Atox1 regulates macrophage polarization in intestinal inflammation via ROS-NLRP3 inflammasome pathway.

BACKGROUND: Inflammation and oxidative stress play an important role in the pathophysiology of inflammatory bowel disease (IBD). This study aimed to explore the effects of copper chaperone Antioxidant-1 (Atox1) on macrophages in a mouse model of intestinal inflammation. METHODS: A mouse model of TNBS-induced colitis was established and verified using the disease activity index. Atox1 conditional knockout mice were applied. The proportion of macrophages in colonic lamina propria mononuclear cells and ROS production were analyzed using flow cytometry. Inflammatory cytokines were measured using ELISA. Expression of macrophage M1/M2 polarization markers, p47phox, NLRP3, and Caspase-1 p20 was measured using quantitative RT-PCR and Western blotting. RESULTS: Atox1 expression was up-regulated in colon tissues of TNBS-induced colitis mice. Macrophages isolated from TNBS-induced colitis mice showed M1 polarization and nuclear translocation of Atox1. Inhibiting copper chaperone activity decreased p47phox, ROS production, and M1 polarization induced by CuCl2 in macrophages. TNBS induced up-regulation of inflammatory cytokines, M1 polarization markers, and p47phox expression in mice, an effect which was preempted by Atox1 knockout. Inflammatory cytokines and expression of M1 polarization markers, p47phox, NLRP3, Caspase-1 p20 were also increased in macrophages isolated from TNBS-induced colitis mice. These changes were alleviated in mice with Atox1 knockout. The effects of Atox1 on macrophage polarization were mediated via the ROS-NLRP3 inflammasome pathway. CONCLUSION: Atox1 plays a pro-inflammatory role, promotes M1 polarization of macrophages, and increases the concentrations of pro-inflammatory cytokines in intestinal tissue by regulating the ROS-NLRP3 inflammasome pathway. Atox1 is a potential therapeutic target in IBD.

Enabling Electrochemical-Mechanical Robustness of Ultra-High Ni Cathode via Self-Supported Primary-Grain-Alignment Strategy.

The electrochemical-mechanical degradation of ultrahigh Ni cathode for lithium-ion batteries is a crucial aspect that limits the cycle life and safety of devices. Herein, the study reports a facile strategy involving rational design of primary grain crystallographic orientation within polycrystalline cathode, which well enhanced its electro-mechanical strength and Li+ transfer kinetics. Ex situ and in situ experiments/simulations including cross-sectional particle electron backscatter diffraction (EBSD), single-particle micro-compression, thermogravimetric analysis combined with mass spectrometry (TGA-MS), and finite element modeling reveal that, the primary-grain-alignment strategy effectively mitigates the particle pulverization, lattice oxygen release thereby enhances battery cycle life and safety. Besides the preexisting doping and coating methodologies to improve the stability of Ni-rich cathode, the primary-grain-alignment strategy, with no foreign elements or heterophase layers, is unprecedently proposed here. The results shed new light on the study of electrochemical-mechanical strain alleviation for electrode materials.

Apigenin reduces the suppressive effect of exosomes derived from irritable bowel syndrome patients on the autophagy of human colon epithelial cells by promoting ATG14.

BACKGROUND: Inflammatory bowel disease (IBS) is a chronic disorder of the gastrointestinal tract. Exosomes have been involved in various pathological processes including IBS. Apigenin has been reported to suppress inflammatory bowel disease (IBS). However, the regulatory roles of exosomes derived from IBS patients (IBS-exos) on human colon epithelial cells are still unclear. METHODS: Exosomes were collected from IBS patients (IBS-exos) and co-cultured with CACO-2 cells. Apigenin was used to treat IBS-exos-treated CACO-2 cells. By exploring the public data bank, we figured out the regulators control the autophagy of CACO-2 cells. RESULTS: Administration of apigenin dose-dependently abolished the inhibitory effect of IBS-exo on the autophagy of CACO-2 cells. A mechanistic study showed that miR-148b-3p bound to 3'UTR to suppress ATG14 and decrease autophagy. Moreover, results suggested that ATG14 overexpression promoted the autophagy of CACO-2 cells in the presence of miR-148b-3p mimic. CONCLUSION: The current study showed that apigenin dose-dependently abolished the inhibitory effect of IBS-exo on CACO-2 cell autophagy by regulating miR-148b-3p/ATG14 signaling.

Spark Plasma Sintering of AlN/Al Functionally Graded Materials.

In this paper, six-layer AlN/Al gradient composites were prepared by a spark plasma sintering process to study the influences of sintering temperature and holding time on the microstructure and mechanical properties. The well-bonded interface enables the composite to exhibit excellent thermal and mechanical properties. The hardness and thermal expansion properties of the composite exhibit a gradient property. The hardness increased with the volume fraction of AlN while the CTE decreased as the volume fraction of AlN. The thermal expansion reaches the lowest value of 13-14 ppm/K, and the hardness reaches the maximum value of 1.25 GPa, when the target volume fraction of AlN is 45%. The simulation results show that this gradient material can effectively reduce the thermal stress caused by the mismatch of the thermal expansion coefficient as a transmitter and receiver (T/R) module. This paper attempts to provide experimental support for the preparation of gradient Al matrix composites.

Rab5a Promotes Cytolethal Distending Toxin B-Induced Cytotoxicity and Inflammation.

The cytolethal distending toxin B subunit (CdtB) induces significant cytotoxicity and inflammation in many cell types that are involved in the pathogenesis of postinfectious irritable bowel syndrome (PI-IBS). However, the underlying mechanisms remain unclear. This study tested the potential role of Rab small GTPase 5a (Rab5a) in the process. We tested mRNA and protein expression of proinflammatory cytokines (interleukin-1ß [IL-1ß] and IL-6) in THP-1 macrophages by quantitative PCR (qPCR) and enzyme-linked immunosorbent assays (ELISAs), respectively. In the primary colonic epithelial cells, Cdt treatment induced a CdtB-Rab5a-cellugyrin association. Rab5a silencing, by target small hairpin RNAs (shRNAs), largely inhibited CdtB-induced cytotoxicity and apoptosis in colon epithelial cells. CRISPR/Cas9-mediated Rab5a knockout also attenuated CdtB-induced colon epithelial cell death. Conversely, forced overexpression of Rab5a intensified CdtB-induced cytotoxicity. In THP-1 human macrophages, Rab5a shRNA or knockout significantly inhibited CdtB-induced mRNA expression and production of proinflammatory cytokines (IL-1ß and IL-6). Rab5a depletion inhibited activation of nuclear factor-κB (NF-κB) and Jun N-terminal protein kinase (JNK) signaling in CdtB-treated THP-1 macrophages. Rab5a appears essential for CdtB-induced cytotoxicity in colonic epithelial cells and proinflammatory responses in THP-1 macrophages.

Ce-Substituted Nanograin Na3Zr2Si2PO12 Prepared by LF-FSP as Sodium-Ion Conductors.

The urgent need for high-performance solid electrolytes has aroused considerable focus on NASICON ceramics. Optimization of processing routes to dense, defect-free materials has yet to receive sufficient attention to date. Although traditional solid-state reaction methods followed by repetitive ball milling and sintering up to 10 h above 1200 °C are common place, the resulting average particle sizes are usually too large to produce dense, robust structures because of excessive grain growth. In this study, nanopowders (NPs) are produced, which offer a superior opportunity to make dense, high-phase-purity sintered bodies. Here, we report on the effect of sintering conditions on the microstructures and phase of Ce4+-substituted NASICON samples, Na3CexZr2-xSi2PO12 (x = 0, 0.1, 0.2, 0.3). NPs permit processing fine-grained solid-state electrolytes with 98% relative density at 1100 °C/5 h. In addition, Rietveld refinement was applied to evaluate 3-D Na-ion diffusion channels among different NASICON samples. Also, it is found that adding 5 at % Ce4+ does not change the phase structure but dramatically enlarges the Na+ diffusion "bottleneck" from 5.4 to 5.6 Å2. This may be one reason for these samples to exhibit conductivities of 2.4 × 10-2 S cm-1 at 140 °C.

Expression and clinical significance of 5-HT and 5-HT3R in the intestinal mucosa of patient with diarrhea-type irritable bowel syndrome.

Expression levels and clinical significance of 5-HT and 5-HT3R in the intestinal mucosa tissue of patients with diarrhea-type irritable bowel syndrome (D-IBS) were investigated. A retrospective analysis was performed on 46 tissue specimens (observation group) of the intestinal mucosa of patients with D-IBS, who were diagnosed in the Tongde Hospital of Zhejiang Province and received colonoscopy from March 2016 to December 2017, and 18 tissue specimens (control group) of the intestinal mucosa of healthy subjects who received physical examinations. The expression levels of 5-HT and 5-HT3R in the intestinal mucosa tissue of patients in the observation and control group were detected by ELISA, and the relationship between 5-HT, 5-HT3R and the clinicopathological parameters of patients with D-IBS was analyzed. Pearson's correlation analysis was used to analyze the correlation of 5-HT and 5-HT3R in the intestinal mucosa tissue of patients with D-IBS. The expression levels of 5-HT and 5-HT3R in the intestinal mucosa tissue of patients in the observation group were significantly higher than those of the patients in the control group (344.86±67.52 ng/ml and 13.04±8.34 pg/ml) (P<0.001). There was a positive correlation between the expression level of 5-HT and the expression level of 5-HT3R in the intestinal mucosa tissue of patients with D-IBS (r=0.725, P<0.001). The expression levels of 5-HT and 5-HT3R in the intestinal mucosa tissue of patients with D-IBS were both significantly higher than those of the healthy subjects. The expression levels of 5-HT and 5-HT3R in patients with D-IBS were correlated with age, sex and the history of gastrointestinal infection. 5-HT and 5-HT3R may be involved in the pathogenesis of D-IBS, and potentially used for clinical treatment.

Thermal mismatch strain induced disorder of Y2Mo3O12 and its effect on thermal expansion of Y2Mo3O12/Al composites.

Fully dense Y2Mo3O12/Al composites were prepared by squeeze-casting. Relatively mild conditions of 750 °C/20 min/50 MPa were used in order to avoid reaction of the components. SEM, Raman spectroscopy, XRD and dilatometry were used to characterize the microstructures and morphologies of the composites. Zero thermal expansion was achieved in the temperature range where the thermal mismatch strain was zero. We show that the CTE mismatch of Al and Y2Mo3O12 results in compressive and tensile strains that distort the Y2Mo3O12 lattice. We establish a novel method to measure the negative thermal expansion (NTE) materials' CTE under strain by measuring the composites' CTE and calculating the thermal mismatch strain between the NTE ceramic and the metal matrix. The relationship between thermal strain and Raman shift is established and measured and the simulated results are in good agreement. We also find Y2Mo3O12 to have a positive CTE when the surface strain is ≥0.80 × 10-2%.

Activation of 5-HT and NR2B contributes to visceral hypersensitivity in irritable bowel syndrome in rats.

The roles of 5-hydroxytryptamine (5-HT) and spinal N-methyl-D-aspartic acid receptor 2B (NR2B) in visceral hypersensitivity were investigated. A rat model with irritable bowel syndrome (IBS) was established by intracolonic injections of acetic acid onpost-natal days 8-21. Rats were randomly divided into five groups: normal intact (control) group, IBS model group, Ro25-6981-treated IBS rats (Ro25-6981, a NR2B antagonist) group, amitriptyline-treated IBS rats (amitriptyline, a 5-HT antagonist) and Ro25-6981 plus amitriptyline-treated IBS rats (Ro25-6981+amitriptyline) group. The expressions of 5-HT, NR2B, 5-HT2AR, 5-HT7R, SERT, TNF-α and IL-1ß in colon, dorsal root ganglion (DRG) and hypothalamus, respectively, were measured by Immunohistochemical staining, Real-Time Reverse Transcription-PCR and Western blotting. Our results showed increased DRG and hypothalamus expression of 5-HT, NR2B, 5-HT2AR, 5-HT7R in IBS model group and decreased expression of those in Ro25-6981 and amitriptyline alone or both treatment groups. Moreover, SERT expression was decreased in colorectal, DRG and hypothalamus of ISB model rats, but increased by Ro25-6981 and amitriptyline alone or both treatments. Ro25-6981 and amitriptyline treatment also decreased colorectal expression of TNF-α and IL-1ß induced by IBS model. In conclusion, activation of 5-HT and NR2B may play a crucial role in visceral hypersensitivity in irritable bowel syndrome in rats.

Anti-hypertensive effects of laiju extract in two different rat models.

The aim of the study was to evaluate whether laiju extract (LJE) from Semen Raphani and Flos Chrysanthemi has an anti-hypertensive effect in renal hypertensive rat (RHR) and spontaneous hypertensive rat (SHR). LJE was prepared by extracting dried Semen Raphani and Flos Chrysanthemi with 70% ethanol. RHR and SHR models were prepared by standard methods. Forty RHRs and 40 SHRs were randomly divided into high LJE (300 mg/kg), moderate LJE (200 mg/kg), low LJE (100 mg/kg) and saline control four groups (n=10), respectively. Compared with saline control, blood pressure was significantly lowered at 6 and 5 hours in high and moderate LJE respectively in both RHR and SHR groups. However, blood pressure was significantly lowered at 2 and 3 hours in low LJE in both RHR and SHR groups, respectively. Compared with saline control, blood pressure remained significantly lower in SHR in all dosage groups with a single daily dose for 28 days of study. LJE has potential in the prevention management of hypertension. Further studies are needed to identify the active chemical constituents and mechanisms of action of LJE.