ETS1 deficiency in macrophages suppresses colorectal cancer progression by reducing the F4/80+TIM4+ macrophage population.

Tumor-associated macrophages (TAMs) take on pivotal and complex roles in the tumor microenvironment (TME); however, their heterogeneity in the TME remains incompletely understood. ETS proto-oncogene 1 (ETS1) is a transcription factor that is mainly expressed in lymphocytes. However, its expression and immunoregulatory role in colorectal cancer (CRC)-associated macrophages remain unclear. In the study, the expression levels of ETS1 in CD68+ macrophages in the CRC microenvironment were significantly higher than those in matched paracarcinoma tissues. Importantly, ETS1 increased the levels of chemokines C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 10 (CXCL10) in lipopolysaccharide-stimulated THP-1 cells. It also boosted the migration and invasion of CRC cells during the in vitro co-culture. In the ETS1 conditional knockout mouse model, ETS1 deficiency in macrophages ameliorated the histological changes in DSS-induced ulcerative colitis mouse models and prolonged the survival in an azomethane/dextran sodium sulfate (AOM/DSS)-induced CRC model. ETS1 deficiency in macrophages substantially inhibited tumor formation, reduced F4/80+TIM4+ macrophages in the mesenteric lymph nodes, and decreased CCL2 and CXCL10 protein levels in tumor tissues. Moreover, ETS1 deficiency in macrophages effectively prevented liver metastasis of CRC and reduced the infiltration of TAMs into the metastasis sites. Subsequent studies have indicated that ETS1 upregulated the expression of T-cell immunoglobulin mucin receptor 4 in macrophages through the signal transducer and activator of the transcription 1 signaling pathway activated by the autocrine action of CCL2/CXCL10. Collectively, ETS1 deficiency in macrophages potentiates antitumor immune responses by repressing CCL2 and CXCL10 expression, shedding light on potential therapeutic strategies for CRC.

Loss of Gsdf leads to a dysregulation of Igf2bp3-mediated oocyte development in medaka.

Gonadal soma-derived factor (Gsdf) is a unique TGF-ß factor essential for both ovarian and testicular development in Hd-rR medaka (Oryzias latipes). However, the downstream genes regulated by Gsdf signaling remain unknown. Using a high-throughput proteomic approach, we identified a significant increase in the expression of the RNA-binding protein Igf2bp3 in gsdf-deficient ovaries. We verified this difference in transcription and protein expression against normal gonads using real-time PCR quantification and Western blotting. The genomic structure of igf2bp3 and the syntenic flanking segments are highly conserved across fish and mammals. igf2bp3 expression was correlated with oocyte development, which is consistent with the expression of the igf2bp3 ortholog Vg1-RBP/Vera in Xenopus. In contrast to the normal ovary, cysts of H3K27me3- and Igf2bp3-positive germ cells were dramatically increased in the one-month-old gsdf-deficient ovary, indicating that the gsdf depletion led to a dysregulation of Igf2bp3-mediated oocyte development. Our results provide novel insights into the Gsdf-Igf2bp3 signaling mechanisms that underlie the fundamental process of gametogenesis; these mechanisms may be well conserved across phyla.

Microbial response to CaCO3 application in an acid soil in southern China.

Calcium carbonate (CaCO3) application is widely used to ameliorate soil acidification. To counteract soil and bacterial community response to CaCO3 application in an acidic paddy soil in southern China, a field experiment was conducted with four different dosages of CaCO3 addition, 0, 2.25, 4.5 and 7.5 tons/ha, respectively. After one seasonal growth of rice, soil physicochemical properties, soil respiration and bacterial communities were investigated. Results showed that soil pH increased accordingly with increasing dose of CaCO3 addition, and 7.5 tons/ha addition increased soil pH to neutral condition. Moderate dose of CaCO3 application (4.5 tons/ha) significantly increased soil dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) content, enhanced soil respiration, while the excessive CaCO3 application (7.5 tons/ha) decreased these soil properties. High-throughput sequencing results illustrated that moderate dose of CaCO3 application increased the richness and alpha diversity of soil bacterial community. Compared with control, the relative abundance of Anaerolineaceae family belonging to Chloroflexi phylum increased by 38.7%, 35.4% and 24.5% under 2.25, 4.5 and 7.5 tons/ha treatments, respectively. Redundancy analysis (RDA) showed that soil pH was the most important factor shaping soil bacterial community. The results of this study suggest that proper dose of CaCO3 additions to acid paddy soil in southern China could have positive effects on soil properties and bacterial community.

FSTL3 promotes tumor immune evasion and attenuates response to anti-PD1 therapy by stabilizing c-Myc in colorectal cancer.

Programmed cell death 1 ligand 1 (PDL1)/programmed cell death 1 (PD1) blockade immunotherapy provides a prospective strategy for the treatment of colorectal cancer (CRC), but various constraints on the effectiveness of the treatment are still remaining. As reported in previous studies, follistatin-like 3 (FSTL3) could mediate inflammatory response in macrophages by induction lipid accumulation. Herein, we revealed that FSTL3 were overexpressed in malignant cells in the CRC microenvironment, notably, the expression level of FSTL3 was related to tumor immune evasion and the clinical efficacy of anti-PD1 therapy. Further studies determined that hypoxic tumor microenvironment induced the FSTL3 expression via HIF1α in CRC cells, FSTL3 could bind to the transcription factor c-Myc (354-406 amino acids) to suppress the latter's ubiquitination and increase its stability, thereby to up-regulated the expression of PDL1 and indoleamine 2,3-dioxygenase 1 (IDO1). The results in the immunocompetent tumor models verified that FSLT3 knockout in tumor cells increased the proportion of CD8+ T cells in the tumor microenvironment, reduced the proportion of regulatory T cells (CD25+ Foxp3+) and exhausted T cells (PD1+ CD8+), and synergistically improved the anti-PD1 therapy efficacy. To sum up, FSTL3 enhanced c-Myc-mediated transcriptional regulation to promote immune evasion and attenuates response to anti-PD1 therapy in CRC, suggesting the potential of FSTL3 as a biomarker of immunotherapeutic efficacy as well as a novel immunotherapeutic target in CRC.

Application of modified receptor model for soil heavy metal sources apportionment: a case study of an industrial city, China.

As we all know, geochemical data usually contain outliers and they are heterogeneous, which will severely affect the use of receptor models based on classical estimates. In this paper, an advanced modified RAPCS-RGWR (robust absolute principal component scores-robust geographically weighted regression) receptor model was introduced to analyze the pollution sources of eight heavy metals (Cd, Hg, As, Pb, Ni, Cu, Zn) in a city of southern China. The results showed that source identification and source apportionment are more consistent by this advanced model even though the soil types and farming patterns are diverse. Moreover, this model decreased the occurrence of negative values of the source contribution. For these reasons, the pollution sources were classified into five types by the new model in the study area: agricultural sources, industrial sources, traffic sources, comprehensive sources, and natural sources. (1) The contributions of agricultural sources to Cr and Ni were 243.36% and 242.61%, respectively; (2) the contribution of industrial sources to Cd was 79.25%; (3) the contribution of traffic sources to Cu was 100.31%; (4) the contributions of comprehensive sources to Hg, Pb, and Zn were 253.90%, 242.31%, and 93.32%, respectively; and (5) the contribution of natural sources to As was 208.21%. Overall, the RAPCS-RGWR receptor model improved the validity of the receptor models. It is of great realistic significance to understand and popularize the advanced model in soil source apportionment in agricultural land.

Linkage between soil nutrient and microbial characteristic in an opencast mine, China.

Interaction between soil nutrients and microorganisms makes great contributions to soil quality in mining spoils of fragile ecological environment. While this was not very clear in opencast mine area located in western China. Based on an emerging tool of high-throughput sequencing and a comprehensive analysis method, canonical correlation analysis (CCA), the relationship between microorganisms dominant species and soil nutrients in mined areas located in Loess Plateau of China was studied. The results showed that soil and microbes both developed a lot after reclamation. Mean concentration of soil organic matter (SOM) and total phosphorus (TP) were higher than background value of chestnut soil, while total nitrogen (TN) and total potassium (TK) were lower than that. Soil nutrients and microorganisms in research areas were strongly correlated with each other. SOM, TN, TP, available phosphorus (AP) of soil system and Actinobacteria, Acidobacteria, Bacteroidetes of dominant bacterial species were closely related. Relevant efficient measures should be taken to store soil nutrients thus to activate bacterial performance for sustainable development.

Effects of mycorrhizae and water conditions on perennial ryegrass growth in rare earth tailings.

Mycorrhizal symbioses, which include plant roots and arbuscular mycorrhizal fungi (AMF), can significantly enhance plant resistance and promote the absorption of soil nutrients by plants. A greenhouse experiment was conducted to investigate the effects of three AMF species (Glomus mosses, Glomus etunicatum and Glomus versiforme) on the height, biomass, malondialdehyde (MDA) and proline contents and antioxidant enzyme activities of perennial ryegrass (Lolium perenne) under different water supply treatments. Potted experimental soil samples were collected from the abandoned rare earth tailings in Ganzhou, Jiangxi. The results showed that all three AMF species infected ryegrass under the different treatments. Under severe drought stress, G. mosses had the most significant effects on the promotion of ryegrass performance. After inoculation, the height and whole-plant biomass of ryegrass increased by 60.44% and 150%, respectively. In addition, inoculation with AMF significantly reduced the content of MDA and proline in the ryegrass leaves in all water supply treatments except the moderate drought stress treatment, in which there was no effect. The leaf antioxidant enzyme activity was also measured. The results showed that under severe drought stress, inoculation with Glomus mosses significantly increased the activities of CAT and SOD in ryegrass and enhanced the resistance of plants. A possible reason that AMF promotes host plant growth and enhances drought resistance is that AMF directly increases the absorption of soil water and minerals by host plant roots and indirectly improves the physiological metabolism of plants.

Quantitative correlations between soil and plants in reclaimed mining dumps using a coupling coordination degree model.

It is generally accepted that coevolution between soil and plant has great significance for the sustainable development of mining dumps in fragile eco-environment. However, this was not very clear in opencast mine area located in Western China. Based on comprehensive index systems and a combination of subjective and objective weighting method, a coupling coordination degree model, including comprehensive evaluation function, coupling degree and coupling coordination degree, was established to find the 'short plank' of different reclamation patterns and to quantify the status quo of coevolution between soil and plant systems in mined plots. The results indicated that only the plot with Pinus tabuliformis was under synchronous development, a mixed model of Robinia pseudoacacia-Pi. tabuliformis and R. pseudoacacia monoculture were developed with vegetation lagging, while plots R. pseudoacacia-Ulmus pumila-Ailanthus altissima and original landform were soil lagged. All plots were in the state of primary and intermediate coordination. Thus, some effective measures should be taken for the further development in different patterns.

[Effects of CaCO3 Application on Soil Microbial Nitrogen Cycle in an Acid Soil].

Soil nitrification and denitrification are important steps in closing the nitrogen cycle. Understanding the effects of CaCO3 application on the physicochemical properties and nitrogen cycle in acid soil would provide some theoretical and technical information for stable and sustainable utilization of this agricultural soil. In this study, a field trial was conducted in Xiangtan city, Hunan province. In this field, the soil pH was 5.54, and CaCO3 was applied at four levels: 0, 2.25, 4.5, and 7.5 t·hm-2. After one season of rice cultivation, the soil was sampled to determine dissolved organic carbon (DOC), NH4+-N, and NO3--N levels, and the potential nitrification rate (PNR) and denitrifying enzyme activity (DEA) were measured. The results showed that CaCO3 application improved the content of soil DOC (762.10-868.58 mg·kg-1) and PNR [0.59-0.82 µg·(g·h)-1]. However, excessive application of CaCO3 (7.5 t·hm-2) revealed an obvious inhibition on the activity of soil nitrification. Furthermore, the result of Pearson correlation analysis indicated that soil nitrification was positively correlated with soil DOC and negatively correlated with NH4+-N content, whereas denitrification had a significant positive correlation with NO3--N content and soil DOC, but a negative correlation with water content.