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91.
    
Primary biliary cholangitis (PBC) has a wide variation in clinical presentation and course. There is no significant correlation between these symptoms and the disease stage, although patients with more advanced stages generally have more symptoms. It is important to develop biomarkers in order to identify patients with an increased risk of complications and end-stage liver disease. This study investigated surrogate markers for risk estimation of PBC-related complications, including a study population of 77 patients with PBC who underwent liver biopsy and were measured for serum levels of macrophage activation markers, soluble CD163 (sCD163), soluble mannose receptor (sMR), and zonulin. Patients with PBC were divided into symptomatic (Group S, n = 20) and asymptomatic (Group A, n = 57) groups. The correlations of histological stages based on both Scheuer and Nakanuma classifications with the three serum markers were investigated. The Nakanuma classification involves grading for liver fibrosis and bile duct loss. The three biomarkers were assessed for their diagnostic ability to identify patients with PBC having high risk of developing complications. The predictive factors of these complications were examined as well. Group S had significantly higher serum sMR (p = 0.011) and sCD163 (p = 0.048) levels versus Group A. A composite index of sMR and sCD163 measurements had significantly better prediction performance than sCD163 alone (p = 0.012), although not when compared to sMR alone (p = 0.129). Serum sMR was an independent factor for developing complications on both univariate (Odds ratio (OR) = 30.20, 95% confidence interval (95% CI): 3.410–267.0, p = 0.00220), and multivariate (OR = 33.70, 95% CI: 3.6600–311.0, p = 0.0019) analyses. Patients with PBC having sMR of ≥56.6 had a higher incidence of clinical complications versus those with a sMR of <56.6. Serum sMR predicts the development of complications in patients with PBC. sMR plus sCD163 showed better predictive power than either marker alone, although the addition of sCD163 did not improve the predictive power of sMR. Future prospective studies are required in order to validate the findings of the present study.  相似文献   
92.
    
Haematopoietic stem cells (HSCs) reside in the bone marrow and are supported by the specialised microenvironment, a niche to maintain HSC quiescence. To deal with haematopoietic equilibrium disrupted during inflammation, HSCs are activated from quiescence directly and indirectly to generate more mature immune cells, especially the myeloid lineage cells. In the process of proliferation and differentiation, HSCs gradually lose their self-renewal potential. The extensive inflammation might cause HSC exhaustion/senescence and malignant transformation. Here, we summarise the current understanding of how HSC functions are maintained, damaged, or exhausted during acute, prolonged, and pathological inflammatory conditions. We also highlight the inflammation-altered HSC niche and its impact on escalating the insults on HSCs.  相似文献   
93.
    
The prorenin/renin receptor ((P)RR) is a multifunctional protein that is widely distributed in various organs. Despite intensive research for more than 20 years, this receptor has not been fully characterized. In this study, we generated mice overexpressing the tubular epithelial (P)RR gene ((P)RR-TG mice) to test the previously reported functional role of (P)RR by Ramkumar et al. in 2015 using tubular specific (P)RR KO mice. (P)RR-TG mice were maintained and analyzed in individual metabolic cages and were administered angiotensin II blocker (ARB), direct renin inhibitor (DRI), and bafilomycin, that is, vacuolar ATPase (V-ATPase) antagonist. (P)RR-TG mice were hypertensive and had alkalized urine with lower osmolality and Na+ excretion. ARB and DRI, but not bafilomycin, concurrently decreased blood pressure. Bafilomycin acidized urine of (P)RR-TG mice, or equivalently this phenomenon restored the effect of overexpressed transgene, suggesting that (P)RR functioned as a V-ATPase in renal tubules. Afterall, (P)RR-TG mice were mated with alternative renin transgenic mice (ARen2-TG), which we identified as intracellular renin previously, to generate double transgenic mice (DT-TG). Lethal renal tubular damage was observed in DT-TG mice, suggesting that intracellular renin may be a ligand for (P)RR in tubules. In summary, (P)RR did not substantially affect the tissue renin-angiotensin system (RAS) in our model of tubular specific (P)RR gene over-expression, but alternative intracellular renin may be involved in (P)RR signaling in addition to conventional V-ATPase function. Further investigations are warranted.  相似文献   
94.
    
Recently, it was demonstrated that the expression of BMAL1 was decreased in the endometrium of women suffering from recurrent spontaneous abortion. To investigate the pathological roles of uterine clock genes during pregnancy, we produced conditional deletion of uterine Bmal1 (cKO) mice and found that cKO mice could receive embryo implantation but not sustain pregnancy. Gene ontology analysis of microarray suggested that uterine NK (uNK) cell function was suppressed in cKO mice. Histological examination revealed the poor formation of maternal vascular spaces in the placenta. In contrast to WT mice, uNK cells in the spongiotrophoblast layer, where maternal uNK cells are directly in contact with fetal trophoblast, hardly expressed an immunosuppressive NK marker, CD161, in cKO mice. By progesterone supplementation, pregnancy could be sustained until the end of pregnancy in some cKO mice. Although this treatment did not improve the structural abnormalities of the placenta, it recruited CD161-positive NK cells into the spongiotrophoblast layer in cKO mice. These findings indicate that the uterine clock system may be critical for pregnancy maintenance after embryo implantation.  相似文献   
95.
    
Interleukin (IL) 23 (p19/p40) plays a critical role in the pathogenesis of psoriasis and is upregulated in psoriasis skin lesions. In clinical practice, anti-IL-23Ap19 antibodies are highly effective against psoriasis. IL-39 (p19/ Epstein-Barr virus-induced (EBI) 3), a newly discovered cytokine in 2015, shares the p19 subunit with IL-23. Anti-IL-23Ap19 antibodies may bind to IL-39; also, the cytokine may contribute to the pathogenesis of psoriasis. To investigate IL23Ap19- and/or EBI3-including cytokines in psoriatic keratinocytes, we analyzed IL-23Ap19 and EBI3 expressions in psoriasis skin lesions, using immunohistochemistry and normal human epidermal keratinocytes (NHEKs) stimulated with inflammatory cytokines, using quantitative real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and liquid chromatography-electrospray tandem mass spectrometry (LC-Ms/Ms). Immunohistochemical analysis showed that IL-23Ap19 and EBI3 expressions were upregulated in the psoriasis skin lesions. In vitro, these expressions were synergistically induced by the triple combination of tumor necrosis factor (TNF)-α, IL-17A, and interferon (IFN)-γ, and suppressed by dexamethasone, vitamin D3, and acitretin. In ELISA and LC-Ms/Ms analyses, keratinocyte-derived IL-23Ap19 and EBI3, but not heterodimeric forms, were detected with humanized anti-IL-23Ap19 monoclonal antibodies, tildrakizumab, and anti-EBI3 antibodies, respectively. Psoriatic keratinocytes may express IL-23Ap19 and EBI3 proteins in a monomer or homopolymer, such as homodimer or homotrimer.  相似文献   
96.
The hyperbranched polymers (HBP-SA-Acs) with both a sulfonic acid group as a functional group and an acryloyl group as a cross-linker at terminals in different ratios of sulfonic acid group/acryloyl group (SO3H/Ac) were successfully synthesized as a new thermally stable proton-conducting electrolyte. The cross-linked hyperbranched polymer electrolyte membranes (CL-HBP-SAs) were prepared by thermal polymerizations of the HBP-SA-Acs using benzoyl peroxide, and their ionic conductivities under dry condition and thermal properties were investigated. The ionic conductivities of the CL-HBP-SAs were found to be in the range of 2.2 × 10−4 to 3.3 × 10−6 S/cm, depending upon the SO3H unit contents, at 150 °C under dry condition, and showed the Vogel-Tamman-Fulcher (VTF) type temperature dependence, indicating that proton transfer is cooperated by local polymer chain motion. All CL-HBP-SAs were thermally stable up to 260 °C, and they had suitable thermal stability as electrolyte membranes for the high-temperature fuel cells under dry condition. Fuel cell measurement using a single membrane electrode assembly cell with a cross-linked electrolyte membrane was successfully performed under non-humidified condition. It was demonstrated that applying the concept of dry polymer system to proton conduction is one possible approach toward high-temperature fuel cells.  相似文献   
97.
It is demonstrated that resonance surface X-ray scattering (RSXS), in which incident X-ray energy close to the Pt LIII absorption edge (11.55 keV) is used, is very useful for the determination of the structure of electrodeposited Pt thin layers on a Au(1 1 1) surface. This technique was applied to characterize the structure of electrodeposited Pt layers on Au(1 1 1) substrates prepared under two extreme conditions, which are known to provide rough and atomically flat layers. Detailed structural information was obtained by RSXS measurements and it was confirmed that the structures of the Pt layers were as reported. Pt atoms of the atomically flat monolayer were found to be situated at the threefold hollow cubic closest packing (ccp) sites of the Au(1 1 1)-(1 × 1) surface.  相似文献   
98.
During pulse discharge sintering (PDS) of Ti/SiC/C powder mixture, combustion synthesis reactions occurred at heating rates above 20 °C/min. With an increase in heating rate, combustion synthesis occurred at higher temperatures. The essential of this combustion reaction is the liquid reaction between Ti and formed Ti5Si3. The exothermic TiC formation during PDS process promotes this liquid reaction. We have found that the combustion reactions alone did not finish the formation reactions for Ti3SiC2, and further heating following the combustion reactions is necessary for the synthesis process of Ti3SiC2.  相似文献   
99.
Because of the improved performance of power devices, the volume of the ac filter inductors used in high‐frequency PWM inverters has been reduced. However, the temperature rise in the filter inductor due to this miniaturization has become more pronounced. Therefore, we have proposed an iron loss calculation method for the ac filter inductor. However, the accuracy of the value calculated via the loss map method cannot be verified, because the iron loss arising during each switching period cannot be measured with conventional power measuring instruments. In order to resolve this problem, we developed an inductor loss analyzer (ILA), which allows precise measurement of the iron loss in the inductor during each switching period. The accuracy of the calculation of iron loss in the filter inductor by the loss map method was verified with the ILA. We found that the value calculated by the loss map method differed slightly from the value measured with the ILA. However, these differences can be reduced if we take into account the accurate flux density calculation and the effect of the duty ratio of PWM pulses on the loss. Finally, we verified that the loss map method can provide accurate iron loss calculations.  相似文献   
100.
Effects of residual pores and optical birefringence on transmission through translucent polycrystalline alumina have been studied with the Mie scattering theory. The in-line and total forward transmissions of the translucent polycrystalline alumina were simulated as a function of porosity, pore radius, and grain size. The model revealed that porosity has a significant effect on both the total forward scattering and the in-line transmission, whereas grain size affects only in-line transmission. The calculated transmittance is in good agreement with the experimental values. The in-line transmission gradually increased with a decrease in grain size, and the effect of birefringence on the total forward transmission is negligible in the visible spectrum. The total forward transmission in the visible spectrum is mainly governed by residual pores.  相似文献   
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