Targeting IRG1 reverses the immunosuppressive function of tumor-associated macrophages and enhances cancer immunotherapy.

Immune-responsive gene 1 (IRG1) encodes aconitate decarboxylase (ACOD1) that catalyzes the production of itaconic acids (ITAs). The anti-inflammatory function of IRG1/ITA has been established in multiple pathogen models, but very little is known in cancer. Here, we show that IRG1 is expressed in tumor-associated macrophages (TAMs) in both human and mouse tumors. Mechanistically, tumor cells induce Irg1 expression in macrophages by activating NF-κB pathway, and ITA produced by ACOD1 inhibits TET DNA dioxygenases to dampen the expression of inflammatory genes and the infiltration of CD8+ T cells into tumor sites. Deletion of Irg1 in mice suppresses the growth of multiple tumor types and enhances the efficacy of anti-PD-(L)1 immunotherapy. Our study provides a proof of concept that ACOD1 is a potential target for immune-oncology drugs and IRG1-deficient macrophages represent a potent cell therapy strategy for cancer treatment even in pancreatic tumors that are resistant to T cell-based immunotherapy.

[Effects of climate warming on the N2O emission from Larix gmelinii forest soils at different latitudes during soil thawing period].

During the soil thawing period in spring, large amount of N2O was emitted from the forest soils in North China, being a major source of atmospheric greenhouse gases. However, the contribution of the emitted N2O and its responses to climatic change are unclear. In this paper, sampling plots of Larix gmelinii forest (including sapling, ground vegetation, and soil A and B horizons) with similar stand conditions in Tahe (52 degrees 31' N), Songling (50 degrees 43' N), Sunwu (49 degrees 13' N), and Dailing (47 degrees 05' N) were displaced to the south boundary of L. gmelinii natural distribution area to simulate that the plots were under climate warming, and their N2O fluxes were measured during the soil thawing period in spring 2007. For the four plots, the N2O fluxes all peaked at the mid- or late stage of soil thawing. The N2O flux of the plots from Dailing, Suwu, Songling, and Tahe during soil thawing period was averagely 66.5 +/- 9.3, 54.3 +/- 5.6, 44.3 +/- 5.3, and 33.5 +/- 3.7 microg x m(-2) h(-1), respectively, and significantly positively correlated to the soil temperature at 5 cm depth and the soil microbial biomass carbon at 0-10 cm depth. No significant relationship was observed between the N2O flux and soil moisture content. The soil N2O emission during soil thawing period differed significantly among the plots. Both the mean N2O flux and the cumulative N2O emission decreased with increasing latitude, mainly due to the differences in soil microbial activities and soil physical properties.

[Soil nitrous oxide emission in four temperate forests in northeastern China].

Seasonal dynamics of N2O flux and its controlling factors for four representative temperate forests in northeastern China were examined with a static closed chamber-gas chromatograph technique. These forests were Korean pine (Pinus koraiensis) plantation, Dahurian larch (Larix gmelinii) plantation, Mongolian oak ( Quercus mongolica) forest and hardwood broadleaved forest (dominated by Fraxinus mandshurica, Juglans mandshurica, and Phellodendron amurense). The results showed that all ecosystems were overall atmospheric N2O source during the growing season. The N2O flux (microg x m(-2) x h(-1)) decreased in order of the hardwood broadleaved forest (21.0 +/- 4.9) > the pine plantation (17.6 +/- 4. 6) > the larch plantation (9.8 +/- 5.9) > the oak forest (1.6 +/- 12.6). Overall, there was no consistent seasonal pattern in N2O flux for the four ecosystems. The N2O flux was significantly positively correlated to soil gravimetric water content (0-10 cm depth) consistently for all ecosystems, but significantly negatively correlated to NO3(-)-N content for each ecosystem. However, the responses of N2O flux to soil temperature and NH4(+)-N differed among the ecosystems. The N2O fluxes for the coniferous plantations were positively correlated to NH4(+)-N, but not correlated to the soil temperature at 5 cm depth; while those for the broadleaved forests displayed an opposite trend. The soil water content was the dominator of soil N2O emission for the forests in 2007 perhaps resulting from relative drought in the year. Interactions of vegetation type, environmental factor, and nitrogen availability to soil N2O emission should be further studied in the future.

[Study on the interface of Ti-porcelain fused under different surface treatment].

OBJECTIVE: This study was made to observe the topography and ionic diffusion of the elements titanium, silicon, et cetera in the Ti-porcelain interface area which was pretreated with different methods. METHODS: Ti-bond porcelain was fused on commercial pure titanium (CPT) with 8 different pretreatment methods; according to the temperature of the preoxidation, there were 300 degrees C, 400 degrees C, 500 degrees C and 600 degrees C groups, and based on the oxidizing-time in the air, there were 5 min, 15 min, 2 h and 24 h groups. The topography and ionic diffusion of elements in the Ti-porcelain interface area were observed with scanning electron microscopy (SEM) and electron probe microanalysis (EPMA) respectively. RESULTS: There were clefts and exfoliations in the 500 degrees C pre-oxidation group and 600 degrees C pre-oxidation group in SEM images. The distribution of titanium in the interlayer in EPMA images decreased from the titanium surface to porcelain, which was opposite to the distribution of silicon. CONCLUSION: The clefts and exfoliations suggested the position of the fracture and brittleness of alpha-Ti[o] layer. The widths of ionic diffusion in the eight groups were different, but it was difficult to measure and compare them exactly.