Abstract Apixaban is a highly potent, selective, and efficacious inhibitor of blood coagulation factor Xa. A practical and efficient process has been developed for the preparation of the key intermediate ( G ) of Apixaban. Starting from inexpensive 4-chloronitrobenzene and piperidine, an eight-step procedure for G has been developed. In this case, sodium chlorite is used twice to oxidize the piperidine cycle to the corresponding lactam under a CO 2 atmosphere, resulting in the construction of two lactams. Furthermore, most of these reactions are highly efficient and practical as they occur under mild conditions. Most of the intermediates can be obtained through simple slurry or recrystallization, and column chromatography purification is not necessary.
Background Over the past two decades, major epidemics of hand, foot, and mouth disease (HFMD) have occurred throughout most of the West-Pacific Region countries, causing thousands of deaths among children. However, few studies have examined potential determinants of the incidence of HFMD. Methods Reported HFMD cases from 2912 counties in China were obtained for May 2008. The monthly HFMD cumulative incidence was calculated for children aged 9 years and younger. Child population density (CPD) and six climate factors (average-temperature [AT], average-minimum-temperature [ATmin], average-maximum-temperature [ATmax], average-temperature-difference [ATdiff], average-relative-humidity [ARH], and monthly precipitation [MP]) were selected as potential explanatory variables for the study. Geographically weighted regression (GWR) models were used to explore the associations between the selected factors and HFMD incidence at county level. Results There were 176,111 HFMD cases reported in the studied counties. The adjusted monthly cumulative incidence by county ranged from 0.26 cases per 100,000 children to 2549.00 per 100,000 children. For local univariate GWR models, the percentage of counties with statistical significance (p<0.05) between HFMD incidence and each of the seven factors were: CPD 84.3%, ATmax 54.9%, AT 57.8%, ATmin 61.2%, ARH 54.4%, MP 50.3%, and ATdiff 51.6%. The R2 for the seven factors' univariate GWR models are CPD 0.56, ATmax 0.53, AT 0.52, MP 0.51, ATmin 0.52, ARH 0.51, and ATdiff 0.51, respectively. CPD, MP, AT, ARH and ATdiff were further included in the multivariate GWR model, with R2 0.62, and all counties show statistically significant relationship. Conclusion Child population density and climate factors are potential determinants of the HFMD incidence in most areas in China. The strength and direction of association between these factors and the incidence of HFDM is spatially heterogeneous at the local geographic level, and child population density has a greater influence on the incidence of HFMD than the climate factors.
Thermokarst lake development significantly affects hydrologic systems, infrastructure stability, and greenhouse gas emissions. However,  the spatial and temporal changes, carbon emissions patterns, and motivators in thermokarst lakes remain largely unknown. In this study, we created a thermokarst lake dataset on the Qinghai-Tibet Plateau (QTP) using a threshold-based mapping method based on Google Earth Engine (GEE) data associated with visual inspection. In addition, we measured CH4 and CO2 diffusive fluxes in 163 thermokarst lakes in the QTP over 3 years from May to October. Our results showed that thermokarst lakes on the QTP permafrost region covered a total area of 1572 ± 184 km2, with most of the thermokarst lakes
The temporal variation of sedimentary organic matters (SOM) in the East China Sea (ECS) is not fully assessed due to the complicated natural and anthropogenic processes. In this study, the compositions and distributions of multi-biomarker indicators (n-alkanes, n-alkanols and specific sterols) in a long sediment core collected from the Min-Zhe fined-grained sediment zone of the ECS were systematically studied to reveal variations of SOM sources and phytoplankton records over the last decades. The results of n-alkanes and sterols have demonstrated that terrestrial plants are the dominant SOM source, with the mean proportion of 67%. The temporal variation of terrestrial to marine biomarker ratios (TMBR) agree well with that of the dominant n-alkanes and terrigenous/aquatic ratios (TAR), suggesting that the multi-biomarker indicators yield a better assessment of the SOM source input. The regular variations of terrestrial OM and phytoplankton signals during the past decades record the interaction among marine ecological effects, anthropogenic activities and natural processes (i.e., extreme climate events). As a whole, the elevated productivity of marine phytoplankton since 1952 (mainly caused by enhanced nutrient inputs owing to the intensified human activities) and the decline in the period of 2005–2011 (likely influenced by the water impoundment of the Three Gorges Dam in 2003) were well reconstructed on the basis of brassicasterol (B) and dinosterol (D) indicators in this study. The B/(B + D) ratios also reveal the changes of community structure as a result of variations in the nutrient structure controlled by anthropogenic forcing. Notably, the anomalous peak in the abundance of n-alkanes with the even carbon predominance in about 1990 is identified for the first time, which may occur at that time of the first heavy rainfall after a long drought and is probably of the origin of biomass/fossil fuel combustion.
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