A unique B cell epitope-based particulate vaccine shows effective suppression of hepatitis B surface antigen in mice.

OBJECTIVE: This study aimed to develop a novel therapeutic vaccine based on a unique B cell epitope and investigate its therapeutic potential against chronic hepatitis B (CHB) in animal models. METHODS: A series of peptides and carrier proteins were evaluated in HBV-tolerant mice to obtain an optimised therapeutic molecule. The immunogenicity, therapeutic efficacy and mechanism of the candidate were investigated systematically. RESULTS: Among the HBsAg-aa119-125-containing peptides evaluated in this study, HBsAg-aa113-135 (SEQ13) exhibited the most striking therapeutic effects. A novel immunoenhanced virus-like particle carrier (CR-T3) derived from the roundleaf bat HBV core antigen (RBHBcAg) was created and used to display SEQ13, forming candidate molecule CR-T3-SEQ13. Multiple copies of SEQ13 displayed on the surface of this particulate antigen promote the induction of a potent anti-HBs antibody response in mice, rabbits and cynomolgus monkeys. Sera and purified polyclonal IgG from the immunised animals neutralised HBV infection in vitro and mediated efficient HBV/hepatitis B virus surface antigen (HBsAg) clearance in the mice. CR-T3-SEQ13-based vaccination induced long-term suppression of HBsAg and HBV DNA in HBV transgenic mice and eradicated the virus completely in hydrodynamic-based HBV carrier mice. The suppressive effects on HBsAg were strongly correlated with the anti-HBs level after vaccination, suggesting that the main mechanism of CR-T3-SEQ13 vaccination therapy was the induction of a SEQ13-specific antibody response that mediated HBV/HBsAg clearance. CONCLUSIONS: The novel particulate protein CR-T3-SEQ13 suppressed HBsAg effectively through induction of a humoural immune response in HBV-tolerant mice. This B cell epitope-based therapeutic vaccine may provide a novel immunotherapeutic agent against chronic HBV infection in humans.

Crystal Structures, Stabilities, Electronic Properties, and Hardness of MoB2: First-Principles Calculations.

On the basis of the first-principles techniques, we perform the structure prediction for MoB2. Accordingly, a new ground-state crystal structure WB2 (P63/mmc, 2 fu/cell) is uncovered. The experimental synthesized rhombohedral R3̅m and hexagonal AlB2, as well as theoretical predicted RuB2 structures, are no longer the most favorite structures. By analyzing the elastic constants, formation enthalpies, and phonon dispersion, we find that the WB2 phase is thermodynamically and mechanically stable. The high bulk modulus B, shear modulus G, low Poisson's ratio ν, and small B/G ratio are benefit to its low compressibility. When the pressure is 10 GPa, a phase transition is observed between the WB2-MoB2 and the rhombohedral R3̅m MoB2 phases. By analyzing the density of states and electron density, we find that the strong covalent is formed in MoB2 compounds, which contributes a great deal to its low compressibility. Furthermore, the low compressibility is also correlated with the local buckled structure.

Structural and relative stabilities, electronic properties, and hardness of iron tetraborides from first prinicples.

First-principles calculations were carried out to investigate the structure, phase stability, electronic property, and roles of metallicity in the hardness for recently synthesized FeB4 with various different structures. Our calculation indicates that the orthorhombic phase with Pnnm symmetry is the most energetically stable one. The other four new dynamically stable phases belong to space groups monoclinic C2/m, orthorhombic Pmmn, trigonal R3̅m, and hexagonal P63/mmc. Their mechanical and thermodynamic stabilities are verified by calculating elastic constants, formation enthalpies, and phonon dispersions. We found that all phases are stabilized further under pressure. Above the pressure of about 50 GPa, the formation enthalpy of Pmmn is almost equal to that of P63/mmc phase. The analysis on density of states not only demonstrates that formation of strong covalent bonding in these compounds contributes greatly to their stabilities but also that they all exhibit metallic behavior which does not relate to the approach used. By considering metallic contributions, the estimated Vickers hardness values based on the semiempirical model show that the OsB4-structured FeB4, with a hardness of 48.1 GPa, well exceeding the limitation of superhardness (40 GPa), is more hard than the most stable phase. The others are predicted to be potential hard materials. Moreover, the atomic configuration and strong B-B covalent bonds are found to play important roles in the hardness of materials.

Phase stability, mechanical properties, hardness, and possible reactive routing of chromium triboride from first-principle investigations.

The first-principles calculations are employed to provide a fundamental understanding of the structural features and relative stability, mechanical and electronic properties, and possible reactive route for chromium triboride. The predicted new phase of CrB3 belongs to the rhombohedral phase with R-3m symmetry and it transforms into a hexagonal phase with P-6m2 symmetry at 64 GPa. The mechanical and thermodynamic stabilities of CrB3 are verified by the calculated elastic constants and formation enthalpies. Also, the full phonon dispersion calculations confirm the dynamic stability of predicted CrB3. Considering the role of metallic contributions, the calculated hardness values from our semiempirical method for rhombohedral and hexagonal phases are 23.8 GPa and 22.1 GPa, respectively. In addition, the large shear moduli, Young's moduli, low Poisson's ratios, and small B∕G ratios indicate that they are potential hard materials. Relative enthalpy calculations with respect to possible constituents are also investigated to assess the prospects for phase formation and an attempt at high-pressure synthesis is suggested to obtain chromium triboride.

Serum neuronal pentraxin 2 is related to cognitive dysfunction and electroencephalogram slow wave/fast wave frequency ratio in epilepsy.

BACKGROUND: Cognitive dysfunction in epileptic patients is a high-incidence complication. Its mechanism is related to nervous system damage during seizures, but there is no effective diagnostic biomarker. Neuronal pentraxin 2 (NPTX2) is thought to play a vital role in neurotransmission and the maintenance of synaptic plasticity. This study explored how serum NPTX2 and electroencephalogram (EEG) slow wave/fast wave frequency ratio relate to cognitive dysfunction in patients with epilepsy. AIM: To determine if serum NPTX2 could serve as a potential biomarker for diagnosing cognitive impairment in epilepsy patients. METHODS: The participants of this study, conducted from January 2020 to December 2021, comprised 74 epilepsy patients with normal cognitive function (normal group), 37 epilepsy patients with cognitive dysfunction [epilepsy patients with cognitive dysfunction (ECD) group] and 30 healthy people (control group). The mini-mental state examination (MMSE) scale was used to evaluate cognitive function. We determined serum NPTX2 levels using an enzyme-linked immunosorbent kit and calculated the signal value of EEG regions according to the EEG recording. Pearson correlation coefficient was used to analyze the correlation between serum NPTX2 and the MMSE score. RESULTS: The serum NPTX2 level in the control group, normal group and ECD group were 240.00 ± 35.06 pg/mL, 235.80 ± 38.01 pg/mL and 193.80 ± 42.72 pg/mL, respectively. The MMSE score was lowest in the ECD group among the three, while no significant difference was observed between the control and normal groups. In epilepsy patients with cognitive dysfunction, NPTX2 level had a positive correlation with the MMSE score (r = 0.367, P = 0.0253) and a negative correlation with epilepsy duration (r = -0.443, P = 0.0061) and the EEG slow wave/fast wave frequency ratio value in the temporal region (r = -0.339, P = 0.039). CONCLUSION: Serum NPTX2 was found to be related to cognitive dysfunction and the EEG slow wave/fast wave frequency ratio in patients with epilepsy. It is thus a potential biomarker for the diagnosis of cognitive impairment in patients with epilepsy.

[Surgical outcome and prognostic factors in focal cortical dysplasia with intractable epilepsy].

OBJECTIVE: To analyze surgical outcome and relevant surgical parameters including resection extent of epileptogenic zone,pathological subtype, brain MRS and MRI results in FCD with intractable epilepsy. METHODS: We retrospectively analyzed surgical outcomes of 35 patients with intractable epilepsy related to focal cortical dysplasia, accepted surgery in the first affiliated hospital of Fujian Medical University from January 2008 to January 2010, with 12-36 months of postoperative follow-up. The relevance between complete resection, pathological subtype, MRS and MRI result and surgical outcome were statistically evaluated. RESULTS: 22 patients (66.7%) were Engel class I, 5 patients (14.3%) were class II, 6 patients (17.2%) were class III, 2 patients (5.8%) were class IV. Complete resection of epileptogenic zone (P < 0.05), FCD type I (P < 0.05) correlated significantly with favorable surgical outcome. Other factors such as MRI results, abnormal NAA/CHO + Cr ratio on the contralateral side of epileptogenic zone, as well as MRS-accurate lateralization did not influence outcome. CONCLUSION: Overall, the surgical outcome of FCD is favorable. Complete resection, FCD type I correlates significantly with favorable surgical outcome.