遷移金属触媒の開発及び空気亜鉛電池と水分解への応用

九州工業大学博士学位論文（要旨）学位記番号：生工博甲第443号 学位授与年月日：令和4年9月26

Effect of Clozapine on Anti-N-Methyl-D-Aspartate Receptor Encephalitis With Psychiatric Symptoms: A Series of Three Cases

The main clinical manifestations of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis are acute or subacute seizures, cognition impairment, and psychiatric symptoms. Nowadays, the scheme of antipsychotic therapy for this disease has not been established. This study reports three cases of anti-NMDAR encephalitis with psychiatric symptoms. The anti-NMDAR antibodies in cerebrospinal fluid (CSF) and serum were positive. The psychiatric symptoms still existed after intravenous immunoglobulin (IVIG) treatment; thus, clozapine was used for antipsychotic therapy. Case 1 was a 37-year-old man who suffered from bad mood and suicide behaviors for 1 month. Hallucination and delusion still existed after IVIG treatment and hormone therapy, and the symptoms were relieved when given clozapine for 12 months. Case 2 was a 28-year-old man who was admitted to our hospital due to injuring other people and destructive behaviors for 2 days. He showed irritability, bad temper, declined cognition, and severe delusion of persecution after IVIG treatment and hormone therapy, but the psychiatric symptoms disappeared when given clozapine for 3 months. Case 3 was a 23-year-old man who suffered from headache and babbing for 7 days. Symptoms such as irritability, bad temper, babbing, and injuring other people still existed after IVIG treatment and hormone therapy, but they disappeared when given clozapine for 2 months. Therefore, we suggest that during the treatment of anti-NMDAR encephalitis with psychiatric symptoms, if the anti-NMDAR antibodies in CSF and serum were positive, and psychiatric symptoms could not be controlled after IVIG and hormone therapy, clozapine may work

Phosphoantigen/IL2 Expansion and Differentiation of Vγ2Vδ2 T Cells Increase Resistance to Tuberculosis in Nonhuman Primates

Dominant Vγ2Vδ2 T-cell subset exist only in primates, and recognize phosphoantigen from selected pathogens including M. tuberculosis(Mtb). In vivo function of Vγ2Vδ2 T cells in tuberculosis remains unknown. We conducted mechanistic studies to determine whether earlier expansion/differentiation of Vγ2Vδ2 T cells during Mtb infection could increase immune resistance to tuberculosis in macaques. Phosphoantigen/IL-2 administration specifically induced major expansion and pulmonary trafficking/accumulation of phosphoantigen-specific Vγ2Vδ2 T cells, significantly reduced Mtb burdens and attenuated tuberculosis lesions in lung tissues compared to saline/BSA or IL-2 controls. Expanded Vγ2Vδ2 T cells differentiated into multifunctional effector subpopulations capable of producing anti-TB cytokines IFNγ, perforin and granulysin, and co-producing perforin/granulysin in lung tissue. Mechanistically, perforin/granulysin-producing Vγ2Vδ2 T cells limited intracellular Mtb growth, and macaque granulysin had Mtb-bactericidal effect, and inhibited intracellular Mtb in presence of perforin. Furthermore, phosphoantigen/IL2-expanded Vγ2Vδ2 T effector cells produced IL-12, and their expansion/differentiation led to enhanced pulmonary responses of peptide-specific CD4+/CD8+ Th1-like cells. These results provide first in vivo evidence implicating that early expansion/differentiation of Vγ2Vδ2 T effector cells during Mtb infection increases resistance to tuberculosis. Thus, data support a rationale for conducting further studies of the γδ T-cell-targeted treatment of established TB, which might ultimately help explore single or adjunctive phosphoantigen expansion of Vγ2Vδ2 T-cell subset as intervention of MDR-tuberculosis or HIV-related tuberculosis

A Novel RNF139 Mutation in Hemangioblastomas: Case Report

Hemangioblastomas (HBs) are classified as grade I tumors with uncertain origin according to the World Health Organization's classification system. HBs are characterized by rich mesenchymal cells and abundant capillaries. It has been shown that tumorigenesis of HBs depends on mutational inactivation of Von Hippel-Lindau (VHL) tumor suppressor gene. Therefore, the majority of patients will undergo VHL single gene test, and sequencing scheme is rarely used in clinic. In this study, we described a girl and her father successively found to have HBs within half a year. The results of next-generation sequencing (NGS) and Sanger sequencing analysis showed that both of them carried heterozygous mutation of RNF139 p.Q650R. This mutation was interpreted as Pathogenic variation based on the American College of Medical Genetics and Genomics (ACMG) guideline. Sanger sequencing was performed with other family members. No mutation on rs118184842 locus of RNF139 gene was found in the samples from the girl's mother, uncle and aunt. This report supports that the novel mutation of RNF139 p.Q650R probably serve as a key role in HBs progression

DR*W201/P65 Tetramer Visualization of Epitope-Specific CD4 T-Cell during M. tuberculosis Infection and Its Resting Memory Pool after BCG Vaccination

In vivo kinetics and frequencies of epitope-specific CD4 T cells in lymphoid compartments during M. tuberculosis infection and their resting memory pool after BCG vaccination remain unknown.Macaque DR*W201 tetramer loaded with Ag85B peptide 65 was developed to directly measure epitope-specific CD4 T cells in blood and tissues form macaques after M. tuberculosis infection or BCG vaccination via direct staining and tetramer-enriched approach. The tetramer-based enrichment approach showed that P65 epitope-specific CD4 T cells emerged at mean frequencies of approximately 500 and approximately 4500 per 10(7) PBL at days 28 and 42, respectively, and at day 63 increased further to approximately 22,000/10(7) PBL after M. tuberculosis infection. Direct tetramer staining showed that the tetramer-bound P65-specific T cells constituted about 0.2-0.3% of CD4 T cells in PBL, lymph nodes, spleens, and lungs at day 63 post-infection. 10-fold expansion of these tetramer-bound epitope-specific CD4 T cells was seen after the P65 peptide stimulation of PBL and tissue lymphocytes. The tetramer-based enrichment approach detected BCG-elicited resting memory P65-specific CD4 T cells at a mean frequency of 2,700 per 10(7) PBL.Our work represents the first elucidation of in vivo kinetics and frequencies for tetramer-bound epitope-specific CD4 T cells in the blood, lymphoid tissues and lungs over times after M. tuberculosis infection, and BCG immunization

Development of Transition Metal Catalysts and Application to Zinc-Air Battery and Water Splitting

1. Introduction||2. Synthesis of one-dimensional vanadium-doped CoS/Co9S8 heterojunctions as bifunctional electrocatalysts for zinc-air battery||3. Facile approach to synthesize high entropy alloy for zinc-air battery and methanol upgrading reaction||4. Facile approach to Synthesize High entropy alloy for Bifunctional Catalysis toward HER, OER and Water SplittingOxygen evolution reaction (OER), oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER) are important reactions in energy storage and conversion devices such as zinc-air battery and water splitting. However, the sluggish dynamics of the OER, ORR and HER decrease the final energy, which limits the commercialization of these devices. Besides, the traditional Ir/Ru and Pt-based catalysts limit their wide application due to their high price and rare reserves. This thesis focuses on designing efficient transition metal electrochemical catalysts. Firstly, the vanadium doped CoS/Co9S8 heterostructures embedded on carbon nanorods (denoted as V-CoS/Co9S8@CNR) was synthesized. The results verified that vanadium doping and interface effect were beneficial to the OER and ORR performance. Secondly, to further improve the catalytic activity, four kinds of high entropy alloys (HEAs) were synthesized. The obtained catalysts were used as the bifunctional electrocatalysts for OER and ORR. Thirdly, these alloys were applied to overall water splitting, the MnFeRuCoNiZn had a lower potential than the traditional catalyst of RuO2+Pt/C. In Chapter 1, the background and development history of OER, ORR and HER were introduced. In addition, the structure of zinc-air battery and water splitting were also described in detail. Moreover, the current challenges and the purpose of this thesis were also described. In Chapter 2, the vanadium doped CoS/Co9S8 heterostructure embedded on carbon nanorods were synthesized by a facile one-step sulfurization strategy, which was used as the OER and ORR electrocatalysts for ZABs in an alkaline medium. The obtained V-CoS/Co9S8@CNR showed an excellent OER catalytic performance (269 mV@10 mA/cm2) and comparable ORR catalytic performance. The assembled rechargeable zinc-air batteries displayed a superior performance as well as high charging-discharging cycling stability. In Chapter 3, to further improve the catalytic performance, four kinds of senary high entropy alloys (HEAs) were synthesized by a MOF-assisted strategy. Among the synthesized high entropy alloys, MnFeRuCoNiZn showed the best excellent OER catalytic performance (240 mV@10 m/cm2). Using MnFeRuCoNiZn as the air electrode catalyst for zinc-air battery, the assembled zinc-air battery showed good catalytic performance. In Chapter 4, to further understand the relationship between catalytic performance and the metal number, a series of multi-component alloys were synthesized. Among the synthesized alloys, the senary MnFeRuCoNiZn alloys showed best HER performance. Besides, for overall water splitting, MnFeRuCoNiZn alloys showed better performance than the standard RuO2+Pt/C. Finally, the general conclusions of this thesis were summarized. In this thesis, the as-prepared 3 kinds of materials exhibited good electrochemical performance in ZABs or water splitting. It would have great significance to further study the preparation of economy and efficient catalysts.九州工業大学博士学位論文 学位記番号：生工博甲第443号 学位授与年月日：令和4年9月26日令和4年

Operation method of allowing variation interval of downstream water level in the middle route of South-to-North Water Diversion Project

To realize demand-oriented operations in the middle route of South-to-North Water Diversion Project, this paper proposed a pool operation method that a variation interval of water level at the upstream of the check gate is allowed. In this method, water users’ demand for flow changes can be satisfied as much as possible. Accordingly, downstream water depth is kept to fluctuate within a certain range, which is determined considering the canal safety, the operation frequency of check gates and the pool delay. The method is tested using the self-developed simulation platform for the middle route of South-to-North Water Diversion Project, which is established based on the Saint-Venant equations and programmed with the language Fortran. Results show that the flow changes demanded by water users, either increase or decrease, can be achieved effectively, while the water level variations can meet the restrictions for canal operation safety, and the frequency of gate adjustment is practically acceptable as well. Therefore, the operation method of allowing variation interval of downstream water level is suitable in the middle route of South-to-North Water Diversion Project at the current stage