5, 7-Dihalo-8-quinolinol complex inhibits growth of ovarian cancer cells via the downregulation of expression of Wip1

Purpose: To assess the cytotoxic effect of 5, 7-dihalo-8-quinolinol complex (DHQ) on ovarian cancer cells, and the mechanism of action involved.Methods: DHQ-mediated changes in cell viability were determined using MTT assay, while apoptosis was analyzed with flow cytometry. The effect of DHQ on cell migration was determined using inverted microscopy, while its effect on invasiveness was assessed with Giemsa dyeing. FACS Caliburinstrumentation was employed for analyzing the effect of DHQ on the cell cycle. The protein expressions of Wip1 and P53 were assayed by western blotting.Results: DHQ induced cytotoxicity against A2780 and OVCAR 3 cells in the concentration range of 0.25 - 12 μM (p < 0.05). In A2780 and OVCAR 3 cells, treatment with 12 μMDHQ resulted in 69.34 and 65.46 % apoptosis, respectively. The migratory potential and invasiveness of A2780 and OVCAR3 cells were significantly decreased by 12 μMDHQ, relative to untreated cells (p < 0.05). Moreover, treatment with 12 μMDHQ arrested cell cycle at G1/G0 phase in A2780 and OVCAR3 cells, but downregulated the protein expressions of Wip1 expression in A2780 and OVCAR3 cells.Conclusion: DHQ exerts cytotoxic effect on ovarian cancer cell growth via arrest of cell cycle and activation of apoptosis. Moreover, DHQ inhibits the migratory and invasive abilities of the cells. Thus, DHQ is a potential drug candidate for the management of ovarian cancer. Keywords: 5,7-Dihalo-8-quinolinol complex, Ovarian cancer, Cytotoxicity, Apoptosis, Invasiveness, Migration, Cell cycl

Nedd4-2-dependent ubiquitination potentiates the inhibition of human NHE3 by cholera toxin and enteropathogenic Escherichia coli

BACKGROUND & AIMS: Diarrhea is one of the most common illnesses and is often caused by bacterial infection. Recently, we have shown that human Naþ/Hþ exchanger NHE3 (hNHE3), but not non-human NHE3s, interacts with the E3 ubiquitin ligase Nedd4-2. We hypothesize that this property of hNHE3 contributes to the increased severity of diarrhea in humans. METHODS: We used humanized mice expressing hNHE3 in the intestine (hNHE3int) to compare the contribution of hNHE3 and mouse NHE3 to diarrhea induced by cholera toxin (CTX) and enteropathogenic Escherichia coli (EPEC). We measured Naþ/ Hþ exchange activity and fluid absorption. The role of Nedd4-2 on hNHE3 activity and ubiquitination was determined by knockdown in Caco-2bbe cells. The effects of protein kinase A (PKA), the primary mediator of CTX-induced diarrhea, on Nedd4-2 and hNHE3 phosphorylation and their interaction were determined. RESULTS: The effects of CTX and EPEC were greater in hNHE3int mice than in control wild-type (WT) mice, resulting in greater inhibition of NHE3 activity and increased fluid accumulation in the intestine, the hallmark of diarrhea. Activation of PKA increased ubiquitination of hNHE3 and enhanced interaction of Nedd4-2 with hNHE3 via phosphorylation of Nedd4-2 at S342. S342A mutation mitigated the Nedd4-2–hNHE3 interaction and blocked PKA-induced inhibition of hNHE3. Unlike non-human NHE3s, inhibition of hNHE3 by PKA is independent of NHE3 phosphorylation, suggesting a distinct mechanism of hNHE3 regulation. CONCLUSIONS: The effects of CTX and EPEC on hNHE3 are amplified, and the unique properties of hNHE3 may contribute to diarrheal symptoms occurring in humans

Converting brownmillerite to alternate layers of Oxygen-deficient and conductive nano-sheets with enhanced thermoelectric properties

Introducing large oxygen deficiencies while retaining low resistivity is important for enhancing the overall thermoelectric properties in 3d transition-metal oxides. In this study, a new synthesis route to reconstruct the insulating brownmillerite SrCoO2.5 is adapted. Through a step-by-step nano-blocks modification, a series of highly-conductive layered structures is evolved, which are [Sr2O2H2]0.5CoO2, [Sr2O2]0.4CoO2, and [Sr2CoO3]0.57CoO2, while still retaining considerable Seebeck coefficient (˜100 µV K-1). Coexistence of low resistivity and high oxygen deficiency is realized in the latter two polymorphs by forming a majority of sintered oxygen vacancies in the rock-salt layer and a minority of normal oxygen vacancies in the CoO2 layer. A room-temperature in-plane power factor of 3.6 mW K-2 m-1, power output density of 4.5 W m-2 at a temperature difference of 28 K, and an out-of-plane thermal conductivity of 0.33 W K-1 m-1 are obtained in the [Sr2O2]0.4CoO2 thin film that exhibits the highest oxygen deficiency (d = 2.95), which is on par with Bi2Te3, the benchmark. It is pointed out that proper distribution of oxygen vacancy is essential in tailoring the physical and chemical properties of transition-metal oxides. The sintered/normal oxygen vacancy layer model provides guidance to the exploration of materials with both low electric resistivity and thermal conductivity.Peer ReviewedPostprint (author's final draft

Water sorptivity of unsaturated fractured sandstone: fractal modeling and neutron radiography experiment

The spontaneous imbibition of water into the matrix and gas-filled fractures of unsaturated porous media is an important phenomenon in many geotechnical applications. Previous studies have focused on the imbibition behavior of water in the matrix, but few works have considered spontaneous imbibition along fractures. In this work, a new fractal model, considering the water losses from the fracture to the matrix, was established to predict the sorptivity of rough-walled fracture. A fractal model, considering the fractal dimension of tortuosity, was modified to estimate the sorptivity of the matrix. Both of the models have a time exponent α and can be simplified to the classical Lucas–Washburn (L–W) equation with α = 0.50. To verify the proposed models, quantitative data on the imbibition of water in both the matrix and the fracture of unsaturated sandstone were acquired by neutron radiography. The results show that the motion of the wetting front in both the matrix and the fracture does not obey the L–W equation. Both theory and experimental observations indicate that fracture can significantly increase spontaneous imbibition in unsaturated sandstone by capillary action. Compared with the classical L–W equation, the models proposed in this study offers a better description of the dynamic imbibition behaviour of water in unsaturated fractured sandstone and, thus, more reliable predictions of the sorptivity of the matrix and the fracture. Moreover, a new method to estimate the time exponent of rough-walled fracture in sandstone was also provided

High-conductive protonated layered oxides from H2O vapor-annealed brownmillerites

Protonated 3d transition-metal oxides often display low electronic conduction, which hampers their application in electric, magnetic, thermoelectric, and catalytic fields. Electronic conduction can be enhanced by co-inserting oxygen acceptors simultaneously. However, the currently used redox approaches hinder protons and oxygen ions co-insertion due to the selective switching issues. Here, a thermal hydration strategy for systematically exploring the synthesis of conductive protonated oxides from 3d transition-metal oxides is introduced. This strategy is illustrated by synthesizing a novel layered-oxide SrCoO3H from the brownmillerite SrCoO2.5. Compared to the insulating SrCoO2.5, SrCoO3H exhibits an unprecedented high electronic conductivity above room temperature, water uptake at 250 °C, and a thermoelectric power factor of up to 1.2 mW K-2 m-1 at 300 K. These findings open up opportunities for creating high-conductive protonated layered oxides by protons and oxygen ions co-doping.CC acknowledges support from the Spanish Ministry of Science, Innovation, and Universities under the “Ramón y Cajal” fellowship RYC2018-024947-I.Peer ReviewedPostprint (author's final draft

A polymorphism in porcine miR-22 is associated with pork color

MicroRNAs (miRNAs) are posttranscriptional regulators that play key roles in meat color regulation. Changes in miRNA expression affect their target mRNAs, leading to multifunctional effects on biological processes and phenotypes. In this study, a G > A mutation site located upstream of the precursor miR-22 sequence in Suhuai pigs was significantly correlated with the meat color parameter a*(redness) of the porcine longissimus dorsi (LD) muscle. AA genotype individuals had the highest average meat color a* value and the lowest miR-22 level. When G > A mutation was performed in the miR-22 overexpression vector, miR-22 expression significantly decreased. Considering that Ca2+ homeostasis is closely related to pig meat color, our results further demonstrated that ELOVL6 is a direct target of miR-22 in pigs. The effects of miR-22 on skeletal muscle intracellular Ca2+ were partially caused by the suppression of ELOVL6 expression

Optimal Blood Pressure Control Target for Older Patients with Hypertension: A Systematic Review and Meta-Analysis

Objective: This study evaluated the optimal systolic blood pressure (SBP) target for older patients with hypertension.Method: A Bayesian network meta-analysis was conducted. The risk of bias of the included studies was assessed by using a modified version of the Cochrane risk of bias. The trial outcomes comprised the following clinical events: major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, myocardial infarction, heart failure and stroke.Results: A total of six trials were included. We reclassified all treatment therapies into three conditions according to the final achieved SBP after intervention (<130 mmHg, 130–139 mmHg and ≥140 mmHg). Our results demonstrated that anti-hypertensive treatment with an SBP target <130 mmHg, compared with treatment with an SBP target ≥140 mmHg, significantly decreased the incidence of MACE (OR 0.43, 95%CI 0.19–0.76), but no statistical difference was found in other comparisons. Although the results showed a trend toward more intensive anti-hypertension therapy having better effects on preventing cardiovascular mortality, all-cause mortality, myocardial infarction, heart failure, and stroke, no significant differences were found among groups.Conclusions: Our meta-analysis suggested that SBP <130 mmHg might be the optimal BP control target for patients ≥60 years of age; however, further evidence is required to support our findings

Origin and tectonic implications of an Early Paleozoic (460-440 Ma) subduction-accretion shear zone in the northwestern Yunkai Domain, South China

The geological evolution of the Early Paleozoic Wuyi-Yunkai orogen in South China is a scientific question of a long-standing debate. We document the presence of a NE-NEE-striking Early Paleozoic subduction-accretion shear zone, a possible melange belt, in the northwestern Yunkai Domain. The northwestern Yunkai shear zone consists predominantly of tectonically juxtaposed fragments of Early Paleozoic flysch, arc volcanic rocks, and a forearc ophiolite. The Yunkai shear zone displays typical melange structures in several locations; however, these structures are not continuous throughout the shear zone. The shear zone provides evidence for greenschist to amphibolite facies metamorphism and intense deformation resulting from Early Paleozoic to Early Mesozoic tectonic events. The flysch fragments are characterized by northwestward younging, northwestward thrusting, and northwestward migration of deformation and metamorphism. The arc volcanic rocks consist of basaltic-andesite, andesite, and dacite with a mainly sanukitic composition and also include Nb-enriched basalts. They are characterized by enrichment of LREEs, LILEs, Pb and depletion of HFSEs, suggesting a continental forearc or a continental arc tectonic setting. The ophiolitic fragments consist of MORB-like basalt and dolerite/gabbro. They have slightly depleted to flat LREE patterns and are characterized by enrichment of LILEs and Pb and depletion of HFSEs, indicating a continental forearc setting. Zircon U-Pb analyses yield 460-443 Ma and 455-437 Ma ages for the sanukitic volcanic rocks and ophiolitic fragments, respectively, suggesting that they formed in the Late Ordovician to Early Silurian. Both the sanukitic volcanic rocks and ophiolitic fragments possess negative to positive zircon epsilon(Hf)(t) values (-11.0 to +23), indicating that they may have been generated by partial melting of an old subarc mantle wedge source metasomatized by slab-derived fluids and/or melts. Recognition of the Early Paleozoic subduction-related magmatism and subduction-accretion structures in the northwestern Yunkai Domain has important implications for the tectonic history of the Wuyi-Yunkai orogen, South China. Collectively, combined with previous studies, we propose that the Huanan oceanic lithosphere began to subduct southeast- ward beneath the Yunkai terrane (arc) as early as 460 Ma, and the subduction continued between 460 and 440 Ma

Effect of Cr Addition on Microstructure and Properties of AuGa Solder

In order to meet the service requirements of electronic devices working at 300 &deg;C in the fields of energy resource prospecting and space exploration, Cr element was added to modify AuGa solder to improve its high-temperature performance. The results showed that the addition of 0.3 wt.% Cr element reduced the loss of Ga element in the smelting and casting process, and effectively improved the problem of the inhomogeneous microstructure of the solder matrix. On the basis of maintaining the good wettability of the solder, the addition of trace chromium effectively restrains the excessive flux of the solder, and the presence of chromium improves the oxidation resistance of the solder. Furthermore, Cr element optimized the interface morphology and improved the mechanical properties of the solder joint. The shear strength of the AuGa-0.3Cr/Ni joint was 87.2 MPa, which was 13.1% higher than that of the joint without Cr element. After 240 h of aging, the shear strength of the AuGa-0.3Cr joint was still the peak value at 84.1 MPa, which was 16.3% higher than that of the AuGa joint