The cGas-Sting Signaling Pathway Is Required for the Innate Immune Response Against Ectromelia Virus.

Activation of the DNA-dependent innate immune pathway plays a pivotal role in the host defense against poxvirus. Cyclic GMP-AMP synthase (cGAS) is a key cytosolic DNA sensor that produces the cyclic dinucleotide cGMP-AMP (cGAMP) upon activation, which triggers stimulator of interferon genes (STING), leading to type I Interferons (IFNs) production and an antiviral response. Ectromelia virus (ECTV) has emerged as a valuable model for investigating the host-Orthopoxvirus relationship. However, the role of cGas-Sting pathway in response to ECTV is not clearly understood. Here, we showed that murine cells (L929 and RAW264.7) mount type I IFN responses to ECTV that are dependent upon cGas, Sting, TANK binding kinase 1 (Tbk1), and interferon regulatory factor 3 (Irf3) signaling. Disruption of cGas or Sting expression in mouse macrophages blocked the type I IFN production and facilitated ECTV replication. Consistently, mice deficient in cGas or Sting exhibited lower type I IFN levels and higher viral loads, and are more susceptible to mousepox. Collectively, our study indicates that the cGas-Sting pathway is critical for sensing of ECTV infection, inducing the type I IFN production, and controlling ECTV replication.

Influence of high-carbon basal fertiliser on the structure and composition of a soil microbial community under tobacco cultivation.

Soil microorganisms play a crucial role in cycling soil nutrients and providing organic nutrients for plant growth and development. Fertilisation balances soil fertility and quality, and affects soil microbial communities. Fertilisation is a frontier subject in agricultural and environmental sciences. Here we showed that the application of high-carbon basal fertiliser treatment could improve the tobacco yield and quality when compared to chemical fertiliser, high-carbon basal fertiliser and mixed high-carbon chemical fertiliser. The potential reason is that different fertiliser treatments influence soil fertility, such as nitrogen, phosphorus, and other contents, besides soil organic matter. Further experiments revealed that populations of bacteria, fungi and actinomycetes fluctuated during tobacco development under different fertilisation treatments. Then we performed high-throughput sequencing of the 16S rRNA gene, and the results showed that the fertilisation treatments had significant effects on the microbial community, particularly within the finer taxonomic divisions or non-dominant taxa. Moreover, proteobacteria and fungal genera had significantly different relative abundances during tobacco growth under various tobacco developmental stages and fertilisation treatments. These results indicated that mixed high-carbon chemical fertiliser could improve soil fertility by influencing the soil microorganism, and that the fertilisation treatments impacted on the structure and composition of the microbial community, and especially the diversity of non-dominant taxa. However, more studies are needed to confirm their reliability.

Comparison of Host Gene Expression Profiles in Spleen Tissues of Genetically Susceptible and Resistant Mice during ECTV Infection.

Ectromelia virus (ECTV), the causative agent of mousepox, has emerged as a valuable model for investigating the host-Orthopoxvirus relationship as it relates to pathogenesis and the immune response. ECTV is a mouse-specific virus and causes high mortality in susceptible mice strains, including BALB/c and C3H, whereas C57BL/6 and 129 strains are resistant to the disease. To understand the host genetic factors in different mouse strains during the ECTV infection, we carried out a microarray analysis of spleen tissues derived from BALB/c and C57BL/6 mice, respectively, at 3 and 10 days after ECTV infection. Differential Expression of Genes (DEGs) analyses revealed distinct differences in the gene profiles of susceptible and resistant mice. The susceptible BALB/c mice generated more DEGs than the resistant C57BL/6 mice. Additionally, gene ontology and KEGG pathway analysis showed the DEGs of susceptible mice were involved in innate immunity, apoptosis, metabolism, and cancer-related pathways, while the DEGs of resistant mice were largely involved in MAPK signaling and leukocyte transendothelial migration. Furthermore, the BALB/c mice showed a strong induction of interferon-induced genes, which, however, were weaker in the C57BL/6 mice. Collectively, the differential transcriptome profiles of susceptible and resistant mouse strains with ECTV infection will be crucial for further uncovering the molecular mechanisms of the host-Orthopoxvirus interaction.

αß T-cell receptor bias in disease and therapy (Review).

The diversity and specificity of T cell receptors (TCR), the characteristics of T-cell surface marker, are central to the adaptive immunity. TCR variability is required for successful immunization coverage because this structural foundation is indispensable for the valid identification of short antigen peptides (derived from degraded antigens) that are presented by major histocompatibility molecules on the surfaces of antigen-presenting cells. Despite the vast T-cell repertoire, biased αß TCR has become a common theme in immunology. To date, numerous examples of TCR bias have been observed in various diseases. Immunotherapy strategies that are based on αß T cell responses are also emerged as a prominent component of clinical treatment. In the present review, we briefly summarize the current knowledge regarding basic structural information and the molecular mechanisms underlying TCR diversity. Moreover, we outline the role of TCR repertoire bias in some diseases, and its application for therapeutic interventions, as these play significant roles in disease progression, even with patients with a good prognosis.

Infection of mouse bone marrow-derived immature dendritic cells with classical swine fever virus C-strain promotes cells maturation and lymphocyte proliferation.

In this study, the interactions of classical swine fever virus (CSFV) C-strain and the virulent GSLZ strain with mouse bone marrow-derived immature dendritic cells (BM-imDCs) were investigated for the first time. Both the C-strain and the virulent GSLZ strain could effectively infect and replicate in mouse BM-imDCs. C-strain-infected BM-imDCs showed a greatly enhanced degree of maturation, and could effectively promote the expansion and proliferation of allogeneic naive T cells. The C-strain induced a stronger Th1 response. Infection with the virulent GSLZ strain had no obvious influence on cell maturation or lymphocyte proliferation, and failed to induce any obvious immune response. The results of this study provided initial information for research of the immunologic mechanisms of CSFV using mouse DCs as the model cells.

Sediminicoccus rosea gen. nov. sp. nov., isolated from the sediment of a eutrophic lake.

A polyphasic study was carried out to clarify the taxonomic position of a novel strain R-30(T) isolated from the surficial layer of sediment from Taihu Lake of China. The strain formed pink colored colonies comprising coccodial cells on R2A agar. Phylogenetic analysis based on the 16S rRNA gene sequences showed that strain R-30(T) clustered with the strains of genus Roseococcus and strain Rubritepida flocculans, with Roseococcus suduntuyensis SHET(T) as the closest relative, sharing 95.6% similarity. The major fatty acids (＞5%) were 18：1ω7c (66.7%), 16： 1ω7c/16：1ω6c (10.2%) and 16：0 (8.0%). The major polar lipids were diphosphatidyl glycerol (DPG), phosphatidyl methylethanolamine (PME), phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC). The genomic DNA G+C content was 73.9 mol%. On the basis of the phylogenetic analysis and physiological and biochemical characteristics, we conclude that strain R-30(T) represents a novel genus and species of the family Acetobacteraceae, for which we propose the name Sediminicoccus rosea gen nov. sp. nov. with R-30(T) (= CGMCC 1.12302(T) = NBRC 109675(T)) as the type species and type strain.

[Effects of bone morphogenetic protein and transforming growth fractor-beta on biomechanical property for fracture healing in rabbit ulna].

OBJECTIVE: To investigate the effects of exogenous bone morphogenetic protein (BMP) and transforming growth factor-beta (TGF-beta) on biomechanical property for ulna of fracture healing. METHODS: Thirty-six adult rabbits were made the model of right ulnar fracture and treated locally with TGF-beta/PLA, BMP/PLA, TGF-beta + BMP/PLA or PLA (as control group). Fracture healing was evaluated by measurement of the mechanical parameters and geometric parameters. RESULTS: As compared with control group, the geometric parameters, the bending broken load, the ultimate bending strength, the bending elastic modulus, the ultimate flexural strength, the flexural elastic modulus, the ultimate compressing strength, the compressing elastic modulus, and the ultimate tensile strength for ulna of fracture healing increased significantly in the treatment groups(P < 0.01). These parameters were higher in TGF-beta + BMP/PLA group than in TGF-beta/PLA group or in BMP/PLA group and in TGF-beta/PLA group than in BMP/PLA group(P < 0.05). There was no significant difference in bone density between the treatment groups and control group. CONCLUSION: Local application of exogenous TGF-beta and BMP can increase the callus formation and enhance biomechanical strength of bone after fracture healing. A combination of TGF-beta and BMP has synergetic effect in enhancing fracture healing.

[The expression and imprinting status of insulin-like growth factor 2 gene in colorectal cancer].

OBJECTIVE: To study the imprinting status and expression level of insulin-like growth factor 2 (IGF2) gene in colorectal cancer and to provide a clue for the mechanism of carcinogenesis of colorectal cancer. METHODS: The expression levels of IGF2 in the paired colorectal cancer and adjacent normal tissue were examined and compared by use of semi-quantitative reverse transcription-polymerase chain reaction. The imprinting status of IGF2 was detected by restriction fragment length polymorphism. The relationships between the expression level of IGF2, its imprinting status, and the carcinogenesis of colorectal cancer were analyzed. RESULTS: IGF2 was overexpressed in 82.4% (28/34) of colorectal cancer tissues which was significantly higher than those of the matched normal tissues (P<0.01, t=3.01). 87.5% (14/16) of colorectal cancer showed loss of imprinting(LOI), while 71.4%(10/14) of normal tissues also displayed LOI of IGF2. CONCLUSION: Overexpression of IGF2 was found to play an important role in carcinogenesis of colorectal cancer. LOI of IGF2 may be a prophase manifestation of colorectal cancer.