Pan-cancer analysis reveals distinct clinical, genomic, and immunological features of the LILRB immune checkpoint family in acute myeloid leukemia.

Leukocyte immunoglobulin (Ig)-like receptor Bs (LILRBs), a family of type I transmembrane glycoproteins, are known to inhibit immune activation. Here, we comprehensively evaluated the molecular, prognostic, and immunological characteristics of LILRB members in a broad spectrum of cancer types, focusing on their roles in acute myeloid leukemia (AML). We showed that LILRBs were significantly dysregulated in a number of cancers and were associated with immune-inhibitory phenotypes. Clinically, high expression of LILRB1-LILRB4 predicted poor survival in six independent AML cohorts. Genetically, LILRB1 was associated with more mutational events than other LILRB members, and multiple genes involved in immune activation were deleted in LILRB1 high patients. Epigenetically, LILRB4 was significantly hypomethylated and marked by MLL-associated histone modifications in AML. Immunologically, LILRBs were positively associated with monocytic cells, including M2 macrophages, but were negatively associated with tumor-suppressive CD8 T cells. Importantly, patients with higher LILRB expression generally showed a better response to immune checkpoint blockade (ICB) in five independent immunotherapy cohorts. Our findings reveal critical immunological and clinical implications of LILRBs in AML and indicate that LILRBs may represent promising targets for immunotherapy of AML.

Clinical and prognostic relevance of CXCL12 expression in acute myeloid leukemia.

BACKGROUND: Accumulating studies have been made to understand the association between CXC chemokine ligand-12 (CXCL12)/CXC chemokine receptor 4 (CXCR4) and acute myeloid leukemia (AML). However, large-scale data analysis of potential relationship between CXCL12 and AML remains insufficient. METHODS: We collected abundant CXCL12 expression data and AML samples from several publicly available datasets. The CIBERSORT algorithm was used to quantify immune cell fractions and the online website of STRING was utilized for gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The statistical analysis and graphical work were mainly performed via the R software. RESULTS: CXCL12 expression was extremely down-regulated in AML. Clinically, low CXCL12 expression was correlated with higher white blood cells (WBCs) (P < 0.0001), more blasts in bone marrow (BM) (P < 0.001) and peripheral blood (PB) (P < 0.0001), FLT3-internal tandem duplications (FLT3-ITD) (P = 0.010) and NPM1 mutations (P = 0.015). More importantly, reduced CXCL12 expression predicted worse overall survival (OS) and event-free survival (EFS) in all AML, non-M3-AML, and cytogenetically normal (CN)-AML patients in three independent cohorts. As for immune cell infiltration, high CXCL12 expressed groups tended to harbor more memory B cells and plasma cells infiltration while low CXCL12 expressed groups exhibited more eosinophils infiltration. GO enrichment and KEGG pathways analysis revealed the potential biological progress the gene participating in. CONCLUSIONS: CXCL12 is significantly down-regulated in AML and low CXCL12 expression is an independent and poor predictor of AML prognosis. CXCL12 expression level correlates with clinical and immune characteristics of AML, which could provide potential assistance for treatment. Prospective studies are needed to further validate the impact of CXCL12 expression before routine clinical application in AML.

The M2 macrophage marker CD206: a novel prognostic indicator for acute myeloid leukemia.

Hematological malignancies possess a distinctive immunologic microenvironment compared with solid tumors. Here, using an established computational algorithm (CIBERSORT), we systematically analyzed the overall distribution of 22 tumor-infiltrating leukocyte (TIL) populations in more than 2000 bone marrow (BM) samples from 5 major hematological malignancies and healthy controls. Focusing on significantly altered TILs in acute myeloid leukemia (AML), we found that patients with AML exhibited increased frequencies of M2 macrophages, compared to either healthy controls or the other four malignancies. High infiltration of M2 macrophages was associated with poor outcome in AML. Further analysis revealed that CD206, a M2 marker gene, could faithfully reflect variation in M2 fractions and was more highly expressed in AML than normal controls. High CD206 expression predicted inferior overall survival (OS) and event-free survival (EFS) in two independent AML cohorts. Among 175 patients with intermediate-risk cytogenetics, the survival still differed greatly between low and high CD206 expressers (OS; P < .0001; 3-year rates, 56% v 32%; EFS; P < .001; 3-year rates, 47% v 25%). When analyzed in a meta-analysis, CD206 as a continuous variable showed superior predictive performance than classical prognosticators in AML (BAALC, ERG, EVI1, MN1, and WT1). In summary, M2 macrophages are preferentially enriched in AML. The M2 marker CD206 may serve as a new prognostic marker in AML.

[Construction, expression and immunogenicity of EV71 multiepitope-mGITRL eukaryotic plasmid].

AIM: To construct an enterovirus 71(EV71) multiepitope-mGITRL eukaryotic plasmid and study its immunogenicity in BALB/c mice. METHODS: We first designed and synthesized VP1' epigene containing two B cells and two T cells epitopes of VP1, and amplified mGITRL gene by PCR. The VP1' epigene and mGITRL gene were then cloned into the expression vector pIRES to construct the recombination plasmid pIRES-VP1'-mGITRL. The recombination plasmid was transfected into COS7 cells by liposome-mediated method. The protein expressions of VP1' and mGITRL were detected by Western blotting. BALB/c mice were immunized with pIRES-VP1'-mGITRL plasmid, and its serum antibody titer was measured by ELISA. RESULTS: The recombination plasmid pIRES-VP1'-mGITRL was successfully constructed as demonstrated by sequencing. Western blot analysis indicated that the VP1'-mGITRL fusion protein was expressed in COS7 cells and muscle cells. After BALB/c mice were immunized with this plasmid, we detected the high titer of anti-VP1 antibody in serum. CONCLUSION: VP1'-mGITRL fusion protein can be highly expressed in COS7 cells and muscle cells by the construction and transfection of the recombination plasmid pIRES-VP1'-mGITRL, and it could elicit the dramatic immune response in mice.

[Identification of different corrosion covering the surface of Chinese ancient lead glazed potteries].

In the present paper, different corrosions of three pieces of Chinese ancient lead glazed potteries from different burial circumstances were analyzed by using XRD, FTIR, EDXRF, RS etc, and the analyses indicate that the main crystalline phase of corrosion of HYT is cerussite (PbCO3), that of SYT is calcium-lead hydroxyapatite [Pb(10-x) Ca(x) (PO4)(OH)2 (x < 2.7)] and the yellow area of the erosion is attributed to a certain mount of iron oxide, that of TSC is the cerussite (PbCO3) and calcium-lead hydroxyapatite [Pb(10-x)Ca(x) (PO4) (OH)2 (x < 2.7)], and the brown-black area of the erosion product is the result of the existence of little mount of iron and carbon black.

[Preliminary study on the function of potteries of Liangzhu Culture].

Liangzhu Culture is an important late neolithic culture of China, but there are different opinions on the function of some potteries of Liangzhu Culture, for example vat and Ding. In the present paper, for discussing the function of these potteries, the content of Cl, Ca and P of some shard samples of vat and Ding from Liangzhu site were analyzed by using EDXRF line scanning technology. The results show that the content of element Cl in the outside and inside parts of the bottom of vat sample is not different from that of other contemporaneous archaic potteries, and that the distribution of element Cl in the outside part of the bottom of vat sample is the same as that in the inside part of the bottom, so it is concluded that the function of vat from Liangzhu Culture is not related to the production or storage of salt, but with regard to the true function of this pottery more works remain to be done. The analytical results also show that the content of two elements, Ca and P, in the bottom of the other pottery, Ding, is obviously higher than that in vat and other contemporaneous archaic potteries, and that the content of two elements, Ca and P, in the outside part of the bottom of Ding sample is higher than that in the inside part of the bottom. So it is concluded that Ding from Liangzhu Culture is a kind of cooking ware and its main function is meal cooking.

[A primary Raman microscopic study of the turquoise and its role in provenance-tracking].

The authors analyzed four modern turquoises from Hubei province and Anhui province by using the Raman microscopic with the samples are gathered on the spot. According to the study the authors discovered that the Raman spectra of the Hubei turquoises with different color but with the same backgrounds of mineral resource and the formation cause of mineral resource and in the same formation line of turquoise mineral resource have little difference. On the contrary, there is a strong difference in the 900-100 cm(-1) region of the Raman spectra between the turquoises from Hubei province and the turquoise from Anhui province which has remarkable different backgrounds of mineral resource and the formation cause of mineral resource. At the same time the authors studied two ancient turquoises to discuss the feasibility of using the Raman spectra of turquoises, the provenance of which is known, as the fingerprint directions to track the provenance of ancient turquoises.

[Spectral analysis of ceramic-painting pigments from Taosi site].

Based on the analysis of Raman, IR spectroscopy and XRD methods, the structure of the different pigments and bond in red pigment in the ceramic from Taosi site in Xiangfeng county, Shanxi province was analyzed. It is very prominent that both red and white pigments have been well preserved. The red pigment was identified as HgS, while white pigment is CaCO3, and the bond in red pigment is CaCO3, which was made from white lime, and the reasons for its formation is because of carbon dioxide in air, which was absorbed by white lime over long history. Moreover, it was indicated that the Raman and IR spectra are more effective for identifying the ancient pigments in very few quantities than XRD. Furthermore, the fact that quartz was unfound in vermilion, suggested that the technique for synthetic vermilion might have been known in 4 000 years ago in Taosi site.

[Study on colored drawing technique of Qionglai kiln by SRXRF].

The colored drawing technique of Qionglai kiln is a debate problem in the archaeology and ancient ceramic research. In the present paper, SRXRF linescan technology was used to study the distribution mode of the colorific elements on the cross-sections of samples. The analytical result indicates that there existed two kinds of decoration techniques of colored drawing, i. e. the techniques of the underglaze color and oveglaze color coexisted in that time.

[X-ray fluorescence analysis in archaeometry: application and expectation].

This article describes the applications of X-ray fluorescence in archaeology research, including the appraisal, dating, provenance and mine material origin analysis of cultural relic, the study of manufacturing technics and production of cultural relic, etc. It also suggests some expectation and problems, in order to draw attention of X-ray fluorescence analysts and archaeologists, promote the in-depth development of X-ray fluorescence analysis application in archaeology research, and further make more contributions to Chinese archaeology research.

[Line scanning analysis of white porcelain from Gong Kiln in early Tang dynasty by energy disperse X-ray fluorescence].

Gong kiln, for its long porcelain-firing history, was one of three representative white porcelain kilns in northern China. In order to improve the quality and whiteness of white porcelain, a decorating layer or cosmetic earth was laid on the body surface in Gong kiln during early Tang dynasty, which was able to blot out rough surface and weaken the influence of fuscous body upon surface color. In this paper the main chemical composition of the white porcelain's profile was analyzed by using energy disperse X-Ray fluorescence. The result showed that different materials were used as cosmetic earth during early Tang dynasty, in accordance with the phenomenon under optical microscope. In addition, the glaze belongs to calcium glaze in which plant ash was added.

[The application of trace element analysis to the study of provenance of copper minerals in ancient bronzes].

The simulated smelting and founding experiment of bronze showed that the copper minerals from different regions could be distinguished clearly by using the multi-statistical analysis based on choosing the chalcophile elements determined by ICP-AES. In the present paper, the data of trace elements in bronzes from Panlongcheng Site and Ezhou, which were determined by NAA, were tried to be processed. The analytical result showed that the bronzes from Panlongcheng and Ezhou could be divided clearly, just like the results of the former simulated smelting and founding experiment of bronze. So, the feasibility of trace element analysis for the study of provenance of copper minerals in ancient bronzes was proved again.

[Plane scan analysis of the surface of white and blue porcelain by SRXRF method].

In this article, the authors analyze the surface of a piece of porcelain shred in Xuande Period by SRXRF, and the result shows that each peak area of elements differs in distribution pattern. According to the relationship between element peak area and color variation, and yellow fleck in glaze, it is possible to divide 13 elements, i.e. K, Cr, Mn, Fe, Co, Ni, Cu, Zn, Hg, Rb, Sr, Y and Zr, into three groups. This phenomenon will indicate how to search the "finger elements" in each dynasty; at the same time, it will present important information for research on the forming mechanism of yellow flecks in glaze.