Development and properties of multifunctional biomedical nanocomposites（多機能生体医療用ナノコンポジットの創成およびその特性に関する研究）

信州大学(Shinshu university)博士（工学)ThesisYU JUHONG. Development and properties of multifunctional biomedical nanocomposites（多機能生体医療用ナノコンポジットの創成およびその特性に関する研究）. 信州大学, 2018, 博士論文. 博士（工学), 甲第680号, 平成30年03月20日授与.doctoral thesi

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor–related pneumonitis

BackgroundCheckpoint inhibitor–related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined.MethodsWe conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase’s characteristics.ResultsThere were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P<0.05). The main change in radiologic features was the absorption of the lesions, and 3 (3/11) patients in the chronic phase had persistent traction bronchiectasis. For histologic features, most patients had acute fibrinous pneumonitis in the acute phase (5/8), and most had organizing pneumonia in the subacute phase (5/6). Other histologic changes advanced over time, with the lesions entering a state of fibrosis. Moreover, the levels of interleukin-6, interleukin-10 and high-sensitivity C-reactive protein (hsCRP) increased in the acute phase and decreased as CIP progressed (IL-6: 17.9 vs. 9.8 vs. 5.7, P=0.018; IL-10: 4.6 vs 3.0 vs. 2.0, P=0.041; hsCRP: 88.2 vs. 19.4 vs. 14.4, P=0.005).ConclusionsThe general development process of CIP can be divided into acute, subacute, and chronic phases, upon which a better management strategy might be based devised

Effects of statins on cytokines levels in gingival crevicular fluid and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus.

ObjectiveTo analyze the effect of statins on cytokines levels in gingival crevicular fluid (GCF) and saliva and on clinical periodontal parameters of middle-aged and elderly patients with type 2 diabetes mellitus (T2DM).MethodsSystemically healthy controls (C group, n = 62), T2DM patients not taking statins (D group, n = 57) and T2DM patients taking statins (S group, n = 24) were recruited. In each group, subjects (40-85 years) were subclassified into the h (periodontal health)group, the g (gingivitis)group or the p (periodontitis) group according to different periodontal conditions. 17 cytokines in gingival crevicular fluid (GCF) and saliva samples of each subject were measured utilizing the Luminex technology kit. Further, HbA1c (glycated hemoglobin), FPG (fasting plasma glucose), PD (probing depth), CAL (clinical attachment level), BOP (bleeding on probing), GI (gingival index) and PI (periodontal index) were recorded. Data distribution was tested through the Shapiro-Wilk test, upon which the Kruskal-Wallis test was applied followed by Mann-Whitney U test and Bonferroni's correction.ResultsLevels of IFN-γ, IL-5, IL-10 and IL-13 in the saliva of the Dh group were significantly lower than those in the Ch group, while factor IL-4 was higher (pConclusionStatins are associated with reduced PD and cytokines levels in the GCF and saliva of T2DM patients with periodontitis

Phage Predation Promotes Filamentous Bacterium <i>Piscinibacter</i> Colonization and Improves Structural and Hydraulic Stability of Microbial Aggregates

Although bacteria–phage interactions have broad environmental applications and ecological implications, the influence of phage predation on bacterial aggregation and structural stability remains largely unexplored. Herein, we demonstrate that inefficient lytic phage predation can promote host filamentous bacterium Piscinibacter colonization onto non-host Thauera aggregates, improving the structural and hydraulic stability of the dual-species aggregates. Specifically, phage predation at 103–104 PFU/mL (i.e., multiplication of infection at 0.01–0.1) promoted initial Piscinibacter colonization by 10–15 folds and resulted in 29–31% higher abundance of Piscinibacter in the stabilized aggregates than that in the control aggregates without phage predation. Transcriptomic analysis revealed upregulated genes related to quorum sensing (by 15–92 folds) and polysaccharide secretion (by 10–90 folds) within the treated aggregates, which was consistent with 120–172% higher content of polysaccharides for the treated dual-species aggregates. Confocal laser scanning microscopic images further confirmed the increase of filamentous bacteria and polysaccharides (both with wider distribution) within the dual-species aggregates. Accordlingly, the aggregates’ structural strength (via atomic force microscopes) and shear resistance (via hydraulic stress tests) increased by 77 and 42%, respectively, relative to the control group. In the long-term experiments, the enhanced hydraulic stability of the treated aggregates could facilitate dwelling bacteria propagation in flow-through conditions. Overall, our study demonstrates that phage predation can promote bacterial aggregation and enhance aggregate structural stability, revealing the beneficial role of lytic phage predation on bacterial symbiosis and environmental adaptivity

Purification and Functional Characterization of a Soluble Trehalase in <i>Lissorhoptrus oryzophilus</i> (Coleoptera: Curculionidae)

Trehalase is the only enzyme known for the irreversible splitting of trehalose and plays a major role in insect growth and development. In this report, we describe a basic study of the trehalase gene fragment encoding a soluble trehalase from Lissorhoptrus oryzophilus (LoTRE1). Sequence alignment and phylogenetic analysis suggested that LoTRE1 was similar to some known insect trehalases and belongs to the Coleoptera trehalase group. Additionally, LoTRE1 was expressed mainly in the fat body. Purified protein was obtained using heterologous expression of LoTRE1 in Escherichia coli, and the recombinant protein exhibited the ability to decompose trehalose. Enzyme–substrate docking indicated the potential involvement of other residues in the catalytic activity, in addition to Asp 333. Moreover, feeding of adults on LoTRE1 dsRNA silenced the transcription of LoTRE1 and thereby reduced the activity of trehalase and increased the trehalose content; it also led to a 12% death rate. This study reveals essential molecular features of trehalase and offers insights into the structural aspects of this enzyme, which might be related to its function. Taken together, the findings demonstrate that LoTRE1 is indispensable for adults of this pest and provide a new target for the control of L. oryzophilus

The association of prokaryotic antiviral systems and symbiotic phage communities in drinking water microbiomes

Abstract Prokaryotic antiviral systems are important mediators for prokaryote-phage interactions, which have significant implications for the survival of prokaryotic community. However, the prokaryotic antiviral systems under environmental stress are poorly understood, limiting the understanding of microbial adaptability. Here, we systematically investigated the profile of the prokaryotic antiviral systems at the community level and prokaryote-phage interactions in the drinking water microbiome. Chlorine disinfectant was revealed as the main ecological driver for the difference in prokaryotic antiviral systems and prokaryote-phage interactions. Specifically, the prokaryotic antiviral systems in the microbiome exhibited a higher abundance, broader antiviral spectrum, and lower metabolic burden under disinfectant stress. Moreover, significant positive correlations were observed between phage lysogenicity and enrichment of antiviral systems (e.g., Type IIG and IV restriction-modification (RM) systems, and Type II CRISPR-Cas system) in the presence of disinfection, indicating these antiviral systems might be more compatible with lysogenic phages and prophages. Accordingly, there was a stronger prokaryote-phage symbiosis in disinfected microbiome, and the symbiotic phages carried more auxiliary metabolic genes (AMGs) related to prokaryotic adaptability as well as antiviral systems, which might further enhance prokaryote survival in drinking water distribution systems. Overall, this study demonstrates that the prokaryotic antiviral systems had a close association with their symbiotic phages, which provides novel insights into prokaryote-phage interactions and microbial environmental adaptation

The Effect of Dietary Supplementation with Resveratrol on Growth Performance, Carcass and Meat Quality, Blood Lipid Levels and Ruminal Microbiota in Fattening Goats

This study investigated the effects of resveratrol (RES) supplementation on the growth performance, carcass and meat quality, blood lipid levels and ruminal bacterial microbiota of fattening goats. A total of forty castrated Nubian goats (28.25 &plusmn; 0.26 kg body weight) were randomly divided into four groups and provided with diets containing different levels of RES (0, 150, 300 and 600 mg/kg) for 120 d. The results showed that RES increased redness and intramuscular fat content, whilst reducing shear force in the longissimus dorsi muscle of goats (p &lt; 0.05). In addition, the final weight, average daily gain, hot carcass weight, net meat weight, carcass lean percentage and eye muscle area of goats were significantly increased in the 150 mg/kg RES group compared with the other three groups, while those in the 600 mg/kg RES group significantly decreased (p &lt; 0.05). RES significantly decreased serum triacylglycerol and LDL-C contents (p &lt; 0.05), and increased HDL-C content and the HDL-C/TC ratio (p &lt; 0.05). Supplementation with 150 mg/kg RES also increased the proportion of Acetitomaculum and Moryella, genera comprising short-chain fatty acid-producing bacteria. The present study indicated that an appropriate supplemental level of RES could improve the growth performance, neat percentage, meat quality, ruminal microbiota and serum lipid levels of fattening goats

3D-Printed Porous GO Framework Enabling Dendrite-Free Lithium-Metal Anodes

Although lithium-metal anode is regarded as the most promising candidate for high-energy-density batteries, the uncontrollable Li dendrite growth and large volumetric change have severely inhibited its practical application. Herein, a three-dimensional (3D)-printed graphene oxide framework was constructed as a lithium-metal host to modulate the plating behavior of Li+ on the interfaces. Owing to the specially designed architecture, the 3D-printed GO framework can effectively reduce the local current density and supply large space for the accommodation of Li to buffer the volume change. As a result, the 3D-GO@Li anode enables a dendrite-free Li plating/stripping with a small overpotential of 9 mV and a long-term cycling stability of 1600 h at 1 mA cm–2. Moreover, the stable 3D-GO@Li anode is further corroborated via a full battery with a LiFePO4 cathode with a superior long cycle lifespan and capacity retention in comparison to the pristine Li anode. This work would pave a promising way for 3D printing technology to construct high-energy-density energy storage devices

3D-Printed Porous GO Framework Enabling Dendrite-Free Lithium-Metal Anodes

Although lithium-metal anode is regarded as the most promising candidate for high-energy-density batteries, the uncontrollable Li dendrite growth and large volumetric change have severely inhibited its practical application. Herein, a three-dimensional (3D)-printed graphene oxide framework was constructed as a lithium-metal host to modulate the plating behavior of Li+ on the interfaces. Owing to the specially designed architecture, the 3D-printed GO framework can effectively reduce the local current density and supply large space for the accommodation of Li to buffer the volume change. As a result, the 3D-GO@Li anode enables a dendrite-free Li plating/stripping with a small overpotential of 9 mV and a long-term cycling stability of 1600 h at 1 mA cm–2. Moreover, the stable 3D-GO@Li anode is further corroborated via a full battery with a LiFePO4 cathode with a superior long cycle lifespan and capacity retention in comparison to the pristine Li anode. This work would pave a promising way for 3D printing technology to construct high-energy-density energy storage devices