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Recent research has shown that membrane trafficking plays an important role in canonical Wnt signaling through sequestration of the β-catenin destruction complex inside multivesicular bodies (MVBs) and lysosomes. In this study, we introduce Ouabain, an inhibitor of the Na,K-ATPase pump that establishes electric potentials across membranes, as a potent inhibitor of Wnt signaling. We find that Na,K-ATPase levels are elevated in advanced colon carcinoma, that this enzyme is elevated in cancer cells with constitutively activated Wnt pathway and is activated by GSK3 inhibitors that increase macropinocytosis. Ouabain blocks macropinocytosis, which is an essential step in Wnt signaling, probably explaining the strong effects of Ouabain on this pathway. In Xenopus embryos, brief Ouabain treatment at the 32-cell stage, critical for the earliest Wnt signal in development-inhibited brains, could be reversed by treatment with Lithium chloride, a Wnt mimic. Inhibiting membrane trafficking may provide a way of targeting Wnt-driven cancers.

Background: Rumination has mostly been studied in relation to depression, however, it may also occur in response to positive emotions (i.e., positive rumination) and therefore may be a protective factor related to the maintenance of positive mood. Objective: We hypothesized that daily positive and negative affect would be associated with daily positive and negative rumination even after controlling for trait‐level rumination. Method: We carried out a diary study with university students (n = 178), where participants had to answer short surveys online about their daily affect and daily rumination every evening for 10 days. We analyzed our data with multilevel regression in R. Results: Daily positive and negative affect were significantly associated with daily negative and positive rumination, while trait‐level rumination scores were not. Daily and trait‐level rumination were moderately correlated (r = 0.333–0.440). Conclusions: Our findings highlight that daily rumination plays a more significant role in daily emotional experiences than trait rumination across positive and negative valence domains. Daily negative affect appears to be more closely related to higher daily negative rumination than the lack of daily positive rumination, which could be relevant for intervention strategies. [ABSTRACT FROM AUTHOR]

Despite significant advances in prenatal medicine, spontaneous miscarriage remains one of the most common and serious pregnancy complications, affecting an increasing number of women. Since many aspects of the pathogenesis of spontaneous miscarriage remain unexplained, the aim of this study has been to assess the involvement of the NLRP3 inflammasome as a potential causative factor. The concentrations of NLRP3, IL-1β, IL-18, and cytochrome C in the serum of patients after miscarriage were measured by means of the immunoenzymatic method. In the placental tissue, the expression of NLRP3, IL-1β, IL-18, and Caspase-1 as well as that of the classical apoptosis biomarkers Fas, FasL, Bcl-2, and Ca was evaluated by means of immunohistochemistry techniques. Additionally, in whole blood, the concentrations of elements crucial for pregnancy progression, such as Ca, K, Mg, and Na, were examined by means of the ICP-OES method. Significantly higher concentrations of NLRP3 and IL-18 were demonstrated in the serum of patients with miscarriage as compared to the control group. In the placental tissue samples, a higher expression of IL-1β, IL-18, and Caspase-1 proteins was noted in women who had experienced miscarriage as compared to the control group. At the same time, a significantly lower expression of FasL and Bcl-2 proteins as well as Ca deposits was observed in women after miscarriage as compared to those with a normal pregnancy outcome. Significantly lower concentrations of Ca and K were recorded in the blood of patients with spontaneous miscarriage as compared to pregnant women. The analysis of the results x indicated a greater involvement of the inflammasome in women with spontaneous miscarriage associated with oxidative–antioxidative imbalance than in the case of miscarriage related to NET formation. Our research has provided evidence for the involvement of the inflammasome in the process of spontaneous miscarriage and identifies a new direction for diagnostics that includes NLRP3 as a preventive element in prenatal care, particularly in light of the steadily declining number of pregnancies and the increasing number of reproductive failures. [ABSTRACT FROM AUTHOR]

Hypoxic preconditioning is known to protect against various functional disorders, including skeletal muscle dysfunction. Na,K-ATPase, which plays an important role in adaptation to hypoxia, is critical for maintaining the performance of skeletal muscles, which co-express the α1 and α2 isozymes of the enzyme. Persistent dysfunction of α2 Na,K-ATPase isozyme is characteristic of the motor inactivity of skeletal muscles. In this study, we tested our hypothesis that mild hypoxia is able to improve Na,K-ATPase in disused soleus muscle. Rats were subjected to simulated high-altitude (3000 m above sea level) hypobaric hypoxia (HH) for 3 h using a hypobaric chamber. Then, 18 h after control or HH conditions, rats were subjected to 6 h of hindlimb suspension (HS), a model of skeletal muscle disuse. Isolated soleus muscles were tested. HH itself stably increased the α2 Na,K-ATPase isozyme membrane abundance and its electrogenic activity. These effects were accompanied by a decrease in serum level of circulating endogenous ouabain, a specific ligand for Na,K-ATPase. HS itself caused loss of electrogenic activity of α2 Na,K-ATPase, but pretreatment with HH protected against this impairment. This protective effect was accompanied by an increase in the α2 Na,K-ATPase membrane abundance without a change in total protein content, suggesting an increase in the α2 Na,K-ATPase traffic from the intracellular pool to the sarcolemma; serum ouabain level was significantly increased. We suggest that these findings open a new field for further studies and may have therapeutic implications for disuse-induced skeletal muscle pathology. [ABSTRACT FROM AUTHOR]

Understanding the migration and transformation of nitrogen during high-alkali coal pyrolysis and the influence of sodium on the nitrogen-containing components of coal is of great significance for the clean and efficient utilization of coal. In this study, gas chromatography-mass spectrometry (GC-MS), X-ray photoelectron spectroscopy (XPS) and ultraviolet visible spectroscopy (UV-Vis) were used to analyze the conversion of tar-N, char-N and gas-N during coal pyrolysis and the effect of sodium on the nitrogen-containing pyrolysis products of coal. The experimental results were combined with density functional theory (DFT) calculations to investigate the effect of sodium on the internal conversion process of char-N. The results revealed that a large amount of Na (2.5 wt.%, 3.5 wt.%) can reduce the nitrogen content in coal pyrolysis char, promote the formation of amine and amide in tar-N and inhibit the release of gaseous nitrogen. A small amount of Na (0.5 wt.%, 1.5 wt.%) retains nitrogen in char, reducing the total amount of nitrogen-containing species in the gas phase and tar, which is an effective means to inhibit the transformation of nitrogen to volatile matter. In addition, a large amount of Na promotes the conversion of pyrrole nitrogen (N-5) and pyridine nitrogen (N-6) in char to heterocyclic N in tar. A small amount of sodium promotes the hydrogenation and ring opening of heterocyclic-N in tar to HCN. Na promotes the conversion of N-5 and N-6 in char. DFT calculations further confirmed that the addition of Na significantly reduced the energy barrier of the rate determining step by about 36.6 kJ/mol. [ABSTRACT FROM AUTHOR]

NO heterogeneous reduction by char has a great potential in reducing NOx emission. Notably, Na has a considerable effect on heterogeneous reduction. Herein, the Zhundong demineralization coal and the NaCl addition coal were taken as research objects. The char sample structure is characterized by BET surface area analysis, XRD, and XPS. Experimental and density functional theory were used to explore the macroscopic and microscopic effects of the Na contents on NO heterogeneous reduction by nitrogen-containing char in the reduction zone of staged combustion. The results showed that the properties of char are not the key factors, which affect NO heterogeneous by char at high temperature. Na promoted the adsorption and reduction of NO by improving NO chemisorption energy and reducing the largest reduction energy barrier. The catalytic NO heterogeneous activity depended on the contents of Na. While the 0.6 wt.% NaCl addition had the best catalytic effect, the adsorption capacity and reduction rate of NO were 4.96 times and 1.22 times than DC char, respectively. However, a large amount of Na will cover the active centers on char surface to inhibit NO chemisorption and reduction. The reduction of NO to N2 was accompanied by CO release. According to the simulation results, Na can reduce the largest reaction energy barrier of C(O) complexes desorption to promote the formation of CO. [ABSTRACT FROM AUTHOR]

Background and Aim: The benefits of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in reducing the development of chronic hepatitis B (CHB)‐related hepatocellular carcinoma remain controversial. Whether mortality rates differ between patients with CHB treated with ETV and those treated with TDF is unclear. Methods: A total of 2542 patients with CHB treated with either ETV or TDF were recruited from a multinational cohort. A 1:1 propensity score matching was performed to balance the differences in baseline characteristics between the two patient groups. We aimed to compare the all‐cause, liver‐related, and non‐liver‐related mortality between patients receiving ETV and those receiving TDF. Results: The annual incidence of all‐cause mortality in the entire cohort was 1.0/100 person‐years (follow‐up, 15 757.5 person‐years). Patients who received TDF were younger and had a higher body mass index, platelet count, hepatitis B virus deoxyribonucleic acid levels, and proportion of hepatitis B e‐antigen seropositivity than those who received ETV. The factors associated with all‐cause mortality were fibrosis‐4 index > 6.5 (hazard ratio [HR]/confidence interval [CI]: 3.13/2.15–4.54, P < 0.001), age per year increase (HR/CI: 1.05/1.04–1.07, P < 0.001), alanine aminotransferase level per U/L increase (HR/CI: 0.997/0.996–0.999, P = 0.003), and γ‐glutamyl transferase level per U/L increase (HR/CI: 1.002/1.001–1.003, P < 0.001). No significant difference in all‐cause mortality was observed between the ETV and TDF groups (log–rank test, P = 0.69). After propensity score matching, no significant differences in all‐cause, liver‐related, or non‐liver‐related mortality were observed between the two groups. Conclusions: Long‐term outcomes of all‐cause mortality and liver‐related and non‐liver‐related mortality did not differ between patients treated with ETV and those receiving TDF. [ABSTRACT FROM AUTHOR]

Thyroid hormone deficiency, with a variety of causes and symptoms, is known as hypothyroidism. Morbidity and mortality are increased by untreated hypothyroidism. Midkine is highly expressed during embryogenesis and governs cell proliferation, angiogenesis, anti-apoptotic actions, survival, and migration, though it is commonly low in maturity. Studies demonstrate that MK expression is highly elevated in thyroid cancers and connected to pathological and clinical characteristics, This study evaluates the relationship of MK with thyroid hormone levels in newly diagnosed hypothyroidism and subclinical hypothyroidism compared with healthy. a case-control study was conducted For the period from November 2022 to January 2023. The 120 participants in the current study, who were Baghdad residents between the ages of)20-65(, were divided into three groups: 30 patients were newly diagnosed with hypothyroidism, and 30 patients had subclinical hypothyroidism. In contrast with 60 healthy subjects (control group). Measurements of S.TSH, Total S.T3, and Total S.T4 parameters. were measured on all groups and the results were compared between them by system automatically and (midkine) by ELISA and whole Electrolytes (Na, k, cl) were measured using a Manual spectrophotometer (colorimetric). The Results The midkine levels were measured and compared between the control group with the newly diagnosed hypothyroidism group, and the subclinical hypothyroidism group. There was a difference, but this difference did not reach statistical significance, there was a trend towards higher midkine levels in the NDH group compared to the SCH groups and control (p=0.07). while Statistical analysis indicated a significant difference in the midkine levels were measured and compared between the control group and the newly diagnosed hypothyroidism group (p<0.04). As for Age, weight, height and BMI However, these results were not statistically significant. (The probability value was greater than 0.05). The control group had a mean sodium level of 145.32 ±6.90, the NDH group had a mean sodium level of 144.43 ±6.30, and the SCH group had a mean sodium level of 143.83 ±7.97. Statistical analysis did not show a significant difference in sodium levels among the groups p=0.62. while observing Statistical analysis revealed a significant difference in potassium levels among the groups (p<0.001). A pairwise comparison showed that the control group had higher potassium levels compared to both the NDH and SCH groups (p<0.001). As for chloride, it was noted Statistical analysis indicated a significant difference in chloride levels among the groups (p=0.01). The pairwise comparison revealed that the SCH group had significantly lower chloride levels compared to both the control and NDH groups (p<0.05). [ABSTRACT FROM AUTHOR]