr-1, which is five orders of magnitude lower than the standard value of 5.0×10-4 yr-1. Therefore, the river water in the study area causes no significant health risk to people.

Abstract Background Our previous work found that mouse embryos could invade malignant cancer cells. In the process of implantation, embryo trophoblast cells express matrix metalloproteinases and the invasive ability of trophoblast cells is proportional to matrix metalloproteinase-9 protein expression. So the purpose of this study is to observe the effects of mouse embryos on human ovarian cancer cells in the co-culture environment in vitro and explore the possible mechanism of matrix metalloproteinase-9. Methods Several groups of human ovarian cancer cells HO8910PM were co-cultured with mouse embryos for different time duration, after which the effects of mouse embryos on morphology and growth behavior of HO8910PM were observed under the light microscope real-time or by H.E staining. Apoptosis was detected under laser confocal microscope by Annexin V-EGFP/PI staining in situ. Invasion ability of tumor cells was studied by transwell experiments. After matrix metalloproteinase 9 (MMP −9) activity was inhibited by MMP-9 Inhibitor I, the interaction between mouse embryos and human ovarian cancer cells HO8910PM was observed. Results Mouse embryos were able to invade co-cultured human ovarian cancer cell layer which extended in the bottom of the culture dish, and gradually pushed away tumor cells to form their own growth space. The number of apoptosis tumor cells surrounding the embryo increased under laser confocal microscope. After co-cultured with mouse embryos, tumor cells invasive ability was lowered compared with the control group. After MMP-9 activity was inhibited, the interaction between mouse embryos and HO8910PM cells had no significant difference compared with the normal MMP-9 activity group. Conclusion Mouse embryos were able to invade human ovarian cancer cells in vitro and form their own growth space, promote apoptosis of human ovarian cancer cells and lower their invasive ability. The mouse embryo was still able to invade human ovarian cancer cells after MMP-9 activity was inhibited.