TGFß1 Stimulates Lymphatic Endothelial Cells to Produce IL7 and IL15, Which Act as Chemotactic Factors for Breast Cancer Cells with Mesenchymal Properties.

The lymphatic system is a major gateway for tumor cell dissemination but the mechanisms of how tumor cells gain access to lymphatic vessels are not completely understood. Breast cancer cells undergoing epithelial-mesenchymal transition (EMT) gain invasive and migratory properties. Overexpression of the cytokine transforming growth factor ß1 (TGFß1), a potent inducer of EMT, is frequently detected in the tumor microenvironment and correlates with invasion and lymph metastasis. Recently, we reported that TGFß1 stimulated breast cancer cells with mesenchymal properties to migrate in a targeted fashion towards the lymphatic system via CCR7/CCL21-mediated chemotaxis, similar to dendritic cells during inflammation. Here, we aimed to identify additional chemotactic factors and corresponding receptors that could be involved in guiding breast cancer cells through the lymphatic system. Through a combination of RNA sequencing analysis, database screening and invasion assays we identified IL7/IL7R and IL15/IL15R as pairs of chemokines and receptors with potential roles in promoting chemotactic migration of breast cancer cells with mesenchymal properties towards the lymphatics. The results demonstrate the capacity of TGFß1 to orchestrate crosstalk between tumor cells and lymphatic endothelial cells and warrant further studies to explore the roles of IL7 and IL15 in promoting lymph metastasis of breast cancer.

Nutritional and microbiological effects of vermicompost tea in hydroponic cultivation of maple peas (Pisum sativum var. arvense L.).

Hydroponics receives considerable attentions due to population expansion, soil pollution, and farmland scarcity. However, one significant problem is that its residual effluents are detrimental to the surrounding ecosystem. There is a dire need to find an organic, alternative, biodegradable substrate. Vermicompost tea (VCT) was investigated on its suitability as a hydroponic substrate to provide both nutritional and microbiological benefits. It was found VCT increased the biomass of maple peas (Pisum sativum var. arvense L.), increased stem length, raised the potassium ion content, and promoted the uptake of nitrogen by the roots. Meanwhile, the microorganisms associated with earthworm guts were detected in the maple peas root system, namely the inter-rhizosphere of maple peas, including Enterobacteriaceae, Pseudomonadaceae, and Flavobacteriaceae. The presence of these microorganisms in large number indicated the ability for VCT to retain earthworm intestinal microbes via intestinal tract movement, excreting, and other vital activities. In addition, Rhizobia spp., such as Burkholderiaceae and Rhizobiaceae were also identified in VCT. They are critical for legumes as they can form root or stem nodule symbioses to produce growth hormone, vitamins, nitrogen fixation, and protection against plant stress. These findings are consistent with our chemical analysis that VCT-treated maple peas had increased nitrate and ammonium nitrogen content relative to the control in roots, stems, and leaves, hence increasing maple peas' biomass. The abundance and species of the inter-root bacterial population were found to change during the experimental period, indicating the importance of microbial balance to the growth and nutrient uptake of maple peas.

Visualization Experimental Study on Well Spacing Optimization of SAGD with a Combination of Vertical and Horizontal Wells.

For oil sand reservoirs, the steam-assisted gravity drainage (SAGD) technique is one of the most efficient thermal recovery technologies. However, the high oil viscosity and the severe heat loss seriously affect the production effect of SAGD in developing thin oil sand reservoirs by the traditional SAGD technology. Therefore, it is essential to improve the SAGD technology to enhance the recovery of the thin oil sand reservoir. In this paper, SAGD with a combination of vertical and horizontal well (VH-SAGD) technology was adopted, and the influence of different well spacings (horizontal distance between vertical steam injection wells and horizontal production wells) on the development of steam chambers was investigated. By the similarity criterion, the experimental parameters were obtained. After that, an improved 2D visualization physical model was designed with 9 × 9 high-precision thermocouples installed inside the device to monitor the real-time temperature. This experimental physical model can not only accurately capture the temperature distribution but also display the continuous change process of the chamber inside the model by the visible window. Finally, different well spacing cases (10, 15, and 20 cm) were tested to observe the development of the steam chamber and analyze the production data. Both the temperature distribution and visual window showed that the steam chamber has four obvious stages, and reasonable well spacing can promote the development of the steam chamber. When the well spacing is relatively small, the unswept area of the cold oil on both sides is large, and the area of the steam chamber overlaps more. When the well spacing is relatively moderate, the steam chamber is the most complete and the recovery factor is the highest. When the well spacing is relatively large, although the unswept area of the cold oil on both sides is small, the middle cold oil area is larger than the previous two groups. Therefore, the best well spacing for oil sand reservoirs of about 15 m thickness is 15-20 m, where the VH-SAGD method has a better displacement effect and higher oil recovery. The experimental conclusions can provide theoretical support for the production of thin oil sand reservoirs.

Portable Analytical Techniques for Monitoring Volatile Organic Chemicals in Biomanufacturing Processes: Recent Advances and Limitations.

It is essential to develop effective analytical techniques for accurate and continuous monitoring of various biomanufacturing processes, such as the production of monoclonal antibodies and vaccines, through sensitive and quantitative detection of characteristic aqueous or gaseous metabolites and other analytes in the cell culture media. A comprehensive summary toward the use of mainstream techniques for bioprocess monitoring is critically reviewed here, which illustrates the instrumental and procedural advances and limitations of several major analytical tools in biomanufacturing applications. Despite those drawbacks present in modern detection systems such as mass spectrometry, gas chromatography or chemical/biological sensors, a considerable number of useful solutions and inspirations such as electronic or optoelectronic noses can be offered to greatly overcome the restrictions and facilitate the development of advanced analytical techniques that can target a more diverse range of key nutritious components, products or potential contaminants in different biomanufacturing processes.

FAM122A supports the growth of hepatocellular carcinoma cells and its deletion enhances Doxorubicin-induced cytotoxicity.

FAM122A is a highly conserved protein in mammals, however its function is still largely unknown so far. In this study, we investigated the potential role of FAM122A in hepatocellular carcinoma (HCC). By analyzing HCC patient cohorts from RNA sequencing datasets, we found the expression level of FAM122A mRNA is significantly upregulated in HCC patients. Moreover, this abnormally higher expression pattern of FAM122A protein was also found in partial HCC tumor tissues, compared with the normal parts. Further, we demonstrated that CRISPR/Cas9-mediated FAM122A knockout significantly inhibits the growth, clonogenic potential and xenografts of HCC cells, induces cell cycle arrest and reduces the expression of proliferation-related genes. Interestingly, FAM122A deletion significantly enhances the cytotoxicity effect of Doxorubicin (Dox), a drug used in standard chemotherapy in HCC patients. In contrary, overexpression of FAM122A not only promotes HCC cell growth, but also inhibits Dox-induced DNA damage and cell death. Considering that FAM122A is previously identified as an endogenous inhibitor of PP2A, we asked whether FAM122A regulating HCC cell growth is associated with PP2A. The results showed FAM122A can also modulate PP2A activity in HCC cells although the modulated effect is relatively slight, however, treatment with a PP2A inhibitor okadaic acid did not rescue the inhibitory effects of cell growth and proliferation in FAM122A deletion cells, indicating that FAM122A may support HCC cell growth independent of its ability to modulate PP2A. Collectively, these results suggest that FAM122A is required for maintaining HCC cell growth, and its elimination combined with chemotherapy may represent a potential novel therapeutic strategy for HCC patients.