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Eriodictyol occurs naturally in a variety of fruits and vegetables, and has drawn significant attention for its potential health benefits. This study aims to look into the effects of eriodictyol on acute liver injury (ALI) induced by LPS/D-GalN and elucidate its potential molecular biological mechanisms. A total of 47 targets were predicted for the treatment of ALI with eriodictyol, and the PI3K/AKT signaling pathway played a key role in the anti-ALI processing of this drug. The in vivo experiment showed that eriodictyol can effectively reduce liver function-related biochemical indicators such as ALT, AST, and AKP. Eriodictyol can also up-regulate the levels of SOD and GSH, and inhibit the release of IL-1β, IL-6, and TNF-α. Additionally, TUNEL staining, immunohistochemistry, and RT-PCR experiments showed that eriodictyol activated the PI3K/AKT pathway and decreased the expression of Bax, caspase3, and caspase8 while increasing the expression of Bcl-2 m-RNA. Finally, molecular docking experiments and molecular dynamics simulations confirmed the stable binding between eriodictyol and PI3K, AKT molecules. This study showed that eriodictyol can activate the PI3K/AKT signaling pathway to alleviate ALI-related oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Exploring the complex dynamic relationship between urban–rural integrated development and land-use efficiency can contribute to most efficient urban–rural land-use and the rational promotion of urban–rural integrated development. This study established an evaluation model of urban–rural integrated development, adopted the super-efficiency SBM model to measure land-use efficiency, and studied the evolution of the spatial–temporal patterns of urban–rural integrated development and land-use efficiency coupling in the Yellow River Basin. We also examined the factors affecting them with the help of the coupling coordination degree model, non-parametric kernel density estimation, and geographic probes. The results indicate the following: (1) Within the study period, the coupled coordination of urban–rural integrated development and land-use efficiency was similar to the spatial distribution characteristics of land-use efficiency, both showing a "high at both ends and low in the middle" trend. (2) The coupled coordination increased over time; however, a lagging land-use efficiency was a crucial impediment to improving the coupling coordination degree. (3) Carbon emissions, urbanization rate, and per capita GDP were key drivers. The results of this study can provide a reference for local governments in the Yellow River Basin and other similar areas to propose paths to optimize the allocation of urban and rural land-use. [ABSTRACT FROM AUTHOR]

As urbanization and industrialization have advanced in leaps and bounds, the territorial spatial pattern of Qinghai has experienced profound transformation and reconstruction, which has been directly reflected in land-use changes and affected the eco-environment. In this context, we constructed a functional classification system of "production-living-ecological" (PLE), used remote sensing data for six periods from 1980 to 2020, and employed the land transfer matrix, eco-environmental quality index, ecological contribution rate of land-use transformation and geographical detectors to analyze the changes in the territorial spatial patterns, eco-environmental effects and driving forces of eco-environmental quality. The results revealed that (1) the spatial distribution of the province was characterized by the relative agglomeration of the production and living spaces and the absolute dominance of ecological spaces; (2) The eco-environmental quality of the region portrayed a steady improvement, with a significant reduction in the medium–low and low-quality areas; and (3) the annual average precipitation, proportion of non-agricultural area, and socio-economic factors had a significant impact on the eco-environmental quality of the region, meanwhile, national economy and ecological policies are important indirect driving forces of eco-environmental quality. Our findings will provide guidelines for territorial spatial management and serve as a reference for eco-environmental protection in Qinghai. [ABSTRACT FROM AUTHOR]

A novel swarm intelligence algorithm, discretized grey wolf optimizer (GWO), was introduced as a variable selection tool in edible blend oil analysis for the first time. In the approach, positions of wolves were updated and then discretized by logical function. The performance of a wolf pack, the iteration number and the number of wolves were investigated. The partial least squares (PLS) method was used to establish and predict single oil contents in samples. To validate the method, 102 edible blend oil samples containing soybean oil, sunflower oil, peanut oil and sesame oil were measured by an ultraviolet-visible (UV-Vis) spectrophotometer. The results demonstrated that GWO-PLS models can provide best prediction accuracy with least variables compared with full-spectrum PLS, Monte Carlo uninformative variable elimination-PLS (MCUVE-PLS) and randomization test-PLS (RT-PLS). The determination coefficients (R2) of GWO-PLS were all above 0.95. Therefore, the research indicates the feasibility of using discretized GWO for variable selection in rapid determination of quaternary edible blend oil. [ABSTRACT FROM AUTHOR]

It has been reported that neutrophil extracellular traps (NETs) involve inflammation, coagulation and cell death. Acute lung injury is also considered to be connected with NETs. Deoxyribonuclease I (DNase-1), a clinical medication for the respiratory system, has been reported to degrade cell-free DNA (cfDNA), which is the main component of NETs. Herein, we did research to clarify the therapeutic value of DNase-1 in NPE after SAH. In this model, we found that the treatment of DNase-1 remarkably decreased lung water, neutrophilic infiltration and inflammation. In addition, DNase-1 inhibited the NETs and proinflammatory subtype transition of the macrophages. Moreover, the depletion of neutrophil also verified the role of NETs in NPE. Our results suggest that DNase-1 has the potential to effectively relieve the NPE after SAH and to be a clinical drug for use after SAH. [ABSTRACT FROM AUTHOR]

Tea residue, as a byproduct in tea processing, is highly nutritious and can be used as a good raw material for ruminant feed. This study aimed to investigate the effects of Lactiplantibacillus plantarum (L. plantarum) and Bacillus licheniformis (B. licheniformis) mixed fermentation of tea residue mixture (tea residue:wheat bran, 7:3) on chemical composition, bacterial community, and rumen degradation rate. Changes in chemical composition and bacterial community were evaluated after 0 (F0), 1 (F1), 3 (F3), and 5 (F5) days of fermentation. The rumen degradation rate was studied by the in situ nylon bag method. Compared with group F0, acid soluble protein in other groups increased while pH and neutral detergent fiber decreased (p < 0.05). The group F5 was the best. The diversity of bacterial communities in group F0 was significantly lower than those in the other groups (p < 0.05). The relative abundance of phylum Firmicutes and the genus Lactobacillus increased with increasing fermentation time. The rumen degradation rates of dry matter, crude protein, neutral detergent fiber, and acid detergent fiber were increased after fermentation. In conclusion, mixed fermentation of tea residue by L. plantarum and B. licheniformis can ameliorate chemical composition, reduce bacterial community diversity, and improve the rumen degradation rate. [ABSTRACT FROM AUTHOR]

Innovations differ substantially in their qualities, from major breakthroughs to small incremental refinements. What is the relationship between product market competition and the quality of innovations? We develop a model where competition encourages high-quality firms to innovate but discourages low-quality firms from innovating and examine the impact of competition on the quality of innovations, taking the implementation of the negative list system for market access in China as a natural experiment. It is found that competition has twofold impacts on the incentives of innovation and that competition improves the overall innovation quality through the improvement of innovation resource allocation. More competition implies a higher elasticity of substitution, leading to stronger incentives for innovation. Meanwhile, competition also decreases industry profits and increases the cost of innovation, which reduces the expected return on innovation, resulting in fewer incentives for innovation. The findings suggest that while R&D subsidies increase aggregate R&D investment, they encourage the survival and expansion of low-quality firms at the expense of high-quality firms and lead to misallocation of R&D resources, resulting in the decline of overall innovation qualities. [ABSTRACT FROM AUTHOR]

DJ-1 has been shown to play essential roles in neuronal protection and anti-inflammation in nervous system diseases. This study aimed to explore how DJ-1 regulates neuroinflammation after traumatic spinal cord injury (t-SCI). The rat model of spinal cord injury was established by the clamping method. The Basso, Beattie, Bresnahan (BBB) score and the inclined plane test (IPT) were used to evaluate neurological function. Western blot was then applied to test the levels of DJ-1, NLRP3, SOCS1, and related proinflammatory factors (cleaved caspase 1, IL-1β and IL-18); ROS level was also examined. The distribution of DJ-1 was assessed by immunofluorescence staining (IF). BSCB integrity was assessed by the level of MMP-9 and tight junction proteins (Claudin-5, Occludin and ZO-1). We found that DJ-1 became significantly elevated after t-SCI and was mainly located in neurons. Knockdown of DJ-1 with specific siRNA aggravated NLRP3 inflammasome-related neuroinflammation and strengthened the disruption of BSCB integrity. However, the upregulation of DJ-1 by Sodium benzoate (SB) reversed these effects and improved neurological function. Furthermore, SOCS1-siRNA attenuated the neuroprotective effects of DJ-1 and increased the ROS, Rac1 and NLRP3. In conclusion, DJ-1 may alleviate neuroinflammation and the related BSCB destruction after t-SCI by suppressing NLRP3 inflammasome activation by SOCS1/Rac1/ROS pathways. DJ-1 shows potential as a feasible target for mediating neuroinflammation after t-SCI. [ABSTRACT FROM AUTHOR]

Simple Summary: AXL is a receptor tyrosine kinase belonging to the TAM (Tyro3, Axl and Mer) family. The AXL protein plays an important role in promoting cancer development, such as proliferation, migration, invasion and survival of cancer cells. In this study, we used mass spectrometry-based proteomics to quantify the cancer signaling regulated by AXL activation. Our study identified more than 1000 phosphotyrosine sites and discovered that activation of AXL can upregulate multiple cancer-promoting and cell migration/invasion-related signaling pathways. We also observed significant crosstalk as evidenced by rapid phosphorylation of multiple receptor tyrosine kinases and protein tyrosine phosphatases, including PTPN11 and PTPRA, upon GAS6 stimulation. These discoveries should serve as a potentially useful resource for studying AXL functions as well as for the development of effective therapeutic options to target AXL. Overexpression and amplification of AXL receptor tyrosine kinase (RTK) has been found in several hematologic and solid malignancies. Activation of AXL can enhance tumor-promoting processes such as cancer cell proliferation, migration, invasion and survival. Despite the important role of AXL in cancer development, a deep and quantitative mapping of its temporal dynamic signaling transduction has not yet been reported. Here, we used a TMT labeling-based quantitative proteomics approach to characterize the temporal dynamics of the phosphotyrosine proteome induced by AXL activation. We identified >1100 phosphotyrosine sites and observed a widespread upregulation of tyrosine phosphorylation induced by GAS6 stimulation. We also detected several tyrosine sites whose phosphorylation levels were reduced upon AXL activation. Gene set enrichment-based pathway analysis indicated the activation of several cancer-promoting and cell migration/invasion-related signaling pathways, including RAS, EGFR, focal adhesion, VEGFR and cytoskeletal rearrangement pathways. We also observed a rapid induction of phosphorylation of protein tyrosine phosphatases, including PTPN11 and PTPRA, upon GAS6 stimulation. The novel molecules downstream of AXL identified in this study along with the detailed global quantitative map elucidating the temporal dynamics of AXL activation should not only help understand the oncogenic role of AXL, but also aid in developing therapeutic options to effectively target AXL. [ABSTRACT FROM AUTHOR]

In this paper, we propose a novel clustering approach based on P systems and grid- density strategy. We present grid-density based approach for clustering high dimensional data, which first projects the data patterns on a two-dimensional space to overcome the curse of dimensionality problem. Then, through meshing the plane with grid lines and deleting sparse grids, clusters are found out. In particular, we present weighted spiking neural P systems with anti-spikes and astrocyte (WSNPA2 in short) to implement grid-density based approach in parallel. Each neuron in weighted SN P system contains a spike, which can be expressed by a computable real number. Spikes and anti-spikes are inspired by neurons communicating through excitatory and inhibitory impulses. Astrocytes have excitatory and inhibitory influence on synapses. Experimental results on multiple real-world datasets demonstrate the effectiveness and efficiency of our approach. [ABSTRACT FROM AUTHOR]