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Xiaoping Li,1 Jie Sun,2 Qinghua Xu,1 Weiping Duan,2 Licheng Yang,1 Xing Wu,1 Guang Lu,1 Li Zhang,1 Yunfeng Zheng2 1Department of General Surgery, Liyang People′s Hospital, Jiangsu 213300, People’s Republic of China; 2School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, People’s Republic of ChinaCorrespondence: Xing WuDepartment of General Surgery, Liyang People′s Hospital, No. 70, JianShe West Road, Liyang City, Jiangsu Province, People’s Republic of ChinaTel +86-519-6809-1103Email syj6628@126.comYunfeng ZhengSchool of Pharmacy, Nanjing University of Chinese Medicine, No. 138, Xianlin Ave, Nanjing, Jiangsu Province, People’s Republic of ChinaTel +86-25-8679-8186Email zyunfeng@njucm.comBackground: Colorectal cancer (CRC), a type of highly occurred intestinal cancer at present, is prone to metastasis at the later stage of chemotherapy. Looking for the anti-metastatic agents from natural compounds attracted much concern. Here, it aims to demonstrate whether oxymatrine, an anti-cancer natural compound, has anti-metastatic activity and its potential significance in clinic.Materials and Methods: Wound healing assay and transwell assay were for evaluating the effect of oxymatrine on cell migration and invasion in vitro. Anti-metastatic action in vivo was determined by hepatic metastasis of colorectal cancer cells in mice.Results: Oxymatrine can significantly inhibit cancer cell migration and invasion in vitro. The production of ATP, pyruvate, and lactate was suppressed in CRC cells under the treatment of oxymatrine, as well as the glucose consumption. Meantime, extracellular acidification rates (ECR) were evidently attenuated although the oxygen consumption rates (OCR) were not affected. Both clued that oxymatrine inhibition of metastasis is possibly related to blocking aerobic glycolysis. Subsequent results indicated that pyruvate kinase M2 (PKM2) not hexokinase (HK) and phosphofructokinase (PFK) were involved in oxymatrine blocking glycolysis as the PKM2 kinase activity and expression were inhibited by oxymatrine and the PKM2 activator, TEPP-46, can reverse in part the effect of oxymatrine induced in CRC cells. Furthermore, this process was also mediated by inhibition of glucose transporter 1 (GLUT1). Finally, the in vivo metastatic model in mice showed both 20 mg/kg and 40 mg/kg oxymatrine significantly inhibit liver metastasis of CRC cells in mice, and PKM2 and GLUT1 expression in liver of the oxymatrine-treated group is declined.Conclusion: Oxymatrine exerted anti-metastatic activity dependent on inhibition of PKM2-mediated aerobic glycolysis. It is not only an anti-cancer agent but also a potential anti-metastatic compound with clinical application significance.Keywords: oxymatrine, colorectal cancer, aerobic glycolysis, PKM2, GLUT1

Background Interstitial brachytherapy (IBT) has been introduced as treatment for unresectable pancreatic cancers to maximize local dose and minimize irradiation of surrounding normal tissue. MicroPET-CT systems provide excellent anatomic and molecular information. Purpose To use 18F-FDG micro-positron emission tomography (PET)/computed tomography (CT) to evaluate the therapeutic effect of 125I interstitial brachytherapy on transplantation tumor of human pancreatic carcinoma in Balb/c-nu mice. Material and Methods Xenograft models were created by subcutaneous injection of Swl990 human pancreatic cancer cell suspensions into the immunodeficient Balb/c-nu mice. The study was randomly divided into three groups: control group ( n = 6), empty seed implant group ( n = 6), and 125I seed implant group ( n = 6), respectively. Before and 1 week after treatment, 18F-FDG microPET-CT scan was performed. In-vivo cell proliferation and apoptosis were monitored by thymidine kinase 1 (TK1) immunostaining and Dutp-biotin nick end labeling (TUNEL) assay. Results Our results showed that before treatment the SUVmax and SUVmean values among three groups had no significant statistical difference. One week after treatment the SUVmax and SUVmean in 125I seed implant group were significantly lower than before, while for the empty seed group and control group there were no significant difference compared with before treatment. Immunohistochemical analysis of tumor tissue revealed significantly less TK1 positive cells in 125I seed implant group than in empty seed group and control group. The index of apoptosis was slightly higher in 125I seed implant group than in empty seed group and control group as evaluated by TUNEL assay. Conclusion These results suggest that 18F-FDG microPET-CT may be useful as a non-invasive imaging modality to assess early response to 125I seed brachytherapy in a pancreatic carcinoma Xenograft.

The rapid growth of China's economy has brought about huge losses of natural capital in the form of natural resource depletion and damages from carbon emissions. This paper recalculates value added, capital formation, capital stock, and related multifactor productivity in China's industrial sectors by further developing the genuine savings method of the World Bank. The sector-level natural capital loss was calculated using China's official input–output table and their extensions for tracing final consumers. The capital output elasticity in the productivity estimation was adjusted based on these tables. The results show that although the loss of natural capital in China's industrial sectors in terms of value added has slowed, the impacts on their productivity during the past decades is still quite clear.

A global adaptive output-feedback control scheme is proposed for a class of nonlinear system in output-feedback form with additive output derivative. Unknown parameters are allowed to multiply not only the output nonlinearities but also affine functions of the derivative of the measured output with coefficients that are smooth nonlinear functions of the measured output. Through coordinate transformation and parameter redefinition, the system considered is transformed into the parametric output-feedback canonical form with unknown high-frequency gain sign. To tackle this situation, Nussbaum gain is incorporated in the adaptive backstepping technique. Tuning function method is employed to design the parameter adaptive law to avoid overparametrization. All the signals involved in the closed-loop system can be guaranteed globally uniformly bounded and the asymptotic tracking is achieved. The results of this paper extend the class of uncertain nonlinear systems for which global adaptive output-feedback control can be designed.

A global adaptive output-feedback control scheme is proposed for a class of third-order relative degree nonlinear system with unknown control directions and affine additive output derivative. Trough parameter-dependent coordinate transformation and parameter redefinition, the system considered is transformed into the parametric output-feedback form with known output functions as the virtual control gain functions. To tackle the situation that the unknown high frequency gain sign, Nussbaum gain is incorporated in the adaptive backstepping technique. Tuning function method is employed to design the parameter adaptive law to avoid overparametrization. The closed-loop system can be guaranteed all the signals involved globally uniformly bounded and asymptotic tracking is achieved. The result of this paper enlarges the class of uncertain nonlinear systems for which global adaptive output-feedback control can be designed.