Heterocyclic Ligands with Different N/O Donor Modes for Am(III)/Eu(III) Separation: A Theoretical Perspective.

Excellent "CHON" compatible ligands based on a heterocyclic skeleton for the separation of trivalent actinides [An(III)] from lanthanides [Ln(III)] have been widely explored, the aim being spent nuclear fuel reprocessing. The combination mode of a soft/hard (N/O) donor upon the coordination chemistry of An(III) and Ln(III) should play a vital role with respect to the performance of ligands. As such, in this work, two typical experimentally available phenanthroline-derived tetradentate ligands, CyMe4-BTPhen (L1) and Et-Tol-DAPhen (L4), and two theoretically designed asymmetric tetradentate heterocyclic ligands, L2 and L3, with various N/O donors were investigated using scalar relativistic density functional theory. We have evaluated the electronic structures of L1-L4 and their coordination modes, bonding properties, and extraction reactions with Am(III) and Eu(III). We found that the Am/Eu-N interactions play a more important role in the orbital interactions between the ligand and Am(III)/Eu(III) ions. Compared with those of L1, the coordinated O atoms of L2 and L4 weaken the metal-N bonds. The Am(III)/Eu(III) selectivity follows the order L1 > L2 > L4 based on the change in Gibbs free energy, reflecting the fact that the Am(III)/Eu(III) selectivity of the ligand is affected by the number of coordinated N atoms. In addition, L3 displays the strongest binding ability for Am(III)/Eu(III) ions and the smallest Am(III)/Eu(III) selectivity among the four ligands, due to its structural preorganization. This work clarifies the influence of the number of coordinated N and O atoms of ligands on Am(III)/Eu(III) selectivity, which provides valuable fundamental information for the design of efficient ligands with N and O donors for An(III)/Ln(III) separation.

Optimized GAPDH-truncated immunogen of Streptococcus equi elicits an enhanced immune response and provides effective protection in a mouse model.

Strangles is an acute and frequently diagnosed infectious disease caused by Streptococcus equi subsp. equi. Infection with this pathogen can cause grave losses to the equine industry. The present work investigates glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an important surface-localized virulence factor of S. equi, to determine whether it could be developed into an efficacious and suitable subunit vaccine against strangles. Two different recombinant fragments of S. equi GAPDH, namely, GAPDH-L and GAPDH-S, were constructed and expressed. Further, the antigenicity and immunogenicity of these two recombinant proteins were compared and evaluated in a mouse model. Our results revealed that immune responses were efficiently induced by the proteins in immunized mice. Remarkably, higher survival rates and significantly lower bacterial loads in the lung, liver, kidney, and spleen were observed in the GAPDH-S group compared with the GAPDH-L group after challenge with S. equi. High levels of specific antibodies, elevated antibody titers, and increased proportions of CD8 + T cells further indicated that GAPDH-S elicited better humoral and cellular immune responses than GAPDH-L. Furthermore, the induction of TCR, TLR-2, TLR-3, and TLR-4 significantly increased in the GAPDH-S group compared with those in the GAPDH-L and negative control groups. In summary, our results indicate that the optimized recombinant protein GAPDH-S is a promising candidate construct that may be further developed into a multivalent subunit vaccine for strangles.

[Expressions of MMP-7 and TIMP-1 in Chronic Stomach Disease Patients with Different Syndromes of Chinese Medicine].

Objective To observe the expressions of matrix metalloproteinase-7 (MMP-7) and tissue inhibitor of metalloproteinase-1 (TIMP-1 ) in chronic stomach disease patients with different syn- dromes of Chinese medicine (CM) , and their relationships with Helicobacter pylori ( Hp ) infection. Meth- ods Totally 117 chronic stomach disease patients were recruited, and 11 healthy volunteers were also recruited. Chronic stomach disease patients were assigned to Pi-Wei dampness-heat syndrome (PWDHS, 57 cases) , disharmony of Gan and Wei syndrome (DGWS, 30 cases) , and Pi qi deficiency syndrome (PQDS, 30 cases) by syndrome typing. Healthy volunteers were recruited as the healthy con- trol group. Hp infection was detected using methylene blue dyeing and rapid urease test (RUT). The degree of inflammation was observed by conventional HE staining. The protein expressions of MMP-7 and TIMP-1 were detected qualitatively and positioningly using immunohistochemical method. Results Patients with PWDHS and patients with DGWS had equivalent Hp infection rate and degree. They showed a slightly increasing tendency than patients with PQDS, but with no statistical difference (P >0. 05). Com- pared with PWDHS and PQDS groups, more severe inflammation of mucosa occurred in patients with DG- WS (P <0. 05). More severe inflammation of mucosa occurred in patients with PWDHS than in those with PQDS, but with no statistical difference (P >0. 05). The severity of gastric mucosal inflammatory activity was sequenced from high to low as PWDHS, DGWS, PQDS, all with statistical difference (P <0. 05). Compared with Hp negative patients, the gastric mucosal inflammatory activity was more severe in Hp positive patients with PWDHS, DGWS, PQDS. The gastric mucosal inflammatory activity was more se- vere in Hp positive patients with PWDHS and PQDS (P <0. 05). Compared with the healthy control group, the expression level of TIMP-1 in gastric mucosa increased in patients with PWDHS, DGWS, PQDS (P <0. 05, P <0. 01) ; the expression level of MMP-7 increased in Hp negative patients with PWDHS (P < 0. 05). Compared with Hp negative patients with PWDHS, the expression level of MMP-7 decreased in Hp positive patients with PWDHS (P <0. 05). Compared with the PQDS group, the expression level of TIMP-1 decreased in the PWDHS group (P <0. 01). The severity of gastric mucosal inflammation was negatively correlated with the expression level of MMP-7, and positively correlated with the expression level of TIMP- 1 (P <0. 01). Hp infection degree was not obviously correlated with the expression level of MMP-7 in gastric mucosa (P >0. 05) , but positively correlated with the expression level of TIMP-1 in gastric mucosa (P <0. 05). Of them, the expression level of MMP-7 in gastric mucosa was positively correlated with the expression level of TIMP-1 in gastric mucosa (P <0. 01). Conclusions Comparatively lower expression of MMP-7 in gastric mucosal inflammation and imbalanced expression of TIMP-1 might be two of the pathogeneses of chronic stomach disease. Their various expressions in different CM syndromes might have certain expositions for microscopic research on "different syndromes of the same disease". Emotional fluctuation might also be one of important factors for chronic stomach disease.