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Abstract We took the silt soil in the Yellow River flood area of Zhengzhou City as the research object and carried out triaxial shear and triaxial creep tests on silt soil with different moisture contents (8%, 10%, 12%, 14%) to analyze the effect of moisture content on silt soil. In addition, the influence of moisture contents on soil creep characteristics and long-term strength was analyzed. Based on the fractional derivative theory, we established a fractional derivative model that can effectively describe the creep characteristics of silt soil in all stages, and used the Levenberg–Marquardt algorithm to inversely identify the relevant parameters of the fractional derivative creep model. The results show that the shear strengths of silt soil samples with moisture contents of 8%, 10%, 12% and 14% are 294 kPa, 236 kPa, 179 kPa and 161 kPa, respectively. The shear strength of silt soil decreases with increasing moisture content. When the moisture content increases, the cohesion of the silt soil decreases. Under the same deviatoric stress, the higher the moisture content of the silt soil, the greater the deformation will be. The long-term strength of silt soil decreases exponentially with the increase of moisture content. If the moisture content is 12%, the long-term strength loss rate of silt soil is the smallest, with a value of 32.96%. The calculated values of our creep model based on fractional derivatives have a high goodness of fit with the experimental results. This indicates that our model can better simulate the creep characteristics of silt soil. This study can provide a theoretical basis for engineering construction and geological disaster prevention in silt soil areas in the Yellow River flood area.

Soil caves collapse are typical geological hazards in karst areas. The disintegration of red clay is one of the important mechanisms leading to soil caves collapse. The pH of the soil pore solution has changed due to acid rains and the overuse of fertilizers. This study conducted disintegration tests to observe the disintegration rate of red clay in solutions with different pH values by a self-made disintegration apparatus. The inductively coupled plasma mass spectrometer (ICP-MS) and Zeta potential analyzer were used to test the cations concentration in the solutions and the electric potential (ζ potential) of red clay, analyzing the effect of pH on the physicochemical properties and the disintegration rate of red clay, providing a scientific basis for evaluating and preventing soil caves collapse. The results show that the disintegration rate in solutions with different pH values follows the order of pH = 11 > pH = 9 > pH = 3 > pH = 5 > pH = 7. When pH < 7, the cations concentration and the cations charges density in the soil solutions increased as the pH decreases. The electric potential changed from negative to positive as the pH decreases, with the potential value first decreasing and then increasing. When pH > 7, the cations concentration, cations charges density in the soil solutions, and the electric potential increased with the pH increased. The ratio of charges density to electric potential increased under both acidic and alkaline conditions, the thickness of the clay diffusion layer decreased, short-range gravitational decayed and repulsion increased, ultimately leading to the disintegration of red clay.

The effects of dietary emodin supplementation on the growth, gut health, and gut microbiota of common carp (Cyprinus carpio) were evaluated in this study. The basal diet (CONTROL group) was supplemented with 5 g/kg (EMODIN 5 group), 10 g/kg (EMODIN 10 group) and 20 g/kg (EMODIN 20 group) emodin for 6 weeks. Compared with the CONTROL alone group, the EMODIN 10 and EMODIN 20 groups of common carp had a significantly increased weight gain rate (WG%), specific growth rate (SGR%), and condition factor ratio (CF%) and decreased feed conversion ratio (FCR). The activities of intestinal digestive enzymes, including α-amylase (AMS), protease (PRT) and lipase (LPS), were also significantly increased in the emodin group (EMODIN 10 and EMODIN 20). Emodin also enhanced intestinal barrier function by increasing the length of intestinal villi, the number of goblet cells, and expression of the occludin gene. The dominant gut probiotics Cetobacterium and Actinobacteriota_unclassified were significantly enriched in the emodin group, while Aeromonas abundance was depleted, indicating that the intestinal barrier health of the emodin-treated carp improved. We also observed elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), catalase (CAT) and superoxide dismutase (T-SOD) activities, and malondialdehyde (MDA) levels were reduced in the serum of the treatment group, which means that the fish's immunity was improved. There was functional enrichment of gut microbiota immune system pathways in the emodin group, which highlights the importance of gut immunity. Network pharmacology analysis showed that the NF-κB signaling pathway was significantly enriched in the intestine-immunity axis. Accordingly, RTPCR showed that emodin affected the intestinal expression of NF-κB signaling pathway-related immune factors in artificially infected fish, including decreased NF-κB, IL-6 and TNF-α expression and increased TLR22 expression. Correlation analysis showed that downregulated NF-κB expression upon emodin addition (EMODIN 20) was related to increased Cetobacterium abundance. Therefore, dietary emodin supplementation may enhance intestinal immune defense by regulating the intestinal microbiota, which promotes common carp growth.

Abstract Oxidative stress, as a characteristic of cellular aerobic metabolism, plays a crucial regulatory role in the development and metastasis of gastric cancer (GC). Long noncoding RNAs (lncRNAs) are important regulators in GC development. However, research on the prognostic patterns of oxidative stress-related lncRNAs (OSRLs) and their functions in the immune microenvironment is currently insufficient. We identified the OSRLs signature (DIP2A-IT1, DUXAP8, TP53TG1, SNHG5, AC091057.1, AL355001.1, ARRDC1-AS1, and COLCA1) from 185 oxidative stress-related genes in The Cancer Genome Atlas (TCGA) cohort via random survival forest and Cox analyses, and the results were subsequently validated in the Gene Expression Omnibus (GEO) dataset. The patients were divided into high- and low-risk groups by the risk score of the OSRLs signature. Longer overall survival was detected in the low-risk group than in the high-risk group in both the TCGA cohort (P 1, P = 0.005), and time-dependent receiver operating characteristic (ROC) curve analysis and nomogram analysis were utilized to evaluate the predictive ability of the risk model. Next, gene set enrichment analysis revealed that the immune-related pathway, Wnt/ $$\upbeta$$ β -catenin signature, mammalian target of rapamycin complex 1 signature, and cytokine‒cytokine receptor interaction was enriched. High-risk patients were more responsive to CD200, TNFSF4, TNFSF9, and BTNL2 immune checkpoint blockade. The results of qRT‒PCR further proved the accuracy of our bioinformatic analysis. Overall, our study identified a novel OSRLs signature that can serve as a promising biomarker and prognostic indicator, which provides a personalized predictive approach for patient prognosis evaluation and treatment.

Guilin is a famous karst area, and currently the view that the disintegration of red clay will cause soil cave collapse is increasingly recognized. In order to study the influence of the coupling effect of moisture content and void ratio on the disintegration of red clay, different moisture contents and void ratios of Guilin red clay were placed on a self-made disintegration apparatus to record the real-time disintegration amount and observe the disintegration phenomenon. Images of the structural characteristics of soil were obtained by a scanning electron microscope (SEM). Additionally, nuclear magnetic resonance (NMR) was applied to analyze the distribution of water in both natural and saturated states. The results show that the disintegration rate of red clay decreases as the initial moisture content increases, but increases with the increase of void ratio. Both moisture content and void ratio affect the structural characteristics of red clay. When the moisture content remains constant, the soil changes from a three-peak to a two-peak structure as the void ratio increases. The total area and secondary peak area of the T2 spectrum increase, while the starting T2 value of the main peak shifts to the right and the area decreases. Meanwhile, the starting T2 value of the secondary peak shifts to the right and the area increases. When the void ratio remains constant, the starting T2 value of the main peak gradually shifts to the left and the area decreases as the moisture content increases. However, the starting T2 value of the secondary peak shifts to the right and the area decreases or first decreases and then increases. The disintegration rate does not exhibit a significant relationship with either pore volume or macropore volume. The combined water saturation shows a bilinear relationship with both the moisture content and void ratio, where it increases as the initial moisture content increases, but decreases as the void ratio increases, with a correlation coefficient of 0.9929. The disintegration rate has an exponential relationship with the combined water saturation, and it decreases as the combined water saturation increases, with a correlation coefficient of 0.9934.

In order to explore the creep characteristics of red clay under different pressures, the stress–strain curve and stress–strain–time curve of red clay under different pressures were obtained, and the triaxial shear and creep characteristics of red clay under different pressures were analysed. A triaxial shear test and creep test were carried out on red clay from Guilin as the research object under different pressures. The results show that: ➀ the cohesion and the angle of internal friction of red clay from Guilin, obtained from a triaxial shear test, are 57.20 kPa and 22.47°, respectively; ➁ according to the physical meaning of the parameters of the Burgers creep model, a simple and practical parameter inversion method is proposed, which can be used to obtain the parameters of the Burgers model for red clay under different perimeter pressures and differing deviatoric stress; and ➂ when comparing the calculation results with the test results, the correlation coefficients R2 of the two are above 0.9, with a good fitting effect, so the model can accurately describe the creep characteristics of red clay from Guilin. This study can provide a theoretical basis and technical support for engineering construction in the red clay area of Guilin.

To understand the performance of ecological pervious concrete prepared with mixed sandstone/limestone aggregates, limestone and sandstone were used as two aggregates. The sandstone-to-limestone volume ratio was calculated in 0 : 1, 0.25 : 0.75, 0.5 : 0.5, 0.75 : 0.25, and 1 : 0 in coarse aggregate to prepare ecological pervious concrete specimens. The compressive test, water permeability test, cooling test, evaporation test, alkaline test, and scanning electron microscope (SEM) tests were carried out with qualified compressive strength as the indicator to determine the optimum sandstone-to-limestone volume ratio for the ecological pervious concrete. The results show that the water permeability, cooling property, and evaporation property of the ecological pervious concrete increase with the sandstone content. When the sandstone-to-limestone volume ratio is less than 0.32 : 0.68 (the substitution rate of sandstone for limestone in ecological pervious concrete is 32%), the strength of ecological pervious concrete meets the requirements of 5 MPa and achieves the best permeability coefficient of 9 mm/s. This realizes the full use of net water storage and cooling capacity of the ecological pervious concrete and makes the ecological pervious concrete meet the construction requirement of slope protection in sponge cities in the south.

To explore the effect and applicability of contour reverse slope terraces in water and soil conservation of karstic red clay soil area in northern Guangxi, rainfall simulation experiments were conducted on bare red clay soil slopes laid with contour reverse slope terraces to find the erosion pattern in response to different rainfall intensities (15, 30, and 50 mm/h) and bedrock porosities (1%, 3%, and 5%). The results showed that contour reverse slope terraces can change the spatial distribution of surface runoff, divert surface runoff to the underground, and increase underground sediment yielding. It is found that contour reverse slope terraces can effectively reduce surface soil erosion though it still remains dominant erosion for red clay terraced farmland, with surface runoff reduced by 71%, 52%, and 46% and surface sediment loss reduced by 70%, 65%, and 63%, respectively, when the rainfall intensity is set at 15 mm/h, 30 mm/h, and 50 mm/h. It is concluded that contour reverse slope terraces can help reduce water and soil erosion of red clay terraced farmland in northern Guangxi.

As a prominent component of the construction field of sponge cities, ecological concrete is an essential tool to reach the goals of green, low-carbon living and sustainable development. A quantitative summary of the preliminary research on ecological concrete infrastructure in sponge city architecture is needed. Therefore, CiteSpace and VOSviewer were applied to perform a comparative analysis of the number of papers, countries, institutions, core authors, literature co-citations, research hotspots, and future trends in ecological concrete in the sponge city construction industry. The results show that the number of papers on ecological concrete is increasing, the research collaboration between domestic and foreign authors is relatively single, and there is insufficient interdisciplinary integration between institutions and the phenomenon of “relatively independent research.” The number of papers published in the field of ecological concrete construction has been on the rise, reaching more than 100 in each of the last 10 years, with China and the United States contributing more to the scientific output of the field. To meet the needs of global environmental protection and resource conservation, the theme of “promoting comprehensive resource conservation and recycling” will continue in the future, making concrete a feature of green, low-carbon, sustainable development and other areas of environmental protection in the construction field.

Abstract The hepatic stellate cells (HSCs) activation by myofibroblastic differentiation is critical for liver fibrosis. Crosstalk between stromal cells and tumor cells in the microenvironment alters the properties and facilitates the growth and metastasis of tumor cells. How mechanical stimuli originally stiffness of extracellular matrix (ECM) contribute to tumor development remains poorly understood. Here, we demonstrated that stiffness contributes to mechanosignal transduction in HSCs, which promotes hepatocellular carcinoma (HCC) cells growth and metastasis through secretion of FGF2. On stiffness matrix, HSCs activation was confirmed by immunofluorescence (IF) and Western blot (WB) for α-smooth muscle actin (SMA). Increasing matrix stiffness promoted HSCs activation by CD36-AKT-E2F3 mechanosignaling through shRNA-mediated E2F3 knockdown, AKT inhibitors, and CD36 shRNA. Moreover, ChIP-qPCR. Confirmed that E2F3 combined the promoter of FGF2, and stiffness promoted FGF2 expression. On a stiff matrix, HCC cells cultured with conditioned media (CM) from HSCs increased HCC cells growth and metastasis by binding FGFR1 to activate PI3K/AKT and MEK/ERK signaling pathways. Moreover, conditional E2F3 knockout mice were subjected to CCl4 treatment to assess the role of E2F3 in HSC activation. Additionally, the DEN-induced HCC model was also used to evaluate the role of E2F3 in liver fibrosis and HCC growth. In conclusion, we demonstrated that stiffness-induced HSC activation by E2F3 dependent. Stiffness activated CD36-AKT-E2F3 signaling and targeted FGF2 transcription, subsequently, activated HCC growth and metastasis by FGFR1-mediated PI3K/AKT and MEK/ERK signaling.

The unconfined compressive strength of specimens with three moisture contents and three NaOH/TMG ratios (sodium hydroxide mass/solid mass, where solid contains tungsten tailings, metakaolin and commercial geopolymer) cured at 60–100 ℃ for seven days was conducted to investigate the temperature effect and action mechanism of tungsten tailings strength activated by NaOH. The test results of the scanning electron microscope (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were adopted to analyze the micro characteristics of the mixture under different curing temperatures. The test results indicate that the unconfined compressive strength of tungsten tailings activated by NaOH increases first and then decreases with the increase of curing temperature, and reaches the maximum at 90 ℃. C(N)-A-S-H gels mixed with poly-sialate (PS) and poly-sialate-siloxo (PSS) types are generated at different proportions at different temperatures activated by NaOH. The relative content of PS type gels increases when the curing temperature rises from 60 ℃ to 90 ℃, and decreases when the temperature continues to rise to 100 ℃. The greater the total amount of gel and the relative content of PS-type gel, the greater the strength of the specimens. In this study, the unconfined compressive strength is strongest in the temperature of 90 ℃. It was the optimal curing temperature. The minimum and the maximum strengths were 12.4 MPa and 42.8 MPa when the curing temperature is over or equal to 70 ℃, which meets the strength requirements of building bricks of MU10. In conclusion, the research results provide scientific basis and references for the resource utilization of tungsten tailings.

In engineering practice, properly characterizing the spatial distribution of soil liquefaction potential and induced surface settlement is essential for seismic hazard assessment and mitigation. However, geotechnical site investigations (e.g., cone penetration test (CPT)) usually provide limited and sparse data with high accuracy. Geophysical surveys provide abundant two-dimensional (2D) data, yet their accuracy is lower than that of geotechnical investigations. Moreover, correlating geotechnical and geophysical data can effectively reduce site investigation costs. This study proposes a data-driven adaptive fusion sampling strategy that automatically develops an assessment model of the spatial distribution of soil liquefaction potential from spatially sparse geotechnical data, performs monitoring of liquefaction-induced settlement, and integrates spatiotemporally unconstrained geophysical data to update the model systematically and quantitatively. The proposed strategy is illustrated using real data, and the results indicate that the proposed strategy overcomes the difficulty of generating high-resolution spatial distributions of liquefaction potential from sparse geotechnical data, enables more accurate judgment of settlement variations in local areas, and is an effective tool for site liquefaction hazard analysis.

The undrained shear strength of clay is an important index for the calculation of the bearing capacity of the foundation soil, the calculation of the soil pressure of the foundation pit, and the analysis of the slope stability. Therefore, the purpose of this paper is to conduct a comprehensive study of the combined use of machine learning with clay theoretical equations to estimate it. Under the Bayesian framework, the CatBoost algorithm (CatBoost–Bayesian) based on Bayesian optimization algorithm was developed to obtain the feature importance level of soil parameters affecting the undrained shear strength of clay, so as to adaptively couple the theoretical equation of undrained shear strength of K0 consolidated clay, which was derived from the modified Cambridge model. Then, the theoretical equation of undrained shear strength of the isotropically consolidated clay was established from the critical state of the clay parameters. Finally, it was illustrated and verified using the experimental samples of Finnish clay. The results indicate that the theoretical equation established by the overconsolidation ratio and effective overburden pressure parameters can well estimate the undrained shear strength of isotropically consolidated clays, and the parameter uncertainty can be considered explicitly and rigorously.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-018-0717-3

Local and systemic metastasis of hepatocellular carcinoma (HCC) causes the poor prognosis and increasing evidence confirms that aberrant miRNAs were involved in cancer progression. However, the expression and mechanisms of a specific miR-3194-3p in HCC remains unknown. In this research, we demonstrated that miR-3194-3p, significantly down-regulated in HCC tissues and cell lines, was associated with metastasis and recurrence of HCC. Notably, gain- and loss-of-function assays demonstrated that miR-3194-3p inhibited the migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells in vitro and in vivo. BCL9, up-regulated in HCC tissues, was a direct downstream target of miR-3194-3p and mediated the functional influence of miR-3194-3p. Most importantly, miR-3194-3p exerted its function by regulating β-catenin pathway. Moreover, miR-3194-3p and BCL9 expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the down-expression of miR-3194-3p in HCC. Also, the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by miR-3194-3p. Altogether, our study suggested that miR-3194-3p inhibits HCC EMT via decreasing Wnt/β-catenin signaling through targeting BCL9 and might be a therapeutic target for HCC.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-019-1188-x.

Abstract Background Accumulating evidence has highlighted the potential role of long non-coding RNAs (lncRNAs) in the biological behaviors of hepatocellular carcinoma (HCC). Here, we elucidated the function and possible molecular mechanisms of the effect of lncRNA-AGAP2-AS1 on the biological behaviors of HCC. Methods EdU, Transwell and flow cytometry were used to determine proliferation, migration, invasion and apoptosis of HCC cells in vitro. The subcutaneous tumor model and lung metastasis mouse model in nude mice was established to detect tumor growth and metastasis of HCC in vivo. The direct binding of miR-16-5p to 3’UTR of ANXA11 was confirmed by luciferase reporter assay. The expression of AGAP2-AS1 and miR-16-5p in HCC specimens and cell lines were detected by real-time PCR. The correlation among AGAP2-AS1 and miR-16-5p were disclosed by a dual-luciferase reporter assay, RIP assay and biotin pull-down assay. Results Here, we demonstrated that AGAP2-AS1 expression was up-regulated in HCC tissues and cell lines, especially in metastatic and recurrent cases. Gain- and loss-of-function experiments indicated that AGAP2-AS1 promoted cell proliferation, migration, invasion, EMT progression and inhibited apoptosis of HCC cells in vitro and in vivo. Further studies demonstrated that AGAP2-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-16-5p in HCC cells. Functionally, gain- and loss-of-function studies showed that miR-16-5p promoted HCC progression and alteration of miR-16-5p abolished the promotive effects of AGAP2-AS1 on HCC cells. Moreover, ANXA11 was identified as direct downstream targets of miR-16-5p in HCC cells, and mediated the functional effects of miR-16-5p and AGAP2-AS1 in HCC, resulting in AKT signaling activation. Clinically, AGAP2-AS1 and miR-16-5p expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the overexpression of AGAP2-AS1 in HCC. And the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by AGAP2-AS1 knockdown. Conclusions Taken together, this research supports the first evidence that AGAP2-AS1 plays an oncogenic role in HCC via AGAP2-AS1/miR-16-5p/ANXA11/AKT axis pathway and represents a promising therapeutic strategy for HCC patients.

Abstract Background Cancer stem cells (CSCs) require stromal signals for maintaining pluripotency and self-renewal capacities to confer tumor metastasis. Resolvin D1 (RvD1), an endogenous anti-inflammatory lipid mediator, has recently been identified to display anti-cancer effects by acting on stroma cells. Our previous study reveals that hepatic stellate cells (HSCs)-derived cartilage oligomeric matrix protein (COMP) contributes to hepatocellular carcinoma (HCC) progression. However, whether RvD1 inhibits paracrine of cancer-associated fibroblasts (CAFs)-derived COMP to prevent epithelial-mesenchymal transition (EMT) and cancer stemness in HCC remains to be elucidated. Methods CAFs were isolated from HCC tissues. Direct and indirect co-culture models were established to analyze the interactions between HCC cells and CAFs in the presence of RvD1 in vitro. The transwell and tumor sphere formation assays were used to determine invasion and stemness of HCC cells. The subcutaneous tumor formation and orthotopic liver tumor models were established by co-implantation of CAFs and HCC cells to evaluate the role of RvD1 in vivo. To characterize the mechanism of RvD1 inhibited paracrine of COMP in CAFs, various signaling molecules were analyzed by ELISA, western blotting, reactive oxygen species (ROS) detection, immunofluorescence staining, dual luciferase reporter assay and chromatin immunoprecipitation assay. Results Our data revealed that RvD1 treatment can impede the CAFs-induced cancer stem-like properties and the EMT of HCC cells under co-culture conditions. In vivo studies indicated that RvD1 intervention repressed the promoting effects of CAFs on tumor growth and metastasis of HCC. Furthermore, RvD1 inhibited CAF-induced EMT and stemness features of HCC cells by suppressing the secretion of COMP. Mechanistically, formyl peptide receptor 2 (FPR2) receptor mediated the suppressive effects of RvD1 on COMP and forkhead box M1 (FOXM1) expression in CAFs. Notably, RvD1 impaired CAF-derived COMP in a paracrine manner by targeting FPR2/ROS/FOXM1 signaling to ultimately abrogate FOXM1 recruitment to the COMP promoter. Conclusion Our results indicated that RvD1 impaired paracrine of CAFs-derived COMP by targeting FPR2/ROS/FOXM1 signaling to repress EMT and cancer stemness in HCC. Thus, RvD1 may be a potential agent to promote treatment outcomes in HCC.

Background: Aberrant expression of miR-532-3p was involved in progression and development of multiple cancers, whereas miR-532-3p has not been reported in hepatocellular carcinoma (HCC). The aim of this study was to elucidate the functions of miR-532-3p in progression of HCC. Methods: Real-time PCR in HCC tissues and cell lines and database analysis were conducted for detection of the expression of miR-532-3p in HCC. Then, the association of miR-532-3p with clinicopathological features and prognosis of HCC patients were statistically measured. Subsequently, we attempted to observe the effects of miR-532-3p on migration, invasion and proliferation of HCC cells by Wound healing assay, Transwell assays, MTT assay and EdU assay. Furthermore, bioinformatics tools, database analysis, luciferase reporter gene assay and rescue experiments were conducted to explore the target of miR-532-3p in HCC, and to explore whether the target mediated the effects of miR-532-3p on HCC cells. Results: Our findings and data from databases consistently indicated that the miR-532-3p expression level was higher in HCC. In addition, high miR-532-3p expression was found to be closely related to larger tumor size (P = 0.0027), presence of vascular invasion (P = 0.015), and advanced TNM stage (P = 0.015). In addition, experiments in vitro revealed that miR-532-3p promotes migration, invasion and proliferation of HCC cells. Furthermore, receptor protein tyrosine phosphatase T (PTPRT) was identified as the target and mediator of miR-532-3p in HCC cells. Conclusion: Our results demonstrate that miR-532-3p, which is frequently up-regulated in HCC, contributes to HCC cells mobility and proliferation through targeting PTPRT.

Abstract Background Cartilage oligomeric matrix protein (COMP) is known to promote fibrosis in skin, lung and liver. Emerging evidence shows that COMP plays critical roles in tumor development, including breast cancer, colon cancer and hepatocellular carcinoma (HCC). Nevertheless, the role of COMP in HCC proliferation and metastasis and its underlying mechanisms remain fully unclear. Methods Serum COMP was determined by ELISA. Cell Counting Kit-8 and plate colony formation were performed to evaluate cell proliferation. Wound healing and transwell assays were used to determine migration and invasion of HCC cells. Western blotting and immunofluorescence were carried out for detection of epithelial-to-mesenchymal transition (EMT) markers and MMPs in HCC cells. The in vivo role of COMP was evaluated using mouse models. We also measured effects of hepatic stellate cells (HSCs)-conditioned medium (CM) on HCC progression using transwell coculture system. Results Here, we found that serum COMP levels in HCC patients were significantly higher than those in healthy controls. Accordingly, high serum COMP levels in HCC patients significantly correlated with malignant clinical characteristics and poor clinical outcomes. Next, we investigated that recombinant human COMP protein (rCOMP) treatment resulted in increased abilities of proliferation, invasion and migration of HCC cells. Furthermore, rCOMP treatment enhanced proliferative and metastatic colonization of HCC cells in vivo. Mechanistically, CD36 receptor played an essential role in COMP-mediated HCC cell proliferation and metastasis. Functionally, COMP/CD36 signaling caused phosphorylation of ERK and AKT, resulting in the upregulation of tumor-progressive genes such as EMT markers, MMP-2/9, Slug and Twist in HCC cells. Interestingly, we revealed that COMP was secreted by HSCs. CM of LX2 cells with COMP knockdown showed weaker effects on the activation of MEK/ERK and PI3K/AKT signaling pathways in HCC cells compared to control CM. Conclusions Our findings indicated that HSCs-derived COMP collaborated with CD36 and subsequently played an essential role in MEK/ERK and PI3K/AKT-mediated HCC progression. COMP might act as a promising target for the diagnosis and treatment of aggressive HCC.

Abstract Background Accumulating evidence confirm that aberrant microRNAs (miRNAs) expression contributes to hepatocellular carcinoma (HCC) development and progression. Previous study reported that miR-1468 showed an up-regulated tendency and might be a potential prognostic biomarker in HCC samples derived from TCGA database. However, the role of miR-1468 and its underlying mechanisms involved in the growth and metastasis of HCC remain poorly investigated. Methods CCK-8, EdU, colony formation and flow cytometry were used to determine proliferation, cell cycle progression and apoptosis of HCC cells in vitro. The subcutaneous tumor model in nude mice was established to detect tumor growth of HCC in vivo. The direct binding of miR-1468 to 3’UTR of Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 2 (CITED2) and Up-frameshift protein 1 (UPF1) was confirmed by luciferase reporter assay. Results Here, we demonstrated that miR-1468 expression was up-regulated in HCC tissues and cell lines. Clinical analysis revealed that increased miR-1468 level was significantly correlated with malignant prognostic features and shorter survival. Gain- and loss-of-function experiments indicated that miR-1468 promoted cell proliferation, colony formation, cell cycle progression and induced apoptosis of HCC cells in vitro and in vivo. Moreover, CITED2 and UPF1 were identified as direct downstream targets of miR-1468 in HCC cells, and mediated the functional effects of miR-1468 in HCC, resulting in peroxisome proliferator-activated receptor-γ (PPAR-γ)/AKT signaling activation. In clinical samples of HCC, miR-1468 inversely correlated with the levels of CITED2 and UPF1, which were confirmed to be down-regulated in HCC. Restoration of CITED2 or UPF1 expression at least partially abolished the biological effects of miR-1468 on HCC cells. Moreover, alteration of PPAR-γ or AKT phosphorylation could reverse the function of miR-1468 in HCC. Conclusions Taken together, this research supports the first evidence that miR-1468 plays an oncogenic role in HCC via activating PPAR-γ/AKT pathway by targeting CITED2 and UPF1, and represents a promising therapeutic strategy for HCC patients.

Background/Aims: Hypoxic microenvironment, a common feature of hepatocellular carcinoma (HCC), can induce HIF-1α expression and promote the epithelial-mesenchymal transition (EMT) and invasion of cancer cells. However, the underlying molecular mechanisms have not fully elucidated. Methods: HCC cells were cultured under controlled hypoxia conditions or normoxic conditions. Transwell assays were used to examine the migration and invasion capacity. HIF-1α siRNA, cyclopamine (a SMO antagonist) and GLI1 siRNA were used to inhibit HIF-1α transcription or Hh signaling activation. Results: In present study, we first observed a strongly positive correlation between HIF-1α and GLI1 expression in HCC tissues. Then, we showed that hypoxia significantly promoted EMT process and invasion of HCC cells, associated with activating the non-canonical Hh pathway without affecting SHH and PTCH1 expression. HIF-1α knockdown mitigated hypoxia-induced SMO and GLI1 expression, EMT invasion of HCC cells. Moreover, the SMO inhibitor or GLI1 siRNA also reversed the hypoxia-driven EMT and invasion of HCC cells under hypoxia condition. Here, we show that non-canonical Hh signaling is required as an important role to switch on hypoxia-induced EMT and invasion in HCC cells. In addition, we found that hypoxia increased ROS production and that ROS inhibitors (NAC) blocked GLI1-dependent EMT process and invasion under hypoxic conditions. To determine a major route of ROS production, we tested whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is involved in hypoxia-induced ROS production. NOX4 expression was found to be increased at both mRNA and protein levels in hypoxic HCC cells. Furthermore, siRNA-mediated knockdown of NOX4 expression abolished hypoxia induced ROS generation and GLI1-dependent activation and invasion of HCC cells. Conclusion: Our findings indicate that hypoxia triggers ROS-mediated GLI1-dependent EMT progress and invasion of HCC cells through induction of NOX4 expression. Thus, hypoxia-driven ROS mediated non-canonical Hh signaling may play an important role in the initiation of EMT and provides a potential marker for cancer prevention and treatment.

Abstract Background Heat shock protein 90 (HSP90) functions as a well-known onco-protein to regulate protein conformation, stability and degradation. Pyruvate kinase M2 (PKM2), a critical regulator of the metabolism, growth and metastasis of cancer cells, has been confirmed to be overexpressed in various human cancer including hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the oncogenic functions of HSP90 and PKM2 overexpression in HCC remain unknown. Methods The expression of HSP90 and PKM2 in HCC specimens and cells were detected by immunoblotting and immunostaining. The interaction between HSP90 and PKM2 was confirmed by tandem affinity purification, co-immunoprecipitation and Glutathione S transferase (GST)-pulldown assay. Results In this study, we found that HSP90 could bind to PKM2 and subsequently increased PKM2 abundance in HCC cells. Immunohistochemistry (IHC) staining showed that HSP90 level was positively correlated with PKM2 level in HCC tissues. Mechanistically, HSP90 was found to increase the phosphorylation of PKM2 at Thr-328. Protein kinase glycogen synthase kinase-3β (GSK-3β) formed a protein complex with HSP90 and PKM2, and directly mediated Thr-328 phosphorylation of PKM2 induced by HSP90. Thr-328 phosphorylation was critical for maintaining PKM2 stability and its biological functions in regulating glycolysis, mitochondria respiration, proliferation and apoptosis. Functionally, we found that HSP90 promoted the glycolysis and proliferation and inhibited apoptosis of HCC cells in a PKM2 dependent manner. In vivo experiments disclosed that PKM2 was required for the promoting effects of HSP90 on the growth of HCC cells in mice. Furthermore, we demonstrated that positive expression of HSP90 and PKM2 was correlated with poor clinicopathological features including high alpha fetoprotein (AFP) level, large tumor size, portal vein tumor thrombus (PVTT) and advanced tumor-node-metastasis (TNM) stage. Furthermore, we demonstrated that positive expression of HSP90 and PKM2, and a combination of these proteins could strongly predict the poor prognosis of HCC patients. Conclusions We suggest that HSP90 potentiates the glycolysis and proliferation, reduces the apoptosis and thus enhances the growth of HCC cells through PKM2.

Abstract Background Recently, it has been reported that long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2), a novel tumor suppressor, participates in regulating the carcinogenesis and suppresses tumor progression by sponging microRNAs (miRNAs). However, the expression and function of CASC2 in hepatocellular carcinoma (HCC) remain unclear. Methods The expression of CASC2 and miR-367 in HCC specimens and cell lines were detected by real-time PCR. Western blotting and immunohistochemistry were carried out for detection of epithelial-to-mesenchymal transition (EMT) markers in HCC. Transwell assays were used to determine migration and invasion of HCC cells. A mouse model for lung metastasis was established to evaluated HCC metastasis in vivo. The correlation among CASC2, miR-367 and F-box and WD repeat domain containing 7 (FBXW7) were disclosed by a dual-luciferase reporter assay, RIP assay and biotin pull-down assay. Results Here, CASC2 expression was significantly downregulated in HCC tissues, especially in aggressive and recurrent cases. In accordance, CASC2 underexpression was observed in HCC cell lines compared to LO2. In vitro and in vivo experiments revealed that CASC2 inhibited migration and invasion of HCC cells. Additionally, CASC2 repressed EMT process of HCC cells. Further studies demonstrated that CASC2 could function as a competing endogenous RNA (ceRNA) by sponging miR-367 in HCC cells. Functionally, gain- and loss-of-function studies showed that miR-367 promoted migration, invasion and EMT progression of HCC cells. Moreover, further investigations disclosed that FBXW7 was a downstream target of miR-367 and CASC2 prohibited EMT progression and subsequently exerted its anti-metastatic effects via CASC2/miR-367/FBXW7 axis in HCC cells. Clinically, CASC2 underexpression and miR-367 overexpression were closely correlated with the metastasis-associated clinicopathologic features. Notably, CASC2 low-expressing and miR-367 high-expressing HCC patients showed the poorest clinical outcome. Conclusions Overall, we conclude that the CASC2/miR-367/FBXW7 axis may be a ponderable and promising therapeutic target for HCC.

Abstract Background Increasing evidences demonstrate that miRNAs contribute to development and progression of hepatocellular carcinoma (HCC). Underexpression of miR-1296 is recently reported to promote growth and metastasis of human cancers. However, the expression and role of miR-1296 in HCC remain unknown. Methods The levels of miR-1296 in HCC tissues and cells were detected by qRT-PCR. Immunoblotting and immunofluorescence were used for detection of epithelial-to-mesenchymal transition (EMT) progression in HCC cells. Transwell assays were performed to determine migration and invasion of HCC cells. A lung metastasis mouse model was used to evaluated metastasis of HCC in vivo. The putative targets of miR-1296 were disclosed by public databases and a dual-luciferase reporter assay. Results We found that the expression of miR-1296 was reduced in HCC tissues and cell lines, and it was associated with metastasis and recurrence of HCC. Notably, miR-1296 overexpression inhibited migration, invasion and EMT progress of HCCLM3 cells, while miR-1296 loss facilitated these biological behaviors of Hep3B cells in vitro and in vivo. In addition, miR-1296 inversely regulated SRPK1 abundance by directly binding to its 3′-UTR, which subsequently resulted in suppression of p-AKT. Either SRPK1 re-expression or PI3K/AKT pathway activation, at least partially, abolished the effects of miR-1296 on migration, invasion and EMT progress of HCC cells. Furthermore, miR-1296 and SRPK1 expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the underexpression of miR-1296 in HCC. And the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by miR-1296. Conclusions Underexpression of miR-1296 potentially serves as a prognostic biomarker in HCC. Hypoxia-induced miR-1296 loss promotes metastasis and EMT of HCC cells probably by targeting SRPK1/AKT pathway.

Lymphocyte‐specific protein 1 (LSP1) has been reported to regulate cell biology in several human cancers including lymphoma and breast cancer. However, the functions of LSP1 in human hepatocellular carcinoma (HCC) are still unknown. In this study, we found that LSP1 expression was downregulated in HCC tissues and cell lines, and lower LSP1 expression was correlated with poor clinicopathological features including large tumor size, high Edmondson–Steiner grading and advanced tumor–node–metastasis (TNM) stage. Additionally, we demonstrated that patients with high LSP1 expression had significantly better overall survival and disease‐free survival. Moreover, LSP1 was found to be an independent factor for predicting the prognosis of HCC patients. In vitro and in vivo assays showed that overexpressing LSP1 inhibited HCC growth by inducing both apoptosis and growth arrest. Mechanistically, we found that expression of phosphorylated extracellular regulated protein kinases 1 and 2 (ERK1/2) was downregulated after LSP1 overexpression, indicating LSP1 could suppress HCC growth by inhibiting the ERK pathway in HCC cells. Taken together, these results indicate that LSP1 may serve as a prognostic marker and a potential therapeutic target in human HCC.

Buildings in Southern China widely use a double-skin roof to reduce heat entry through the roof to the building interior during summertime. Concrete roof tiles are preferably installed as the outmost layer of the double-skin roof due to their resistance to hail and wind damages and their attractive price. However, after construction, the tile’s top tends to be darkened by dust deposit and algae growth, increasing the heat entry through the roof to the building. Here, we show that this heat entry can be curtailed by lowering the emissivity at the tile’s underside. Temperatures and heat fluxes at different elevations of a double-skin roof with concrete tiles as the outmost layer of the roof are monitored. The underside of each concrete tile is coated with a specific paint to get a unique emissivity. Observations reveal that lowering the emissivity of concrete roof tiles could cut down the summer heat gain of buildings in tropical regions.

Abstract Background The deregulation of E-cadherin has been considered as a leading cause of hepatocellular carcinoma (HCC) metastasis. BCL6 corepressor-like 1 (BCORL1) is a transcriptional corepressor and contributes to the repression of E-cadherin. However, the clinical significance of BCORL1 and its role in the metastasis of HCC remain unknown. Methods Differentially expressed BCORL1 between HCC and matched tumor-adjacent tissues, HCC cell lines and normal hepatic cell line were detected by Western blot. The expression of BCORL1 was altered by siRNAs or lentivirus-mediated vectors. Transwell assays were performed to determine HCC cell invasion and migration. Results Increased expression of BCORL1 protein was detected in HCC specimens and cell lines. Clinical association analysis showed that BCORL1 protein was expressed at significant higher levels in HCC patients with multiple tumor nodes, venous infiltration and advanced TNM tumor stage. Survival analysis indicated that high expression of BCORL1 protein conferred shorter overall survival (OS) and recurrence-free survival (RFS) of HCC patients. Multivariate Cox regression analysis disclosed that BCORL1 expression was an independent prognostic marker for predicting survival of HCC patients. Our in vitro studies demonstrated that BCORL1 prominently promoted HCC cell migration and invasion. Otherwise, an inverse correlation between BCORL1 and E-cadherin expression was observed in HCC tissues. BCORL1 inversely regulated E-cadherin abundance and subsequently facilitated epithelial-mesenchymal transition (EMT) in HCC cells. Notably, the effect of BCORL1 knockdown on HCC cells was abrogated by E-cadherin silencing. Conclusions BCORL1 may be a novel prognostic factor and promotes cell migration and invasion through E-cadherin repression-induced EMT in HCC.

There are closed pores and dead end pores in red clay, resulting in that the effective pores are less than the actual pores. Therefore, the permeability coefficient calculated according to the traditional Darcy law is greater than the actual value. Based on the traditional Darcy law theory, the empirical calculating formula of the effective porosity-Darcy permeability coefficient is derived by estimating the diameter of the soil particle and the effective porosity. According to the permeation test of different chloride solutions in red clay, the applicability of calculated permeability coefficient of different effective porosity-Darcy law and the actually measured value in red clay is compared. It is found that the permeability coefficient calculated by the traditional Darcy law has a larger deviation from the measured value, and the permeability coefficient calculated by the maximum compaction-Darcy law is consistent with the measured value the most.