A concise chemoenzymatic total synthesis of neutral Globo-series glycosphingolipids Globo A and Globo B, and Forssman and para-Forssman antigens.

Globo A is a neutral Globo-series glycosphingolipid (GSL) that shows natural properties of a cytotoxicity receptor NKp44 binding ligand. The highly complex heptasaccharide glycan structure of Globo A combined with its biological profile provides a unique target for the development of a synthetic method to facilitate its bioactivity studies. Here, a concise chemoenzymatic route to the synthesis of Globo A and its α1,3-galactose-linked congener Globo B is reported. The key to success was the use of a synthetic azido ß-Globo H sphingosine (Globo H-ßSph) as an acceptor substrate and two glycosyl transferases, an α1,3-N-acetylgalactosaminyltransferase from Helicobacter mustelae (BgtA) and a human blood group B α1,3-galactosyltransferase (h1,3GTB), for stereoselective construction of the terminal α1,3-GalNAc and α1,3-Gal linkages, respectively. The azido-Sph lipid sidechain is further elaborated by reduction and a chemoselective N-acylation to complete the total synthesis of the neutral Globo-series GSLs. In addition, the synthesis of Forssman and para-Forssman antigens were prepared. The strategy may be suitable for accessing other complex GSLs and related lipid-modified GSL derivatives.

Chemoenzymatic Synthesis of DSGb5 and Sialylated Globo-series Glycans.

Sialic-acid-binding, immunoglobulin-type lectin-7 (Siglec-7) is present on the surface of natural killer cells. Siglec-7 shows preference for disialylated glycans, including α(2,8)-α(2,3)-disialic acids or internally branched α(2,6)-NeuAc, such as disialosylglobopentaose (DSGb5). Herein, DSGb5 was synthesized by a one-pot multiple enzyme method from Gb5 by α2,3-sialylation (with PmST1) followed by α2,6-sialylation (with Psp2,6ST) in 23 % overall yield. DSGb5 was also chemoenzymatically synthesized. The protection of the nonreducing-end galactose of Gb5 as 3,4-O-acetonide, 3,4-O-benzylidene, and 4,6-O-benzylidene derivatives provided DSGb5 in overall yields of 26 %, 12 %, and 19 %, respectively. Gb3, Gb4, and Gb5 were enzymatically sialylated to afford a range of globo-glycans. Surprisingly, DSGb5 shows a low affinity for Siglec-7 in a glycan microarray binding affinity assay. Among the synthesized globo-series glycans, α6α3DSGb4 shows the highest binding affinity for Siglec-7.

Exploring the Moderating Effect of Positive and Negative Word-of-Mouth on the Relationship between Health Belief Model and the Willingness to Receive COVID-19 Vaccine.

This study indicates that the positive and negative effects of word-of-mouth (WOM) have an impact and moderating effect on vaccine uptake willingness, which is important to exploring the factors that affect vaccine uptake. We further analyzed the differences in the impact relationship between variables through questionnaire research. Based on the Health Belief Model (HBM) widely used to explore global health issues, this study focuses on Taiwanese residents and uses a questionnaire survey method. Furthermore, this study investigates the impact of various factors in the HBM on the willingness to receive the COVID-19 vaccine when faced with positive and negative word-of-mouth evaluations from the perspective of vaccine recipients, as well as whether WOM evaluations have an interference effect, along with the differences between variables. Practical recommendations are provided based on the research results, which can serve as a reference for future vaccine promotion programs and health promotion. By improving the national vaccination rate and achieving herd immunity, we aim to increase the persuasiveness of word-of-mouth on public healthcare decision-making. We also hope to provide a basis for health promotion and encourage people to make informed decisions about vaccination.

High expression of embryonic stem cell marker SSEA3 confers poor prognosis and promotes epithelial mesenchymal transition in hepatocellular carcinoma.

BACKGROUND: Malignant cells may arise from dedifferentiation of mature cells and acquire features of the progenitor cells. Definitive endoderm from which liver is derived, expresses glycosphingolipids (GSLs) such as stage-specific embryonic antigen 3 (SSEA3), Globo H, and stage-specific embryonic antigen 4 (SSEA4). Herein, we evaluated the potential prognosis value of the three GSLs and biological functions of SSEA3 in hepatocellular carcinoma (HCC). METHODS: The expression of SSEA3, Globo H, and SSEA4 in tumor tissues obtained from 328 patients with resectable HCC was examined by immunohistochemistry staining. Epithelial mesenchymal transition (EMT) and their related genes were analyzed by transwell assay and qRT-PCR, respectively. RESULTS: Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with higher expression of SSEA3 (p < 0.001), Globo H (p < 0.001), and SSEA4 (p = 0.005) and worse overall survival (OS) for those with high expression of either SSEA3 (p < 0.001) or SSEA4 (p = 0.01). Furthermore, multivariable Cox regression analysis identified the SSEA3 as an independent predictor for RFS (HR: 2.68, 95% CI: 1.93-3.72, p < 0.001) and OS (HR: 2.99, 95% CI: 1.81-4.96, p < 0.001) in HCC. Additionally, SSEA3-ceramide enhanced the EMT of HCC cells, as reflected by its ability to increase migration, invasion and upregulate the expression of CDH2, vimentin, fibronectin, and MMP2, along with ZEB1. Moreover, ZEB1 silencing abrogated the EMT-enhancing effects of SSEA3-ceramide. CONCLUSIONS: Higher expression of SSEA3 was an independent predictor for RFS and OS in HCC and promoted EMT of HCC via upregulation of ZEB1.

Chemoenzymatic Synthesis of Globo-series Glycosphingolipids and Evaluation of Their Immunosuppressive Activities.

Glycosphingolipids (GSLs) play essential roles in many important biological processes, making them attractive synthetic targets. In this paper, a viable chemoenzymatic method is described for the synthesis of globo-series GSLs, namely, Gb4, Gb5, SSEA-4, and Globo H. The strategy uses a chemically synthesized lactoside acceptor equipped with a partial ceramide structure that is uniquely extended by glycosyltransferases in a highly efficient one-pot multiple enzyme (OPME) procedure. A direct and quantitative conversion of Gb4 sphingosine to Globo H sphingosine is achieved by performing two-sequential OPME glycosylations. A reduction and N-acylation protocol allows facile incorporation of various fatty acids into the lipid portions of the GSLs. The chemically well-defined lipid-modified Globo H-GSLs displayed some differences in their immunosuppressive activities, which may benefit the structural modifications of Globo H ceramides in finding new types of immunosuppressive agents. The strategy outlined in this work should be applicable to the rapid access to other complex GSLs.

Acceptor-mediated regioselective enzyme catalyzed sialylation: chemoenzymatic synthesis of GAA-7 ganglioside glycan.

Herein, we applied PmST1 (a sialyltransferase) to achieve acceptor-mediated regioselective sialylation (AMRS) on the nonreducing end GalNH2 or GalAz (2-azido-2-deoxy galactose). Thus, C5 and C8-modified sialic acid was efficiently assembled on GalNH2 (or GalAz) to achieve the synthesis of the GAA-7 (one of the echinodermatous gangliosides with higher neuritogenic activity) glycan moiety.

Flux synthesis, crystal structures, and luminescence properties of salt-inclusion lanthanide silicates: [K9F2][Ln3Si12O32] (Ln = Sm, Eu, Gd).

New salt-inclusion lanthanide silicates, [K 9F 2][Ln 3Si 12O 32] (Ln = Sm, Eu, Gd), have been synthesized using a KF-MoO 3 flux, and structurally characterized by single-crystal and powder X-ray diffraction. The structures of these three isostructural compounds consist of open-branched funfer silicate single layers with six-, eight-, and twelve-membered rings, which are connected via LnO 6 octahedra to form a 3-D framework. The F (-) and K (+) ions are located in the structural channels and form a F 2K 7 dimer with a structure similar to that of Cl 2O 7. The photoluminescence properties of the Eu compound have also been studied. The sharp peaks in the room-temperature emission spectrum are assigned and the relative intensities of the (5)D 0 --> (7)F 1 and (5)D 0 --> (7)F 2 transitions are consistent with the crystallography results. Crystal data for the Eu compound: triclinic, space group P1 (No. 2), a = 6.8989(2) A, b = 11.3834(4) A, c = 11.4955(4) A, alpha = 87.620(2) degrees , beta = 89.532(2) degrees , gamma = 80.221(2) degrees , and Z = 2. Crystal data for the Sm compound: The same as those for the Eu compound except a = 6.9152(6) A, b = 11.400(1) A, c = 11.531(1) A, alpha = 87.610(1) degrees , beta = 89.445(1) degrees , and gamma = 80.081(1) degrees .

Synthesis, crystal structure, magnetic and luminescence properties of KEuGe2O6: a europium cyclogermanate containing infinite chains of edge-sharing Eu-O polyhedra.

A new Eu(III) germanate, KEuGe2O6, has been synthesized by both the flux-growth method and the high-temperature, high-pressure hydrothermal method and characterized by single-crystal X-ray diffraction. The compound contains parallel zigzag chains of edge-sharing Eu-O polyhedra, which are in turn linked by sharing vertices and edges with three-membered single ring Ge3O9(6-) germanate anions to form a 3-D framework structure. The magnetic and luminescence properties were also investigated. The observed chiMT value at 300 K is 4.53 emu K mol(-1), which is in good agreement with the calculated value for three Eu3+ ions. The sharp peaks in the room-temperature emission spectrum are assigned. The number of lines in the region of the 5D0-->7F0 transition and the relative intensities of the 5D0-->7F1 and 5D0-->7F2 transitions confirm the presence of two local Eu3+ environments and strongly distorted Eu3+-ligand surroundings. The reasons for the very short emission life time is discussed. The Sm and Tb analogues have also been synthesized.

Flux synthesis, crystal structure, and luminescence properties of a new europium fluoride-silicate: K5Eu2FSi4O13.

The crystal structure and luminescence properties of flux-grown crystals of a new europium(III) fluoride-silicate, K5Eu2FSi4O13, are reported. The structure consists of octahedral dimers of the composition [Eu2O10F], which are linked by unbranched tetrasilicate chains to form a 3-D framework with 5- and 6-ring channels parallel to the b axis where the K+ cations are located. The sharp peaks in the room-temperature emission spectrum are assigned. The number of lines in the region for the 5D0-->7F0 transition and the relative intensities of the 5D0-->7F1 and 5D0-->7F2 transitions confirm the presence of two local Eu3+ environments and strongly distorted Eu3+-ligand surroundings. The room-temperature fluorescence decay curves are well fit by a single-exponential function yielding a lifetime value of about 2.0 ms. Crystal data: monoclinic, space group P21/m, a=7.1850(2) A, b=5.7981(2) A, c=18.1675(6) A, beta=92.248(2) degrees , and Z=2.