Regulation of ENaC-mediated alveolar fluid clearance by insulin via PI3K/Akt pathway in LPS-induced acute lung injury

<p>Abstract</p> <p>Background</p> <p>Stimulation of epithelial sodium channel (ENaC) increases Na⁺transport, a driving force of alveolar fluid clearance (AFC) to keep alveolar spaces free of edema fluid that is beneficial for acute lung injury (ALI). It is well recognized that regulation of ENaC by insulin via PI3K pathway, but the mechanism of this signaling pathway to regulate AFC and ENaC in ALI remains unclear. The aim of this study was to investigate the effect of insulin on AFC in ALI and clarify the pathway in which insulin regulates the expression of ENaC in vitro and in vivo.</p> <p>Methods</p> <p>A model of ALI (LPS at a dose of 5.0 mg/kg) with non-hyperglycemia was established in Sprague-Dawley rats receiving continuous exogenous insulin by micro-osmotic pumps and wortmannin. The lungs were isolated for measurement of bronchoalveolar lavage fluid(BALF), total lung water content(TLW), and AFC after ALI for 8 hours. Alveolar epithelial type II cells were pre-incubated with LY294002, Akt inhibitor and SGK1 inhibitor 30 minutes before insulin treatment for 2 hours. The expressions of α-,β-, and γ-ENaC were detected by immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting.</p> <p>Results</p> <p>In vivo, insulin decreased TLW, enchanced AFC, increased the expressions of α-,β-, and γ-ENaC and the level of phosphorylated Akt, attenuated lung injury and improved the survival rate in LPS-induced ALI, the effects of which were blocked by wortmannin. Amiloride, a sodium channel inhibitor, significantly reduced insulin-induced increase in AFC. In vitro, insulin increased the expressions of α-,β-, and γ-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt inhibitor significantly prevented insulin-induced increase in the expression of ENaC and the level of phosphorylated Akt respectively. Immunoprecipitation studies showed that levels of Nedd4-2 binding to ENaC were decreased by insulin via PI3K/Akt pathway.</p> <p>Conclusions</p> <p>Our study demonstrated that insulin alleviated pulmonary edema and enhanced AFC by increasing the expression of ENaC that dependent upon PI3K/Akt pathway by inhibition of Nedd4-2.</p

Downregulation of KLF8 expression by shRNA induces inhibition of cell proliferation in CAL27 human oral cancer cells

Objectives: KLF8 is a member of KLF transcription factors which play an important tolr in oncogenesis. It is barely expressed in normal human epithelial cells but highly overexpressed in several types of human cancer cell lines. In the present study, we investigate the role of KLF8 in oral cancer and the effects of KLF8 knockdown via lentivirus mediated siRNA infection in human adenosquamos carcinoma CAL 27 cells. Study Design: We developed a vector-based siRNA expression system that can induce RNAi in CAL 27 oral cancer cells. Downregulation of KLF8 was confirmed by evaluating GFP expressions, RT-PCR and western blot analysis. Finally, the effects of KLF8 downregulation were analyzed by MTT assay and colony formation assays. Results: The expression levels of KLF8 mRNA and proteins are reduced in CAL 27 cells that transfected with 21- nt siRNA against KLF8. Lentivirus-mediated silencing of KLF8 reduces cell proliferation and colonies number, thereby indicating the role of KLF8 in cell proliferation and tumorigenesis. Conclusions: These results strongly suggest that KLF8 is essential for growth of CAL 27 cancer cells. A better understanding of KLF8 function and processing may provide novel insights into the clinical therapy of oral cancer

Evaluation of a root extract gel from Urtica dioica (Urticaceae) as analgesic and anti-inflammatory therapy in rheumatoid arthritis in mice

Purpose: To develop and characterize an herbal gel prepared from methanol root extract of Urtica dioica (Urticaceae) (Stinging nettle) for the treatment of arthritis in mice.Methods: A methanol root extract from Urtica dioica was prepared, and a gel was then prepared using Carbopol 934. The prepared gel was subjected to various physical tests (color, appearance, pH, texture, viscosity) and in vivo evaluation, including primary skin irritation, analgesic, and anti-inflammatory tests, in arthritic mice and compared with 2 % indomethacin gel, which was used as standard.Results: The prepared herbal gel was of light gray color with a smooth texture. It showed a pH of 7.1 and a viscosity of 21.2 cps. The gel exhibited pseudoplastic rheology, as evidenced by shear thinning with increased shear rate. It was non-irritating to the skin in primary skin irritation test in mice and showed 55.05 % inhibition of paw edema in a carrageenan-induced hind rat paw edema model, comparable to that of the standard gel (53.93 %), after 24 h. The gel showed 58.21 % analgesia, versus 61.19 % analgesia for the indomethacin gel standard in writhing test.Conclusion: The topical gel from methanol root extract of U. dioica may be an efficacious and safe alternative to non-steroidal anti-inflammatory drugs in the treatment of rheumatoid arthritis but this requires further investigations to ascertain its safety and clinical efficacy.Keywords: Rheumatoid arthritis, Urtica dioica, Stinging nettle, Anti-inflammatory activity, Analgesic activity, Herbal therap

catena-Poly[[aqua­dioxidouranium(VI)]-μ3-4,4′-oxydibenzoato]

The title compound, [UO2(C14H8O5)(H2O)]n, is a polymeric UO2 complex bridged by 4,4′-oxydibenzoate ligands. One carboxyl­ate group of the bridging ligand chelates a uranyl cation while the other carboxyl­ate group of the ligand bridges two other two uranyl cations, forming a double-chain polymeric structure. The central UVI atom is seven-coordin­ated in a distorted UO7 penta­gonal-bipyramidal geometry. In the crystal structure, O—H⋯O hydrogen bonding links the polymeric chains into a three-dimensional supra­molecular framework. Within the bridging ligand, the two benzene rings are oriented at a dihedral angle of 59.0 (2)°

Decreased NPC1L1 expression in the liver from Chinese female gallstone patients

<p>Abstract</p> <p>Background</p> <p>Cholesterol gallstone disease is a very common disease in both industrialized and developing countries. Many studies have found that cholesterol gallstones are more common in women than men. The molecular mechanisms underlying the relationship between female gallstone disease and hepatic sterol transporters are still undergoing definition and have not been evaluated in humans.</p> <p>Aims</p> <p>The aim of this study is to probe for underlying hepatic molecular defects associated with development of gallstones in female.</p> <p>Methods/Results</p> <p>Fifty-seven nonobese, normolipidemic Chinese female gallstone patients (GS) were investigated with 12 age- and body mass index-matched female gallstone-free controls (GSF). The bile from the female GS had higher cholesterol saturation than that from the female GSF. The hepatic NPC1L1 mRNA levels were lower in female GS, correlated with SREBP2 mRNA. NPC1L1 downregulation was confirmed at protein levels. Consistently, immunohistochemistry showed decreased NPC1L1 expression in female GS.</p> <p>Conclusions</p> <p>The decreased hepatic NPC1L1 levels in female GS might indicate a downregulated reabsorption of biliary cholesterol in the liver, which, in turn, leads to the cholesterol supersaturation of bile. Our data are consistent with the possibility that hepatic NPC1L1 may be mediated by SREBP2.</p

Few-femtosecond Electron Beam with THz-frequency Wakefield-driven Compression

We propose and demonstrate a novel method to produce few-femtosecond electron beam with relatively low timing jitter. In this method a relativistic electron beam is compressed from about 150 fs (rms) to about 7 fs (rms, upper limit) with the wakefield at THz frequency produced by a leading drive beam in a dielectric tube. By imprinting the energy chirp in a passive way, we demonstrate through laser-driven THz streaking technique that no additional timing jitter with respect to an external laser is introduced in this bunch compression process, a prominent advantage over the conventional method using radio-frequency bunchers. We expect that this passive bunching technique may enable new opportunities in many ultrashort-beam based advanced applications such as ultrafast electron diffraction and plasma wakefield acceleration.Comment: 5 pages, 4 figure

Earthworms Modulate Impacts of Soil Heterogeneity on Plant Growth at Different Spatial Scales

[Abstract] Soil heterogeneity (uneven distribution of soil nutrients and/or other properties) is ubiquitous in nature and can greatly affect plant growth. As earthworm activity can influence nutrient redistribution in the soil, we hypothesize that earthworms may alter the effect of soil heterogeneity on plant growth and this effect may depend on the scale of soil heterogeneity. To test these hypotheses, we grew the clonal grass Leymus chinensis in three soil treatments (heterogeneous large vs. heterogeneous small patch vs. homogeneous soil treatment) with or without earthworms [i.e., Eisenia fetida Savigny (Lumbricidae, epigeic redworm)]. In the heterogeneous treatments, the soil consisted of patches with and without 15N-labeled litter (referred to as high- and low-quality patches, respectively), and in the homogeneous treatment, the soil was an even mixture of the two types of soil patches. Biomass of L. chinensis was significantly higher in the high- than in the low-quality patches, showing the foraging response; this foraging response occurred at both scales and under both earthworm treatments. Compared to the homogeneous treatment, the heterogeneous large patch treatment increased biomass of L. chinensis without earthworms, but decreased it with earthworms. In contrast, biomass of L. chinensis in the heterogeneous small patch treatment did not differ from that in the homogeneous treatment, irrespective of earthworms. Belowground biomass was much greater in the heterogeneous small than in the heterogeneous large patch treatment without earthworms, but it did not differ between these two scale treatments with earthworms. In the heterogeneous treatments, soil 15N was greater in the high- than in the low-quality patches, but this effect became much weaker with than without earthworms, suggesting that earthworm activity homogenized the soil. We conclude that earthworms can change the impact of soil heterogeneity on plant growth via homogenizing the soil, and that this effect of earthworms varies with patch scale. Such scale-dependent interactive effects of soil heterogeneity and earthworms could be a potential mechanism modulating plant community structure and productivity.This study was supported by the National Natural Science Foundation of China (31800341) and the Ten-Thousand-Talent Program of Zhejiang Province (2018R52016)China. National Natural Science Foundation of China; 31800341China. Ten-Thousand-Talent Program of Zhejiang Province; 2018R5201

Spin-resolved imaging of atomic-scale helimagnetism in monolayer NiI2

Identifying intrinsic noncollinear magnetic order in monolayer van der Waals (vdW) crystals is highly desirable for understanding the delicate magnetic interactions at reduced spatial constraints and miniaturized spintronic applications, but remains elusive in experiments. Here, we achieved spin-resolved imaging of helimagnetism at atomic scale in monolayer NiI2 crystals, that were grown on graphene-covered SiC(0001) substrate, using spin-polarized scanning tunneling microscopy. Our experiments identify the existence of a spin spiral state with canted plane in monolayer NiI2. The spin modulation Q vector of the spin spiral is determined as (0.2203, 0, 0), which is different from its bulk value or its in-plane projection, but agrees well with our first principles calculations. The spin spiral surprisingly indicates collective spin switching behavior under magnetic field, whose origin is ascribed to the incommensurability between the spin spiral and the crystal lattice. Our work unambiguously identifies the helimagnetic state in monolayer NiI2, paving the way for illuminating its expected type-II multiferroic order and developing spintronic devices based on vdW magnets.Comment: 22 pages, 4 figure

Redundancy-Free Self-Supervised Relational Learning for Graph Clustering

Graph clustering, which learns the node representations for effective cluster assignments, is a fundamental yet challenging task in data analysis and has received considerable attention accompanied by graph neural networks in recent years. However, most existing methods overlook the inherent relational information among the non-independent and non-identically distributed nodes in a graph. Due to the lack of exploration of relational attributes, the semantic information of the graph-structured data fails to be fully exploited which leads to poor clustering performance. In this paper, we propose a novel self-supervised deep graph clustering method named Relational Redundancy-Free Graph Clustering (R$^2$FGC) to tackle the problem. It extracts the attribute- and structure-level relational information from both global and local views based on an autoencoder and a graph autoencoder. To obtain effective representations of the semantic information, we preserve the consistent relation among augmented nodes, whereas the redundant relation is further reduced for learning discriminative embeddings. In addition, a simple yet valid strategy is utilized to alleviate the over-smoothing issue. Extensive experiments are performed on widely used benchmark datasets to validate the superiority of our R$^2$FGC over state-of-the-art baselines. Our codes are available at https://github.com/yisiyu95/R2FGC.Comment: Accepted by IEEE Transactions on Neural Networks and Learning Systems (TNNLS 2024

Statefinder diagnostic for cosmology with the abnormally weighting energy hypothesis

In this paper, we apply the statefinder diagnostic to the cosmology with the Abnormally Weighting Energy hypothesis (AWE cosmology), in which dark energy in the observational (ordinary matter) frame results from the violation of weak equivalence principle (WEP) by pressureless matter. It is found that there exist closed loops in the statefinder plane, which is an interesting characteristic of the evolution trajectories of statefinder parameters and can be used to distinguish AWE cosmology from the other cosmological models.Comment: 5 pages, 4 figures, accepted by PR