Progress on structural modification of Tetrandrine with wide range of pharmacological activities.

Tetrandrine (Tet), derived from the traditional Chinese herb Fangji, is a class of natural alkaloids with the structure of bisbenzylisoquinoline, which has a wide range of physiological activities and significant pharmacfological effects. However, studies and clinical applications have revealed a series of drawbacks such as its poor water solubility, low bioavailability, and the fact that it can be toxic to humans. The results of many researchers have confirmed that chemical structural modifications and nanocarrier delivery can address the limited application of Tet and improve its efficacy. In this paper, we summarize the anti-tumor efficacy and mechanism of action, anti-inflammatory efficacy and mechanism of action, and clinical applications of Tet, and describe the progress of Tet based on chemical structure modification and nanocarrier delivery, aiming to explore more diverse structures to improve the pharmacological activity of Tet and provide ideas to meet clinical needs.

Are there differences in the forces driving the conversion of different non-urban lands into urban use? A case study of Beijing.

Examining the heterogeneous factors behind the conversion of various types of non-urban land into urban use is of great significance for controlling urban land expansion and formulating reasonable land use policies. Taking Beijing as an example, this study identified the spatial patterns of urban expansion in China's large cities and then explored the different driving factors behind its various sources. The results showed that, from 2001 to 2010, Beijing's urban land presented a compound expansion mode in which multiple spatial modes coexisted. Urban encroachment contributed differently to the loss of different non-urban lands. Cultivated land and ecological land were the main sources of newly developed urban land, of which the conversion was driven jointly by topography, location, transportation, socioeconomic development, and spatial planning. Moreover, the main factors behind the conversion of various land types varied: closing to existing built-up area and infrastructures increases the conversion probability of most land types; socioeconomic development has common but differentiated effects; governments at different levels have their influences on the conversion of different types of non-urban land. Based on the results, this study suggested the importance of considering varied approaches in managing non-urban lands to better controlling their conversion into urban use and the different roles that could be played by governments at various levels.

Evolving population distribution in China's border regions: Spatial differences, driving forces and policy implications.

The security and socioeconomic development of China's border areas are of great significance to the nation and the wider world. Using census, statistical, digital elevation model (DEM) and network data, this paper employs visual analysis to capture population distribution patterns in China's 131 border counties from 1982 to 2010. Multiple stepwise regression is carried out to identify the influencing factors of population dynamics in border regions. The main findings include: China's most heavily populated border areas are primarily in the northeast, northwest, and the Guangxi-Yunnan region, while rapid growth of population is found in western Inner Mongolia, southwest Xinjiang, northwest Tibet, and southern Yunnan. Given the increasingly market-oriented migration mechanism, the national reclamation policy has been no longer effective in population attraction in the new century. Education has significantly lowered and will continuously lower the fertility rate in remote border areas. The factors influencing population growth show a remarkable regional heterogeneity along China's long border.

Life Expectancy in Chinese Cities: Spatially Varied Role of Socioeconomic Development, Population Structure, and Natural Conditions.

Improving life expectancy, as well as people's health and wellbeing, is an important goal both for the Chinese government and the United Nations. Therefore, to analyze the main factors influencing life expectancy in prefecture-level cities in China, this study uses classical ordinary least-squares regression and geographical weighted regression on the data of the latest census. Moreover, regional differences induced by each influencing factor are also depicted in this study. The results demonstrate that there is significant heterogeneity and spatial positive correlation among the distribution of life expectancy in prefecture-level cities, with a generally higher life expectancy in the provincial capitals and eastern China, and lower in western China. The geographically weighted regression analysis shows that the economic development level, medical conditions, demographic structure, natural environment, and city attributes all affect the distribution of life expectancy, but that their effects have significant spatial heterogeneity. Life expectancy of the less developed areas in Western China is affected dominantly by economic development level, whereas medical services and education are of great importance in determining the life expectancy in Northern and Southern China, respectively. Thus, it is crucial to solve health problems based on local conditions, especially focusing on the improvement of health and health care in underdeveloped areas. Meanwhile, for the eastern developed areas, special attention should be paid to environmental protection in the economic process, while striving to achieve high-quality development.

miR-340 suppresses glioblastoma multiforme.

Deregulation of microRNAs (miRs) contributes to tumorigenesis. Down-regulation of miR-340 is observed in multiple types of cancers. However, the biological function of miR-340 in glioblastoma multiforme (GBM) remains largely unknown. In the present study, we demonstrated that expression of miR-340 was downregulated in both glioma cell lines and tissues. Survival of GBM patients with high levels of miR-340 was significantly extended in comparison to patients expressing low miR-340 levels. Biological functional experiments showed that the restoration of miR-340 dramatically inhibited glioma cell proliferation, induced cell-cycle arrest and apoptosis, suppressed cell motility and promoted autophagy and terminal differentiation. Mechanistic studies disclosed that, miR-340 over-expression suppressed several oncogenes including p-AKT, EZH2, EGFR, BMI1 and XIAP. Furthermore, ROCK1 was validated as a direct functional target miR-340 and silencing of ROCK1 phenocopied the anti-tumor effect of mR-340. Our findings indicate an important role of miR-340 as a glioma killer, and suggest a potential prognosis biomarker and therapeutic target for GBM.

Preclinical safety evaluation of rAd5-hTERTC27 by intravenous injection.

The safety of rAd5-hTERTC27, a replication defective adenovirus vector carrying hTERTC27 for possible use against hepatocellular carcinoma (HCC) was assessed. In single-dose evaluations, intravenous dose levels of up to 2×10(11)VP/kg in rats and 9×10(10)VP/kg in monkeys were well tolerated with no abnormal changes in general signs, body weight and food consumption, and no significant differences in biochemical parameters, urinalysis, ECG, and systemic necropsy observations between the rAd5 groups and solvent control group except that slight hematological change was observed. No hemolytic effect using rabbit blood, local perivasculitis following intravenous injection in rabbits or systemic anaphylaxis in guinea pigs following intravenous dosing was seen. No effects on the central nervous system of mice occurred following intravenous dosing with the exception of an increase in sleep duration at the dose of 1.2×10(11)VP/kg (p<0.05) but not at lower doses of 2×10(10) and 6×10(10)VP/kg in the hypnotic synergism test. These results demonstrate that administration of rAd5-hTERTC27 was well tolerated in an initial set of safety studies as part of an evaluation to allow human trials for the treatment of HCC.

Suppression of tumorigenicity by microRNA-138 through inhibition of EZH2-CDK4/6-pRb-E2F1 signal loop in glioblastoma multiforme.

Deregulation of microRNAs (miRNAs) is implicated in tumor progression. We attempt to identify the tumor suppressive miRNA not only down-regulated in glioblastoma multiforme (GBM) but also potent to inhibit the oncogene EZH2, and then investigate the biological function and pathophysiologic role of the candidate miRNA in GBM. In this study, we show that miRNA-138 is reduced in both GBM clinical specimens and cell lines, and is effective to inhibit EZH2 expression. Moreover, high levels of miR-138 are associated with long overall and progression-free survival of GBM patients from The Cancer Genome Atlas dataset (TCGA) data portal. Ectopic expression of miRNA-138 effectively inhibits GBM cell proliferation in vitro and tumorigenicity in vivo through inducing cell cycles G1/S arrest. Mechanism investigation reveals that miRNA-138 acquires tumor inhibition through directly targeting EZH2, CDK6, E2F2 and E2F3. Moreover, an EZH2-mediated signal loop, EZH2-CDK4/6-pRb-E2F1, is probably involved in GBM tumorigenicity, and this loop can be blocked by miRNA-138. Additionally, miRNA-138 negatively correlates to mRNA levels of EZH2 and CDK6 among GBM clinical samples from both TCGA and our small amount datasets. In conclusion, our data demonstrate a tumor suppressive role of miRNA-138 in GBM tumorigenicity, suggesting a potential application in GBM therapy.

[Experimental study on prevention of postsurgical adhesions by using O-carboxymethylchitosan solution after an abdominal operation].

O-Carboxymethylchitosan (O-CMC) in 1000 g batch was prepared from chitin as starting material and its chemical structure was confirmed by analysis of IR and NMR. O-CMC solution, sodium hyaluronate (HA) solution and physiological saline were used in Sprague-Dawley rat model for prevention of postsurgical adhesions; after 7 days of an abdominal operation, the 3 groups were evaluated according to Belluco standard, the mean scores of O-CMC group, HA group and physiological saline group were 2.5 +/- 3.1, 3.3 +/- 3.6 and 10.3 +/- 1.0, respectively. Histological inspection showed that in O-CMC group, mesothelial cells on peritonaeum or cecum surfaces were almost restored; in HA group the injured surface of peritonaeum was mostly repaired, but in physiological saline group the injured surface of cecum was just a little repaired; there were extensive adhesions between peritonaeum and cecum, and inflammatory response was quite serious. Experimental results indicated that O-CMC and HA had excellent efficiency and O-CMC was slightly better than HA for the prevention of postsurgical adhesions.

Noise and linearity optimization methods for a 1.9GHz low noise amplifier.

Noise and linearity performances are critical characteristics for radio frequency integrated circuits (RFICs), especially for low noise amplifiers (LNAs). In this paper, a detailed analysis of noise and linearity for the cascode architecture, a widely used circuit structure in LNA designs, is presented. The noise and the linearity improvement techniques for cascode structures are also developed and have been proven by computer simulating experiments. Theoretical analysis and simulation results showed that, for cascode structure LNAs, the first metallic oxide semiconductor field effect transistor (MOSFET) dominates the noise performance of the LNA, while the second MOSFET contributes more to the linearity. A conclusion is thus obtained that the first and second MOSFET of the LNA can be designed to optimize the noise performance and the linearity performance separately, without trade-offs. The 1.9GHz Complementary Metal-Oxide-Semiconductor (CMOS) LNA simulation results are also given as an application of the developed theory.