A biosensor for D-2-hydroxyglutarate in frozen sections and intraoperative assessment of IDH mutation status.

The oncometabolite D-2-hydroxyglutarate (D-2-HG) has emerged as a valuable biomarker in tumors with isocitrate dehydrogenase (IDH) mutations. Efficient detection methods are required and rapid intraoperative determination of D-2-HG remains a huge challenge. Herein, D-2-HG dehydrogenase from Achromobacter xylosoxidans (AX-D2HGDH) was found to have high substrate specificity. AX-D2HGDH dehydrogenizes D-2-HG and reduces flavin adenine dinucleotide (FAD) bound to the enzyme. Interestingly, the dye resazurin can be taken as another substrate to restore FAD. AX-D2HGDH thus catalyzes a bisubstrate and biproduct reaction: the dehydrogenation of D-2-HG to 2-ketoglutarate and simultaneous reduction of non-fluorescent resazurin to highly fluorescent resorufin. According to steady-state analysis, a ping-pong bi-bi mechanism has been concluded. The Km values for resazurin and D-2-HG were determined as 0.56 µM and 10.93 µM, respectively, suggesting high affinity to both substrates. On the basis, taking AX-D2HGDH and resazurin as recognition and fluorescence transducing element, a D-2-HG biosensor (HGAXR) has been constructed. HGAXR exhibits high sensitivity, accuracy and specificity for D-2-HG in different biological samples. With the aid of HGAXR and the matched low-cost palm-size detecting device, D-2-HG levels in frozen sections of resected brain tumor tissues can be measured in a direct, simple and accurate manner with a fast detection (1-3 min). As the technique of frozen section is familiar to surgeons and pathologists, HGAXR and the portable device can be easily integrated into the current workflow, having potential to provide rapid intraoperative pathology for IDH mutation status and guide decision-making during surgery.

Assessment of effects of climate change and grazing activity on grassland yield in the Three Rivers Headwaters Region of Qinghai-Tibet Plateau, China.

Inter-annual dynamics of grassland yield of the Three Rivers Headwaters Region of Qinghai-Tibet Plateau of China in 1988-2005 was analyzed using the GLO-PEM model, and the herbage supply function was evaluated. The results indicate that while grassland yield in the region showed marked inter-annual fluctuation there was a trend of increased yield over the 18 years of the study. This increase was especially marked for Alpine Desert and Alpine Steppe and in the west of the region. The inter-annual coefficient of variation of productivity increased from the east to the west of the region and from Marsh, Alpine Meadow, Alpine Steppe, Temperate Steppe to Alpine Desert grasslands. Climate change, particularly increased temperatures in the region during the study period, is suggested to be the main cause of increased grassland yield. However, reduced grazing pressure and changes to the seasonal pattern of grazing could also have influenced the grassland yield trend. These findings indicate the importance of understanding the function of the grassland ecosystems in the region and the effect of climate change on them especially in regard to their use to supply forage for animal production. Reduction of grazing pressure, especially during winter, is indicated to be critical for the restoration and sustainable use of grassland ecosystems in the region.

Nitrogen budgets of agricultural fields of the Changjiang River basin from 1980 to 1990.

To assess the fate of the large amounts of nitrogen (N) brought into the agricultural environment by human activities in the Changjiang River basin, we used [China's county level agricultural database of 1980 and 1990. National Resources and Environmental Data Center, China] and published conversion data to set up a complete N budget for the Changjiang River basin. Sources considered include imported N such as atmospheric deposition, inorganic fertilizer, biological fixation and manure. Dominant losses considered include crop harvests, denitrification of soil nitrate and NH3 volatilization, and the budget was estimated from the difference between all inputs and all outputs. Therefore, the geographic distribution of excess N, considered as lost, by N storage in farmland and N transported to water bodies in Changjiang River basin was analyzed. In the Changjiang River basin, the anthropogenic reactive N has far exceeded the terrestrial bio-fixed N in nature, and human activities have significantly altered the N cycle in this region. The total inputs of N in 1980 and 1990 were 8.0 and 12.9 Tg N, respectively. The total N outputs are 4.41 Tg N in 1980 and 6.85 Tg N in 1990. Thus, the excess N that was stored in farmland was 1.51 Tg N at 1980 and 2.67 Tg N at 1990, respectively, and losses through transportation to water bodies in 1980 was 2.08 and 3.38 Tg N in 1990, respectively. Our research shows that from 1980 to 1990, cultivated land increased 5.9%, grain production increased 30% and N fertilizer-use increased 106%, but the N fertilizer-use efficiency decreased 36%, and the variations in the distribution of N fertilizer-use efficiency, N budgets and N transport to water bodies tended to coincide with each other geographically.

Spatio-temporal patterns and driving forces of urban land expansion in China during the economic reform era.

Along with its economic reform, China has experienced a rapid urbanization. This study mapped urban land expansion in China using high-resolution Landsat Thematic Mapper and Enhanced Thematic Mapper data of 1989/1990, 1995/1996 and 1999/2000 and analyzed its expansion modes and the driving forces underlying this process during 1990-2000. Our results show that China's urban land increased by 817 thousand hectares, of which 80.8% occurred during 1990-1995 and 19.2% during 1995-2000. It was also found that China's urban expansion had high spatial and temporal differences, such as four expansion modes, concentric, leapfrog, linear and multi-nuclei, and their combinations coexisted and expanded urban land area in the second 5 y was much less than that of the first 5 y. Case studies of the 13 mega cities showed that urban expansion had been largely driven by demographic change, economic growth, and changes in land use policies and regulations.