A Novel Sushi-IL15-PD1 CAR-NK92 Cell Line With Enhanced and PD-L1 Targeted Cytotoxicity Against Pancreatic Cancer Cells.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal malignancy with a limited response to current therapies. Novel and effective treatment is urgently needed. Herein, a chimeric antigen receptor (CAR)-NK92 cell line, with an interleukin (IL)-15Rα-sushi/IL-15 complex and a Programmed cell death-1(PD1) signal inverter was constructed and named SP ( S ushi-IL15- P D1). We showed that CAR expression enabled SP cells to proliferate independently of IL-2 and became more resistant to nutrition starvation-induced apoptosis. Meanwhile, SP cells were more effective than NK92 in PDAC cell killing assays in vitro and in vivo, and there was a positive correlation between the killing capability of SP cells and PD-L1 expression in pancreatic cancer cells. Based on the synergistic and comprehensive effects of the special CAR structure, the adhesion, responsiveness, degranulation efficiency, targeted delivery of cytotoxic granule content, and cytotoxicity of SP cells were significantly stronger than those of NK92. In conclusion, the SP cell line is a promising adoptive immunotherapy cell line and has potential value as an adjuvant treatment for pancreatic cancer, especially in patients with high PD-L1 expression.

[Spatial Distribution of Stable Isotope from the Lakes in Typical Temperate Glacier Region].

We focused mainly on the spatial variation and influencing factors of hydrogen and oxygen stable isotopes between water samples collected at the surface and different depths in the Lashi Lake in August, 2014. Hydrological supply characteristics of the lake in typical temperate glacier region were discussed. The results showed that the values of δ¹8O and δD in the Lashi Lake ranged from -12.98 per thousand to -8.16 per thousand with the mean of -9.75 per thousand and from -99.42 per thousand to -73.78 per thousand with the mean of -82.23 per thousand, respectively. There was a reversed spatial variation between δ¹8O and d. Relatively low values of δ¹8O with high values of d were found at the edge of the lake where the rivers drained into. Meanwhile, the values of d in the vertical profile varied little with depth, suggesting that the waters mixed sufficiently in the vertical direction. The d values increased at first and then decreased from east to west at different layers, but both increase and decrease exhibited different velocities, which were related to the river distribution, the locality of the lake and environmental conditions etc. River water and atmospheric precipitation were the main recharge sources of the Lashi Lake, and the melt-water of snow and ice might also be the supply resource. The δ¹8O values of lake water in glacier region decreased along the elevation (except for Lashi Lake), generally, this phenomenon was called "altitude effect". Moreover, high isotopic values of the lake water from non-glacier region were due to the evaporation effect.

A three generation reproduction study with Sprague-Dawley rats consuming high-amylose transgenic rice.

The transgenic rice line (TRS) enriched with amylose and resistant starch (RS) was developed by antisense RNA inhibition of starch-branching enzymes. Cereal starch with high amylose has a great benefit on human health through its resistant starch. In order to evaluate the effect of transgenic rice on rats, the rats were fed diets containing 70% TRS rice flour, its near-isogenic rice flour or the standard diet as the control through three generations. In the present study, clinical performance, reproductive capacity and pathological responses including body weight, food consumption, reproductive data, hematological parameters, serum chemistry components, organ relative weights and histopathology were examined. Some statistically significant differences were observed in rats consuming the high amylose rice diet when compared to rats fed the near-isogenic control rice diet or the conventional (non-rice) standard diet. These differences were generally of small magnitude, appeared to be random in nature, and were within normal limits for the strain of rat used, and were therefore not considered to be biologically meaningful or treatment related.

[Geochemistry of surface and ground water in the Lijang basin, Northwest Yunnan].

The study focused on the chemical element compositions of river water and groundwater in Lijiang Basin. Water samples were collected in Baishui, Sanshu, Geji and Shuhe rivers in Lijiang Basin to analyze pH, conductivity and ion concentration, in order to understand the contributions of anthropogenic activities and rock weathering to river solutes. The results show that all water samples are mildly alkaline and are rich in Ca2+ and HCO3-, which account for 54.8 and 92.4 percentage of total ion concentration respectively. Obvious variations have been perceived during monsoon and westward wind season. The ion concentration of river water is lower than that of groundwater. With decreasing elevation, the ion concentrations are found to increase considerably in the study region. According to source study of major ions, water chemistry is mainly influenced by precipitation rock weathering and dissolving processes. In addition, precipitation is an important factor in monsoon seasons whereas the anthropogenic inputs have lead to light pollution on water in residential district.

[Chemical composition and daily variation of melt water during ablation season in monsoonal temperate Glacier region: a case study of Baishui Glacier No. 1].

Melt water samples collected continuously from 29 August to 3 September 2009 in the Baishui Glacier No. 1 at elevation of 4750 m were analyzed for pH, conductivity, delta18O and inorganic ions. The results showed that the pH had obvious diurnal variations and was increased slightly by the influence of precipitation. The dissolution of alkaline soluble salts in the dust was the main reason for the increase of melt water conductivity; the value of delta18O was relatively low in strong ablation period and high in slight ablation period. Different from other research areas, the concentrations of Na+, K+, which were influenced by lithological and marine water vapor, were higher than that of Mg2+ in the study area; HCO3- and Ca2+ accounted for more than 80% of total ions in snow and ice melt water, indicating that the ions mainly came from limestone and the melt water was a typical carbonate solution; The content of melt water had an obvious daily change with temperature change, but the response amplitudes were different; Monsoon transport, local rock lithology, human industrial and agricultural activities were the main sources of inorganic ions and the deciding factors of the ion composition in the Baishui Glacier No. 1.

[Characteristics of constant inorganic ions in precipitation at different altitudes precipitation in Yulong Snow Mountain area].

According to the different altitudes precipitation samples in Yulong Snow Mountain area in Yunnan Province from July 26 2005 to July 31 2005, the precipitation chemical characteristics of different altitudes were analyzed with the sea salt iron tracer analysis method. Sea salt tracer analysis showed that Cl-, Na+ had high proportion marine source, amounting 74.79% and 73.53% respectively while the other ions mainly were nonmarine sources. The average percentage of nonmarine sources of NO3-, SO4(2-), K+, Mg2+, Ca2+ were 100%, 93.54%, 97.29%, 81.77%, 99.66%. Statistics chart showed the changes of cation outweigh the anion greatly. The cation concentration ranged between 0.51-5.26 mg/L and anion concentration ranged between 0.99-4.90 mg/L, inferring the cation have more complicated sources. Further analysis showed terrestrial ions, especially near source terrestrial ion composition greatly impact the precipitation ion concentration. Human activities lead to higher anion concentration at alt. 2950-4800 m and precipitation ion concentration was correlated significantly with local atmospheric circulation. The most rock are limestone caused high precipitation cations in Yulong Snow Mountain, such as Ca2+ and Mg2+.

[Character and sources of conventional anion in different water bodies on the summer in Yulong Snow Mountain area].

Different water samples were collected at Mt. Yulong Region located in lijiang city, Yunnan Province from July 22 to July 28 in 2005. The concentration of anion was measured by Dionex-3000 Ion chromatography and Dionex-600 ion chromatography, different water bodies anion composition and concentration in the study area were analyzed by applying approaches of cluster analysis sea salt iron tracer and typical backward trajectories analyze. The results show that the anion concentration of water of altitude higher than 3 180 m takes on natural state and the influence of human activities and foundation rock is less significant. However, human activities and foundation rock exert direct and decisive influence on the anion concentration of water of altitude lower than 3 180 m, with more significant effects than high altitude. Cluster analysis shows that at high altitude anion concentration and composition of water have strong consistency, the consistency of different water bodies in low altitude area anions is weak, indicating the influence factors is more complex in low altitude than high altitude. Sea salt tracer analysis indicates that the average proportion of nonmarine source of Cl- is 65%; NO3- is predominantly of continental origin; nonmarine sources proportion of SO4(2-) is 93.7%. Typical backward trajectories analyze found that the mostly vapor in the region mainly from the Indian Ocean, part of the vapors from the eastern Pacific, the west wind South Branch occasionally along Tibetan Plateau into the study area. SO4(2-) and NO3(-) which from mainly from Southeast Asia and South Asia input with the monsoon circulation.

[Chemical characteristic of water-soluble ions in total suspended particles (TSP) at Lijiang winter time].

25 total suspended particles (TSP) samples were collected at Lijiang city from Dec 2008 to Jan 2009. Analyzed results indicated that the concentration of CU-, NO3-, SO4(2-), Na+ , NH+, K+, Mg2+ and Ca2+ were 16.00, 14.95, 49.40, 3.12, 44.75, 8.65, 29.50 and 183.02 neq x m(-3) respectively. The average total aerosol loading was 349.39 neq x m(-3), and the average concentration of Ca2+ was 52.38% percent of average total concentration, indicated it was the dominant ion in this sampling. The average concentration of detected cations was 3.35 times of anions, suggested the sum of cations generally exceed the sum of anions in our samples, and the main anion was not detected. The average value of SO4(2-)/NO3- was 3.98, showing that the sustained sources have mainly influences on air. According to the correlation coefficients among ions and factor analysis, Ca2+ and Mg2+ in our samples were from dust, and the sources of NO3-, SO4(2-), NH4+ and K+ were related to various combustion processes by human activities. As a whole, the ions in our samples were mainly combined as CaCO3, (NH4)2SO4, MgCO3, KNO3 and a little CaSO4 and Ca(NO3)2.

[Effect of developing tourism on chemical characteristic of precipitation: taking Lijiang for example].

1090 precipitation samples were collected from 1989 to 2006 at Lijiang City. The analyzed results indicate that the average pH value is 6.08 at study period, which is higher than the average pH value (5.0) during 1987 to 1989, and the annual pH value show an increasing trend, suggesting there are more alkaline mass input to air after 1989. the concentrations of major ions Cl-, SO4(2-), NO3-, Na+, Ca2+, Mg2+ and NH4+ are 11.56, 32.64, 3.63, 2.54, 50.19, 7.73 and 11.36 microeq x L(-1), respectively. By computed the correlation coefficients and sources contribution among major ions, it find that Ca2+ and Mg2+ are from soil-derived sources, and about 57.2% of SO4(2-) also come from soil-derived sources; 95.4% of total NO3- and 41.9% of SO4(2-) come from anthropogenic sources, and only Na+ and 25.7% of Cl- come from sea source, meaning that the chemical composition of precipitation at Lijiang region is main influenced by regional sources. According to the variation of tour scale at Lijiang city, it can be divided into 3 periods of 1987-1989, 1989-1996 and 1997-2006. The percent of soil-derived ions at different periods is 40%, 53% and 72%, respectively, showing a significant increase trend; but the percent of anthropology-derived ions at different periods is 39%, 36% and 15%, respectively, showing a decrease trend. It explains that more dust input to the air by expending city scale, changing the land form and overusing water resources. But in order to develop tourism, the pollutants related to industries are controlled well.

[Analysis on chemical compositions of rainwater in summer, Lijiang City, China].

Rainwater samples were colleted from Lijiang City, China, in 23 May-2 July, 2006. Rainwater chemical compositions and sources were studied, using HYSPLIT model, ions tracer techniques, correlation and trend analysis. Total ionic concentration was dominated by SO4(2-) and Ca2+, which account for 65.5% and 15.6% respectively. Sort order of ions concentration is SO4(2-) > Ca2+ > Cl(-) > NO3(-) > Na+ > K+ > Mg2+. Total anions concentration is higher than total cations concentration in 13 rainwater events. The ratio of SO4(2-) to NO3(-) varies from 7.2 to 37.1 and average value is 15.7, it reflected SO4(2-) made great contribution to rainwater acidity in Lijiang City. The correlation among ions is significant due to the atmospheric chemical process and similar ionic sources, and correlation coefficient between SO4(2-) and NO3(-) is 0.74. And what's more, the negative correlation of ionic concentration, precipitation and the average wind speed is also outstanding. The source of NO3(-), SO4(2-), K+ and Ca2+ is mainly land dust, and the non-marine source percent of NO3(-), SO4(2-), K+, Ca2+, Mg2+ and Cl(-) is 100%, 98.8%, 96%, 99.3%, 46.7% and 50.3%, respectively. The main reason of atmospheric environmental variation in Lijing City is pollution caused by economic actions. The pollutants from surrounding industrial parks input into Lijiang City by local circulation, and from industrial regions of Southern Asia, Southeastern Asia and Southeastern China input into Lijiang City by monsoonal circulation.

Global climate change, war, and population decline in recent human history.

Although scientists have warned of possible social perils resulting from climate change, the impacts of long-term climate change on social unrest and population collapse have not been quantitatively investigated. In this study, high-resolution paleo-climatic data have been used to explore at a macroscale the effects of climate change on the outbreak of war and population decline in the preindustrial era. We show that long-term fluctuations of war frequency and population changes followed the cycles of temperature change. Further analyses show that cooling impeded agricultural production, which brought about a series of serious social problems, including price inflation, then successively war outbreak, famine, and population decline successively. The findings suggest that worldwide and synchronistic war-peace, population, and price cycles in recent centuries have been driven mainly by long-term climate change. The findings also imply that social mechanisms that might mitigate the impact of climate change were not significantly effective during the study period. Climate change may thus have played a more important role and imposed a wider ranging effect on human civilization than has so far been suggested. Findings of this research may lend an additional dimension to the classic concepts of Malthusianism and Darwinism.

[Research progress on myogenin gene].

In this paper we briefly introduced the location, structure, polymorphisms of myogenin gene, and discussed the relationships of myogenin gene with economic traits.