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Rule extraction from black box models is critical in domains that require model validation before implementation, as can be the case in credit scoring and medical diagnosis. Though already a challenging problem in statistical learning in general, the difficulty is even greater when highly nonlinear, recursive models, such as recurrent neural networks (RNNs), are fit to data. Here, we study the extraction of rules from second-order RNNs trained to recognize the Tomita grammars. We show that production rules can be stably extracted from trained RNNs and that in certain cases, the rules outperform the trained RNNs.
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OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Neiguan"(PC6) on cardiac function, cardiac morphology and transient receptor potential channel (TRPC) protein expressions in myocardial tissue of mice with myocardial hypertrophy, so as to explore its mechanisms underlying improvement of myocardial hypertrophy. METHODS: Forty-five male C57BL/6 mice were randomly divided into control, model and EA groups (15 mice/group). The myocardial hypertrophy model was established by subcutaneous injection of isoproterenol hydrochloride (15 mg·kg-1·d-1) for 14 days. The mice of the control group received subcutaneous injection of same amount of normal saline. The mice of the EA group received EA stimulation (frequency of 2 Hz, intensity of 1 mA) of bilateral PC6 for 20 min each time, once a day for 14 consecutive days. After the intervention, the body weight, tibia length and heart weight were measured. The left ventricular ejection fraction (EF), fractional shortening index (FS), left ventricular end-systolic volume (LVEV), left ventricular end-systolic internal diameter (LVID) and left ventricular posterior wall thickness (LVPW) were measured by using echocardiography for evaluating the cardiac function. The mean number and surface area of myocardial cells was detected by wheat germ agglutinin (WGA) staining, and changes of the cardiac morphology were observed under light microscopy after HE staining. The expression levels of TRPC1, TRPC3, TRPC4 and TRPC6 (TRPC1/3/4/6) in the myocardial tissue were detected by real-time quantitative PCR (qPCR) and Western blot, separately. RESULTS: Compared with the control group, the heart-body weight ratio(P<0.05) and heart-weight-to-tibia-length ratio (P<0.01), LVEV and LVID levels, the relative surface area, left ventricular area ratio, and the expression levels of cardiac TRPC1/3/4/6 were significantly increased (P<0.01, P<0.05), while the EF, FS, LVPW, number of cardiomyocytes, and the left ventricular posterior wall ratio were obviously decreased (P<0.01, P<0.05) in the model group. In comparison with the model group, the heart/body weight ratio, heart-weight-to-tibia-length ratio, LVEV and LVID levels, relative surface area, left ventricular area ratio, and the expression levels of cardiac TRPC1/3/4/6 were significantly decreased (P<0.01, P<0.05), while the EF, FS, LVPW, number of cardiomyocytes and left ventricular posterior wall ratio were significantly increased (P<0.01, P<0.05) in the EA group. H.E. staining showed disordered arrangement of cardiomyocytes and obvious myocardial interstitial inflammatory cell infiltration in the model group, and evident reduction of degree of cardiac fibrosis and interstitial edema in the EA group. CONCLUSIONS: EA of PC6 can improve the cardiac function and cardiac morphology in mice with myocardial hypertrophy, which may be related to its functions in down-regulating the expression of transient receptor potential channels.
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Electroacupuntura , Ratones Endogámicos C57BL , Miocardio , Animales , Ratones , Masculino , Humanos , Miocardio/metabolismo , Canales de Potencial de Receptor Transitorio/metabolismo , Canales de Potencial de Receptor Transitorio/genética , Cardiomegalia/metabolismo , Cardiomegalia/terapia , Cardiomegalia/genética , Cardiomegalia/fisiopatología , Puntos de Acupuntura , Canales Catiónicos TRPC/metabolismo , Canales Catiónicos TRPC/genéticaRESUMEN
How to repair dentin-pulp injury effectively has always been a clinical problem, and the comparative study of repair process between different injuries is unknown. Dental pulp stem cells (DPSCs) often are selected as seed cells for the study of dentin-pulp injury repair due to excellent advantages in odontogenesis and pulp differentiation. Although many previous researches have indicated that the Wnt protein and Wnt/ß-catenin signaling pathway were crucial for dental growth, development, and injury repair, the specific mechanism remained unknown. In this study, different dentine-pulp injury models of adult mice were established successfully by abrasion and cutting methods. The gross morphology and micro-CT were used to observe the repair of injured mice incisor in different groups. We found that the repair time of each group was different. The repair time of the cutting group was longer than the abrasion group and the qRT-PCR detection showed that the expression of DSPP in the cutting group was higher than that in the abrasion group, but there was no significant difference in proliferation among the groups. In vivo and cell experiments showed that activation of Wnt/ß-catenin signaling pathway can promote the proliferation and odontoblast differentiation of DPSCs. In addition, by using RNAscope staining, we observed that Wnt10a was mainly expressed in the proliferative region and partially expressed in the odontoblast region. The Western blotting results showed that in the early stage of repair, the expression of Wnt10a increased with the extension of days after injury in both abrasion and cutting group and the increase of Wnt10a was tested obviously on the 5th day after injury. But on the 7th day after injury, the expression of Wnt10a was still obvious in the cutting group, while the expression of Wnt10a was significantly reduced in the abrasion group, which was close to the control group. It is suggested that Wnt10a acts as a repair-related protein and has an important role in tooth injury repair. Wnt10a was activated by R-spondin and LiCl, and Wnt10a-siRNA DPSCs were constructed to inhibit Wnt10a. The results showed that Wnt10a/ß-catenin signaling pathway promoted the proliferation and odontoblast differentiation of DPSCs. It plays a crucial role in the repair process of different injuries. This study enriched the mechanisms of Wnt10a /ß-catenin signaling pathways in different types of dentin-pulp injury repair, which could provide experimental evidences for the target gene screening and also give some new ideas for the subsequent research on the molecular mechanisms of tooth regeneration.
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Vía de Señalización Wnt , beta Catenina , Animales , Ratones , Vía de Señalización Wnt/genética , Western Blotting , Diferenciación Celular/genética , Dentina , Proteínas del Tejido Nervioso , Proteínas Wnt/genéticaRESUMEN
Influences of Glycyrrhetinic acid on expression of inflammatory factors in interleukin (IL)-1ß-induced SW982 cells and its anti-inflammatory effects were discussed in this study. MTT results showed that Glycyrrhetinic acid (≤80 µmol·L-1) almost has no toxicity on SW982 cells. The results of ELISA and real-time PCR showed that Glycyrrhetinic acid (10, 20 and 40 µmol · L-1) can significantly inhibit the expression of inflammatory factors such as IL-6, IL-8 and matrix metalloproteinase-1 (MMP-1). Western blot analysis showed that Glycyrrhetinic acid remarkably blocked the NF-κB signaling pathway in vitro. Molecule docking showed that Glycyrrhetinic acid could bind to the active site (NLS Polypeptide) of NF-κB p65. Furthermore, observation of rat foot swelling proved that Glycyrrhetinic acid had a significant therapeutic effect on adjuvant-induced arthritis (AIA) in rats in vivo. Collectively, all these findings suggested that Glycyrrhetinic acid might be a promising lead compound worthy of further pursuit as anti-inflammation agent.
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This study investigated the seasonal characterization of dissolved organic matter (DOM) in reclaimed wastewater (RW) with a special focus on dissolved organic nitrogen (DON) from two full-scale municipal wastewater reclamation plants (WRPs) where the produced RW was used to augment urban rivers. Results showed that the concentrations of DON in RW ranged from 0.32 mg/L to 1.21 mg/L. A higher seasonal mean value of DON in RW from both of the WRPs was observed in winter (p < 0.05, ANOVA). DON chemical characteristics analysis, including ultrahigh-resolution mass spectrometry and ultrafiltration fractionation, showed that DON in RW exhibits more lability during winter than during the other three seasons. This finding was also supported by the results of an algal bioassay experiment, in which DON bioavailabilities were 63.7 ± 3.0%, 53.0 ± 5.3%, 49.5 ± 0.5%, and 49.8 ± 0.2% for WRP-A and were 60.8 ± 2.4%, 43.7 ± 2.2%, 41.2 ± 1.7%, and 43.1 ± 1.1% for WRP-B in winter, spring, summer, and autumn, respectively. Accordingly, DON in RW during winter is more prone to stimulate natural algae and microorganisms, which gives rise to eutrophication in urban rivers. At the molecular level, the seasonal changes in DON are not coupled with those of DOC, which highlights the necessity of DON measurement to obtain a comprehensive understanding of the seasonal characteristics of DOM in RW and its effect on wastewater reuse in urban rivers.
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Ríos , Aguas Residuales , Cromatografía de Gases y Espectrometría de Masas , Nitrógeno/análisis , Estaciones del AñoRESUMEN
Oxidation of magnesium sulfite (MgSO3) is a crucial step for reclaiming the product in wet magnesia desulfurization processes. Here, for enhancing this reaction, a bimetallic catalyst was developed by loading CoOx and MnOx species on a biomass-derived active carbon (AC) support to minimize the costs and potential environmental risks during catalyst application. The substitution effect of Mn to Co sites was investigated, and a comparison of the catalyst with plain cobalt suggested that the ratio of Co/Mn must be greater than 3. A series of catalyst characterizations was performed to reveal the synergistic effect of Co and Mn in the bimetallic catalyst. The introduction of Mn species not only improved the dispersion of CoOx-MnOx mixed oxide but also generated abundant Co3+ species and surface-adsorbed oxygen, both of which acted as the main active sites for sulfite oxidation. Notably, in the bimetallic catalyst, the presence of Mn4+ species assisted regeneration of Co2+ to Co3+ species, further accelerating sulfite oxidation. Besides, the partial substitution of Co sites by Mn also suppressed the losing of Co species during reaction, favoring to decrease the environmental risk, as well as to save the cost of catalyst.