Type 2 diabetes mellitus (T2

)-associated mitochondrial impairment may a key factor leading to liver injury. Transient receptor potential receptor vanilloid 1 (TRPV1) regulates the energy expenditure and cholesterol metabolism in hepatocytes and protects against oxidative toxicity. Optic atrophy 1 (OPA1) is involved in the protection of TRPV1 on cardiac microvascular and lung injury. The aim of this study is to identify the role of TRPV1 in redox signals and liver protection via OPA1. TRPV1 knockout (TRPV1^-/-) mice were used. And T2 associated liver injury was induced by high glucose and high fatty acid (HG/HF) treatment. Mechanisms were studied by TUNEL staining, transmission electron microscope (TEM) analysis, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting in vivo and in vitro. We determined that HG/HF treatment increased TRPV1 expression in liver tissues and AML12 cells. The knockout of TRPV1 increased the apoptotic hepatocytes rate. The inhibition of TRPV1 by 5'-iRTX in HG/HF group elevated the reactive oxygen species (ROS) levels, whereas TRPV1 agonist capsaicin reduced ROS. Our studies also showed that the OPA1 expression was lower in livers from HG/HF treated mice than the control, and genetic ablation of TRPV1 decreased OPA1 expression to a greater extent than the HG/HF mice. The protective effects of TRPV1 on mitochondrial were blocked by OPA1 siRNA. In conclusion, our study showed that the identified regulation of TRPV1 to OPA1 has important implication to the pathogenesis of T2-associated liver injury. Targeting the action of TRPV1 and OPA1 presents a potential therapeutic intervention.

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Aim: Immunologic dysfunction was recently found to be one of the most important mechanisms underlying the initiation and development of atherosclerosis. Thymus involution can contribute to immune disturbance and disequilibrium of T-cell subsets. This study aimed to explore whether recent thymic emigration (RTE) is impaired in patients with coronary artery disease (CAD).
Methods: Content of signal-joint T cell receptor excision circles (sj-TREC) in T lymphocytes, a molecular marker of RTE, was assessed among CAD patients and age-matched controls. Monochrome multiplex quantitative PCR method was used to assess the samples' telomere length in order to exclude the potential influence of T cell proliferation on the dilution of sj-TREC. Patients were grouped according to Gensini score (GS) (low, GS ＜18; intermediate, GS 18–41; high, GS ＞41). Ordinary logistic regression models were used to determine potential risk factors for CAD and GS tertiles.
Results: Average copy numbers of sj-TREC per 10⁶ T lymphocytes among patients with unstable angina, stable angina, and controls were 726±429, 1213±465, and 1795±838, respectively (P＜0.001). However, there was no significant difference in telomere length among groups. Moreover, the content of sj-TREC in the high GS group was most significantly reduced than the low GS group (P＜0.001). Multivariate logistic regression analysis revealed that lower sj-TREC was independently associated with the progression of CAD (OR=0.44, P＜0.001) and higher GS (OR=0.4, P＜0.001).
Conclusion: Impaired RTE could be partly responsible for CAD development. Mechanisms may be involved in the disturbance of T lymphocyte compartment and interruption of maintained immune tolerance resulting from thymus involution.

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Insufficient bone mass is still a difficult point to be solved in oral implantation, so new bone graft materials are continuously researched and discussed in clinical practice in order to obtain better bone augmentation. In order to explore whether platelet-rich fibrin (PRF) can promote the formation of new bone in mineralized collagen (MC), MC/PRF and pure MC were implanted into the bilateral mandibular defect model in rabbits, respectively. Micro-CT scan and histological evaluation of the target area at 4, 8, and 12 weeks after operation. The results of Micro-CT three-dimensional reconstruction analysis showed that the ratio of bone volume to total volume (BV/TV), trabecular bone number (Tb.N), trabecular bone thickness (Tb.Th) and trabecular bone separation (Tb.Sp) and residual material volume fraction (RMVF) in the MC/PRF group were better than those in the MC group (p<0.05). The results of HE and Masson staining showed that the new bone formation and material degradation rate of the MC/PRF group were better than those of the MC group. The results suggest that PRF can accelerate the formation of new bone in MC, and provide new ideas for the clinical application of new bone graft materials.

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Biological rhythms can be entrained by internal oscillatory processes and often become synchronized with each other. For integrated physiological systems, there is evidence to show that coupling can exist between cardiorespiratory and locomotor systems. Phase synchronization, which has been well documented in articles describing cardiac and locomotor rhythms for individuals engaged in rhythmic activity such as walking, running, or cycling, is called “cardiolocomotor synchronization” or “cardiolocomotor coupling”. Although this coupling has been hypothesized to play a functional role during exercise, the nature of this interaction, its physiological relevance, and the underlying mechanism behind this phenomenon are not fully understood. This review summarizes research findings to date on cardiolocomotor synchronization, and aims to provide the method for identification of phase synchronization between cardiac and locomotor rhythms. In addition, the mechanisms responsible for the synchronization and possible physiological function of this interaction are discussed.

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A relationship between type 2 diabetes mellitus (T2

) and intestinal flora has been suggested since development of analysis technology for intestinal flora. An animal model of T2 is important for investigation of T2. Although there are some animal models of T2, a comparison of the intestinal flora of healthy animals with that of T2 animals has not yet been reported. The intestinal flora of Tsumura Suzuki Obese Diabetes (TSOD) mice was compared with that of Tsumura, Suzuki, Non Obesity (TSNO) mice in the present study. The TSOD mice showed typical type 2 diabetes symptoms, which were high-fat diet-independent. The TSOD and the TSNO mouse models were derived from the same strain, ddY. In this study, we compared the intestinal flora of TSOD mice with that if TSNO mice at 5 and 12 weeks of age. We determined that that the number of operational taxonomic units (OTUs) was significantly higher in the cecum of TSOD mice than in that of TSNO mice. The intestinal flora of the cecum and that of the feces were similar between the TSNO and the TSOD strains. The dominant bacteria in the cecum and feces were of the phyla Firmicutes and Bacteroidetes. However, the content of some bacterial species varied between the two strains. The percentage of Lactobacillus spp. within the general intestinal flora was higher in TSOD mice than in TSNO mice. In contrast, the percentages of order Bacteroidales and family Lachnospiraceae were higher in TSNO mice than in TSOD mice. Some species were observed only in TSOD mice, such as genera Turicibacter and SMB53 (family Clostridiaceae), the percentage of which were 3.8% and 2.0%, respectively. Although further analysis of the metabolism of the individual bacteria in the intestinal flora is essential, genera Turicibacter and SMB53 may be important for the abnormal metabolism of type 2 diabetes.

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With the increasing availability of curative surgical techniques for primary and secondary hepatic neoplasms, the tasks for clinical imaging of liver cancer suspects have become more exacting. Detection of tumor, differential diagnosis of individual nodules, and mapping the anatomic extensions of malignant disease are now routinely required. Related and unrelated liver substrate abnormalities such as cavernous hemangioma and focal fatty deposits are often discovered in liver cancer suspects and must be differentiated from metastatic deposits. Moreover, modern imaging methods frquently display tiny sub-centimeter nodules which often prove difficult to adequately characterize (micrometastases vs other). The most sensitive imaging techniques are CT after arterial portography and intraoperative ultrasound, but because of their invasiveness, these are reserved exclusively for staging. For primary screening MR imaging is increasingly preferred over CT because of its superiority in discriminating hemangiomas and cysts from metastases without the need for iodinated contrast material.

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20 世紀中期から集約的畜産業が急速に発達すると，農用動物の福祉問題が関心を集め，「5 つの自由」と呼ばれる福祉指針が動物行動学や生理学の研究成果を踏まえて確立された．「5 つの自由」は現在，農用動物に限らず愛玩・伴侶動物，実験動物，さらに動物園等の展示動物といった人の管理下にある飼育動物一般に共通の福祉指針として国際的に普及している．本総説では，初めに「5 つの自由」の成立ならびに普及の経緯を述べ，次いで動物の家畜化に際して行われる繁殖管理ならびに育種に起因する動物の健康問題について述べた．最後に，近年グローバル化が進行する中で牛海綿状脳症，口蹄疫，高病原性鳥インフルエンザなどの悪性伝染病が日本で発生し，動物の健康のみならず，人の健康，畜産食品の安全性，および国民経済にとって大きな脅威となっていることを踏まえ，予防獣医学的観点からいくつかの重要な感染症について述べた．

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[Purpose] The aim of this study was to examine the effect of chest expansion resistance exercises (CERE) on chest expansion, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) in elderly people with inspiratory muscle weakness. [Subjects] Thirty elderly people with inspiratory muscle weakness (MIP < 80% of the predicted value) were randomly and equally assigned to a chest expansion resistance exercise (CERE) group, core conditioning exercise (CCE) group, and control group. [Methods] The intervention was applied to the CERE group and CCE group five times per week, 30 minutes each time, for six weeks. A tapeline was used to measure upper and lower chest expansion. MIP and MEP before and after the intervention were measured and compared. [Results] There was significant improvement in upper and lower chest expansion and MIP after the intervention in both the CERE group and the CCE group, whereas the control group did not show any significant difference. MEP did not significantly change in any of the three groups after the intervention. [Conclusion] The CERE group underwent greater changes than the CCE group, which proves that the CERE is more effective for improving elderly people’s chest expansion capacity and MIP in elderly people. Therefore, application of the CERE by therapists is recommended if the environment and conditions are appropriate for enhancement of chest expansion capacity and MIP in elderly people.

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Clinical reports suggest that women may be more prone to develop drug-related QT prolongation and torsades de pointes (TdP) . Lengthening of the QT interval reflects prolonged cardiac repolarization, in which the delayed outward K+ current (Ik) plays a major role. The aim of this study was to investigate the effect of 17 β-estradiol (Es) on Ik using a whole-cell voltage clamp. In isolated guinea pig ventricular myocytes, 10μ mol/L Es decreased Ik.tail elicited by a 5000-msec depolarization, where a slowly activating component of Ik (Iks) dominates (current density using + 50 mV depolariza-tion: control 7.1±2.8vs. Es 5.1±2.0 pA/pF, P<0.05, n=10) . In contrast, 1μ mol/L Es significantly increased Ik.tail elicited by a 250-msec depolariza-tion from -10 to +10 mV (at 0 mV: control 0.68±0.24 vs. Es 0.92±0.24 pA/pF, P<0.05, n=8) . This increase was eliminated by E-4031, suggesting that this increase specifically represents the rapidly activating component of Ik (Ikr) . Es has an acute dose-dependent effect on Ik, and has an opposite effect on Iks and Ikr. These effects may contribute to drug-related QT prolongation and the susceptibility to TdP in women.

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Next-generation sequencing of the V1–V2 and V3 variable regions of the 16S rRNA gene generated a total of 674,116 reads that described six distinct bacterial biofilm communities from both water meters and pipes. A high degree of reproducibility was demonstrated for the experimental and analytical work-flow by analyzing the communities present in parallel water meters, the rare occurrence of biological replicates within a working drinking water distribution system. The communities observed in water meters from households that did not complain about their drinking water were defined by sequences representing Proteobacteria (82–87%), with 22–40% of all sequences being classified as Sphingomonadaceae. However, a water meter biofilm community from a household with consumer reports of red water and flowing water containing elevated levels of iron and manganese had fewer sequences representing Proteobacteria (44%); only 0.6% of all sequences were classified as Sphingomonadaceae; and, in contrast to the other water meter communities, markedly more sequences represented Nitrospira and Pedomicrobium. The biofilm communities in pipes were distinct from those in water meters, and contained sequences that were identified as Mycobacterium, Nocardia, Desulfovibrio, and Sulfuricurvum. The approach employed in the present study resolved the bacterial diversity present in these biofilm communities as well as the differences that occurred in biofilms within a single distribution system, and suggests that next-generation sequencing of 16S rRNA amplicons can show changes in bacterial biofilm communities associated with different water qualities.

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Nitric oxide (NO) may act as either a pro-oxidant or an antioxidant in biological systems. Previous work has found inhalation of NO improved survival in a high altitude rat model. NO donor isosorbide mononitrate derivants might have a protective effect against hypoxia. We synthesized a series of isosorbide mononitrate derivant compounds to test their anti-hypoxia activities. Normobaric hypoxia and hypobaric hypoxia models were used to study the protective role of NO donor in mice. The results showed isosorbide mononitrate derivants had protective effects in hypoxia mice. Among those compounds, acetyl ferulic isosorbide mononitrate (AFIM) was the most effective. It prolonged the survival time during the normobaric hypoxia test. It decreased malondialdehyde (MDA) and H₂O₂ in hypobaric hypoxia mice. The antioxidase activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) remained in normal ranges in the AFIM group. As a sign of mitochondrial dysfunction, the activities of ATPase were down regulated in mice under hypobaric hypoxia conditions. AFIM also protected ATPase activities. The protective effects of AFIM might come from a sustained NO supply and the release of acetyl ferulic acid with anti-oxidant activity.

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This study presents a novel circuit topology for a single-phase inverter using an active power decoupling circuit operated in discontinuous current mode (DCM). In a conventional single-phase grid-tied inverter, bulky capacitors are used in a DC-link to absorb a power ripple with twice the grid frequency. However, electrolytic capacitors limit a converter's lifetime. In contrast, ceramic capacitors are used in the proposed circuit since the required capacitance is reduced. Furthermore, the active power decoupling circuit in DCM has no inductor inside by utilizing the current zero cross featured in DCM for power ripple compensation modes. An experimental verification using a 1-kW prototype shows a 90.2% current ripple reduction caused by the power ripple with twice the grid frequency. The efficiency exceeds 94% in the 20% region of the rated power to 1-kW through 96.0% of the 650W maximum. According to a theoretical evaluation using a Pareto-front optimization assumed as a 3-kW system, the proposed circuit reaches the maximum power density at 20kHz which is 115% higher than that of the passive power decoupling method. The inductor volume in the proposed circuit is reduced by 30.4% compared to a conventional buck-type active power decoupling circuit.

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In recent years, it has been demanding that expanding sustainable industrialization and inno- vation from the background of problems such an aging society with a declining birthrate. For such problems, labor-saving by robots as well as applying human supported robots are essential, and human interaction robot is required that is capable of interaction with the various environment. This paper proposes a new force control technique that realizes stable contact and the robustness of environmental variations.

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Despite the advances in detection of and therapies for various tumors, high rates of treatment failure and mortality still exist throughout the world. These high rates are mainly due to the powerful capability of tumor cells to proliferate and migrate. Recent studies regarding the transient receptor potential (TRP) have indicated that TRP channels are associated with tumors and that TRP channels might represent potential targets for cancer treatment. TRP channels are important calcium-selective ion channels in many different tissues and cell types in mammals and are crucial regulators of calcium and sodium. TRP were first discovered in the photoreceptors of Drosophila with gene defects or mutations. TRP channels can be divided into seven subfamilies: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), TRPA (ankyrin transmembrane protein), and TRPN (NomPC-like). TRPC proteins are conserved across organisms since they are most homologous to Drosophila TRP. TRP superfamilies have been linked to many physiological and pathological functions, including cell differentiation, proliferation, apoptosis, and ion homeostasis. This review focuses on the properties of TRP in oncogenesis, cancer proliferation, and cell migration.

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Multiple sclerosis (MS) is a CD4⁺ T cell-mediated autoimmune disease affecting the central nervous system. It was largely accepted that Th1 cells driven by IL-12 were pathogenic T cells in human MS and experimental autoimmune encephalomyelitis, an animal model of MS. Recent data have established that IL-17-producing CD4⁺ T cells, driven by IL-23 and referred to as Th17 cells, play a pivotal role in the pathogenesis of EAE. A combination of TGF-β and IL-6 induce Th17 cell lineage commitment via expression of transcription factor RORγt. Th17 cells and induced Foxp3⁺ T regulatory cells are in reciprocal position in the T cell lineage commitment governed by TGF-β and IL-6. The vitamin A metabolite retinoic acid is involved in this process via TGF-β dependent induction of Foxp3. We have demonstrated that human Th17 cells could be identified as CCR2⁺ CCR5^- memory CD4⁺ T cells. It is becoming clear that IL-23/Th17 axis also plays an important role in the pathogenesis of various human autoimmune diseases including MS. Additionally, accumulating evidences raise a possibility that CCR2 on Th17 cells may be a therapeutic target in MS.

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The aim of this study was to design a molecular biological tool, using information provided by amplicon pyrosequencing of 16S rRNA genes, that could be suitable for environmental assessment and bioremediation in marine ecosystems. We selected 63 bacterial genera that were previously linked to hydrocarbon biodegradation, representing a minimum sample of the bacterial guild associated with this process. We defined an ecological indicator (ecological index of hydrocarbon exposure, EIHE) using the relative abundance values of these genera obtained by pyrotag analysis. This index reflects the proportion of the bacterial community that is potentially capable of biodegrading hydrocarbons. When the bacterial community structures of intertidal sediments from two sites with different pollution histories were analyzed, 16 of the selected genera (25%) were significantly overrepresented with respect to the pristine site, in at least one of the samples from the polluted site. Although the relative abundances of individual genera associated with hydrocarbon biodegradation were generally low in samples from the polluted site, EIHE values were 4 times higher than those in the pristine sample, with at least 5% of the bacterial community in the sediments being represented by the selected genera. EIHE values were also calculated in other oil-exposed marine sediments as well as in seawater using public datasets from experimental systems and field studies. In all cases, the EIHE was significantly higher in oiled than in unpolluted samples, suggesting that this tool could be used as an estimator of the hydrocarbon-degrading potential of microbial communities.

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Dengue remains a major public health problem in the Philippines. In this study, we determined the circulating dengue serotypes in the Philippines during the 2015–2017 outbreaks using a total of 678 serum samples from 537 individual dengue patients. Following an increase in the number of DENV-4 patients in recent years, we conducted a comprehensive molecular and epidemiology analysis on the DENV-4 strains isolated recently in the Philippines. Two genotypes of DENV-4 have been isolated in the Philippines since 1956: GI and GIIa. The GIIa DENV strains that were isolated in the present study were closely related to a distinct group of GIIa strains that were isolated from the Philippines in 2004. A majority of the isolates of this sub-group have been identified in the Philippines, suggesting that this lineage may have been introduced in the Philippines, and evolved to form the distinct sub-group within GIIa strains. The increase in DENV-4 activity also coincided with the appearance of the GIIa subgroup and the phasing-out of the GI lineage in the Philippines. Overall, our study demonstrates a shift in DENV-4 genotype and epidemic dynamics in a hyperendemic region, suggesting the importance of DENV genetic evolution in establishing and sustaining transmission.

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With the support of emerging technologies such as 5G, machine learning, edge computing and Industry 4.0, the Internet of Things (IoT) continues to evolve and promote the construction of future networks. Existing work on IoT mainly focuses on its practical applications, but there is little research on modeling the interactions among components in IoT systems and verifying the correctness of the network deployment. Therefore, the Calculus of the Internet of Things (CaIT) has previously been proposed to formally model and reason about IoT systems. In this paper, the CaIT calculus is extended by introducing broadcast communications. For modeling convenience, we provide explicit operations to model node mobility as well as the interactions between sensors (or actuators) with the environment. To support the use of UPPAAL to verify the temporal properties of IoT networks described by the CaIT calculus, we establish a relationship between timed automata and the CaIT calculus. Using UPPAAL, we verify six temporal properties of a simple “smart home” example, including Boiler On Manually, Boiler Off Automatically, Boiler On Automatically, Lights On, Lights Mutually, and Windows Simultaneously. The verification results show that the “smart home” can work properly.

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