Co-utilization of carbon sources in microorganisms for the bioproduction of chemicals.

Carbon source is crucial for the cell growth and metabolism in microorganisms, and its utilization significantly affects the synthesis efficiency of target products in microbial cell factories. Compared with a single carbon source, co-utilizing carbon sources provide an alternative approach to optimize the utilization of different carbon sources for efficient biosynthesis of many chemicals with higher titer/yield/productivity. However, the efficiency of bioproduction is significantly limited by the sequential utilization of a preferred carbon source and secondary carbon sources, attributed to carbon catabolite repression (CCR). This review aimed to introduce the mechanisms of CCR and further focus on the summary of the strategies for co-utilization of carbon sources, including alleviation of CCR, engineering of the transport and metabolism of secondary carbon sources, compulsive co-utilization in single culture, co-utilization of carbon sources via co-culture, and evolutionary approaches. The findings of representative studies with a significant improvement in the bioproduction of chemicals via the co-utilization of carbon sources were discussed in this review. It suggested that by combining rational metabolic engineering and irrational evolutionary approaches, co-utilizing carbon sources can significantly contribute to the bioproduction of chemicals.

Temperature Monitoring During Microwave Hyperthermia Based on BP-Nakagami Distribution.

OBJECTIVE: The purpose of this study is to accurately monitor temperature during microwave hyperthermia. We propose a temperature estimation model BP-Nakagami based on neural network for Nakagami distribution. METHODS: In this work, we designed the microwave hyperthermia experiment of fresh ex vivo pork tissue and phantom, collected ultrasonic backscatter data at different temperatures, modeled these data using Nakagami distribution, and calculated Nakagami distribution parameter m. A neural network model was built to train the relationship between Nakagami distribution parameter m and temperature, and a BP-Nakagami temperature model with good fitting was obtained. The temperature model is used to draw the two-dimensional temperature distribution map of biological tissues in microwave hyperthermia. Finally, the temperature estimated by the model is compared with the temperature measured by thermocouples. RESULTS: The error between the temperature estimated by the temperature model and the temperature measured by the thermocouple is within 1°C in the range of 25°C-50°C for ex vivo pork tissue, and the error between the temperature estimated by the temperature model and the temperature measured by the thermocouple is within 0.5°C in the range of 25°C-50°C for phantom. CONCLUSIONS: The results show that the temperature estimation model proposed by us is an effective model for monitoring the internal temperature change of biological tissues.

Tumor-associated macrophages recruited by periostin in intrahepatic cholangiocarcinoma stem cells.

Periostin (POSTN) secreted by intrahepatic cholangiocarcinoma stem cells (ICSCs) serves important roles in promoting tumor progression. The present study aimed to investigate POSTN-recruited tumor-associated macrophages (TAMs) in intrahepatic cholangiocarcinoma (ICC). A total of 50 cases were used to investigate the distribution of ICSCs and TAMs in ICC. HCCC-9810 cells were sorted by cluster of differentiation (CD)44, the expression of POSTN of CD44+ (cancer stem cells) and CD44- cells (non-cancer stem cells), and medium were evaluated by western blot analysis. HCCC-9810 cells and THP-1 macrophages were used to detect the effects of POSTN on recruiting TAMs in vitro. The present study revealed that CD44+ cells in ICC tissues and the HCCC-9810 cell line were associated with high POSTN secretion levels. Furthermore, POSTN was associated with TAM density in primary ICC tissues. Additionally, POSTN increased the migration of TAMs derived from THP-1 cells. These findings suggested that POSTN secreted by ICSCs may serve important functions in TAM recruitment, and it may be a potential curative strategy to target the tumor microenvironment in ICC.

Wip1 is associated with tumorigenity and metastasis through MMP-2 in human intrahepatic cholangiocarcinoma.

Wip1 has been shown to correlate with the metastasis/invasion of several tumors. This study was designed to investigate the clinical significance and biological function of Wip1 in intrahepatic cholangiocarcinoma (ICC). The expression of Wip1 was investigated in sixty human ICC biopsy samples by immunohistochemistry. Transient and stable knockdown of Wip1 in two human ICC cells (ICC-9810 and SSP25) were established using short hairpin RNA expression vector. Immunohistochemistry revealed that Wip1 was up-regulated in human ICC tissues (47/60, 78.3%). High levels of Wip1 in human ICC correlated with metastasis to the lymph metastasis (P=0.022). Genetic depletion of Wip1 in ICC cells resulted in significantly inhibited proliferation and invasion compared with controls. Most importantly, Wip1 down-regulation impaired tumor migration capacity of ICC cells in vivo. Subsequent investigations revealed that matrix metalloproteinase-2 (MMP-2) is an important target of Wip1. Consistently, in human ICC tissues, Wip1 level was positively correlated with MMP-2 expression. Taken together, our founding indicates that Wip1 may be a crucial regulator in the tumorigenicity and invasion of human ICC, Wip1 exerts its pro-invasion function at least in part through the MMP-2 signaling pathway, suggesting Wip1 as a potential therapeutic target for ICC.