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P2X7 receptor (P2X7R) inhibition is critical for reducing the overactivation of its downstream signaling pathway in autoimmune diseases. Phytochemicals are a source of medicinal compounds for various diseases and contribute to the development of effective and safe P2X7R-targeted drugs. This review is aimed at identifying and screening novel safe, effective, and economically feasible inhibitors of P2X7R from phytochemicals extracted from food and plants. The results of the docking study revealed that the VINA scores of dihydrotanshinone, baicalin, berberine, genistin, dioscin, resveratrol, apigenin, cannabidiol, esculin, and luteolin were lower than or equal to that of A740003 (P2X7R inhibitor). The VINA scores of dihydrotanshinone and baicalin were lower than or equal to JNJ47965567 (P2X7R inhibitor). Dihydrotanshinone and baicalin can be used as lead compounds for P2X7R inhibition. These active ingredients will contribute to the discovery of lead compounds and the development of innovative P2X7R agents for the treatment of autoimmune diseases.

Kaempferol-3-O-rutinoside (KR) is a flavonoid glycoside derived from traditional Chinese medicine, plants, and tea, and has good myocardial protection. This study focuses on the mechanism of myocardial protection with KR and whether myocardial protection can be achieved by activating the adenosine monophosphate-activated protein kinase–silent mating-type information regulation 2 homolog 1 (sirtuin) (AMPK/SIRT1) signal pathway. Molecular docking technique was used to predict the binding affinity of KR to AMPK. The inflammatory injury model of H9c2 cells was established by lipopolysaccharide (LPS) induction. H9c2 cell proliferation was detected by cell counting kit -8 assay. The apoptosis rate was measured by flow cytometry. Levels of interlukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked-immunosorbent serologic assay. AMPK and SIRT1 expression levels were quantified through reverse transcription-polymerase chain reaction and Western blotting assay. Results indicated that KR has a certain binding affinity with AMPK. KR could increase the growth of H9c2 inhibited by LPS, reduce apoptosis rate, and reverse the elevated levels of IL-1β, IL-6, and TNF-α. Furthermore, KR could suppress the expression levels of AMPK and SIRT1, and AMPK-specific inhibitor (Compound C) could significantly counteract the activation of KR, indicating that its anti-inflammatory effect is achieved by regulating the AMPK/SIRT1 signaling pathway.

Supertyphoon rainstorms are apposite examples to evaluate the utility of multisource precipitation products in monitoring and forecasting short-duration heavy rainfall and the resulting intense floods. In this study, the record-breaking floods induced by Typhoon Lekima in Jiao River, China, were retrospectively forecasted. The Xinanjiang (XAJ) model was calibrated based on parameter regionalization derived from SOM+k-means clustering. Via XAJ, the performance of the currently prevailing atmosphere reanalysis (CLDASv2 and CMA-CMORP), quantitative precipitation estimation (QPE) (IMERG-ER and PERSIANN-CCS), and quantitative precipitation forecasts (QPFs) (GRAPES_MESO, ECMWF, and GFS) in monitoring and forecasting Lekima rainfall and flood was comprehensively evaluated. A three-component blended ensemble was proposed, by blending QPE nowcasts with the weighted ensemble of QPFs through a transition of the regional GRAPES_MESO, and compared with two conventional two-component blending methods. The results indicated that the parameter regionalization enabled an explicit consideration of the spatial heterogeneity of basin attributes as well as meteorology, resulting in a minimum NSE of 0.81. CLDASv2 and CMA-CMORPH provided superior spatiotemporal accuracy with a structural similarity index up to 0.75 and NSE > 0.9 for the flood simulation. PERSIANN-CCS rainfall and the driven flood were seriously underestimated by 70% and 80%, respectively. The real-time application of QPFs during the Lekima flood provided encouraging results with a lead time of 40 h. The three-component blended ensemble method resulted in more stable and accurate flood forecasts, especially for the flood peak on 9 August, which was improved by 80%. Our results are expected to present support for real-time flood preparation and mitigation with practical significance.

Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration (IDD). Current limitations of stem cells include with their insufficient cell source, poor proliferation capacity, low nucleus pulposus (NP)-specific differentiation potential, and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation. To address these challenges, embryo-derived long-term expandable nucleus pulposus progenitor cells (NPPCs) and esterase-responsive ibuprofen nano-micelles (PEG-PIB) were prepared for synergistic transplantation. In this study, we propose a biomaterial pre-modification cell strategy; the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis. The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis

The submarine oil pipeline has many advantages, such as large oil transportation capacity, and being fast and economical. However, long-term laid submarine oil pipelines are affected by reciprocating load of water flow, subsidence caused by soil liquefaction, ship anchorage operation, etc. In severe cases, it causes overall distortion of a small section of the submarine pipeline, profoundly affecting the safety of the submarine pipeline, which is a significant safety hazard for the health of the marine environment and potentially impacting social and economic benefits. Taking the Cezi-Zhenhai submarine pipeline in the sea area between Ningbo and Zhoushan as an example, many deformation defects in the pipeline have been found through internal inspection, and there is a trend of further deterioration. However, the existing external detection of submarine pipeline deformation can only collect limited data through mechanical dots for rough inversion. This does not meet the accuracy requirements of repairing existing submarine pipeline clamps. Therefore, we propose a real-time visualization surveying and mapping system for the submarine pipeline based on a 3-D laser and a separately designed electronic control system. Our research team performed actual mapping work for the Cezi-Zhenhai submarine pipeline and achieved an excellent mapping control effect. A steady monitoring image and good control effect of moving parts are obtained, and the data obtained by 3-D laser processing perfectly represent the actual state of the submarine pipeline. Predictably, the large-scale application of this system will provide a solid technical guarantee for the health of submarine pipelines.

Consensus clustering provides an elegant framework to aggregate multiple weak clustering results to learn a consensus one that is more robust and stable than a single result. However, most of the existing methods usually use all data for consensus learning, whereas ignoring the side effects caused by some unreliable or difficult data. To address this issue, in this article, we propose a novel self-paced consensus clustering method with adaptive bipartite graph learning to gradually involve data from more reliable to less reliable ones in consensus learning. At first, we construct an initial bipartite graph from the base results, where the nodes represent the clusters and instances, and the edges indicate that an instance belongs to a cluster. Then, we adaptively learn a structured bipartite graph from this initial one by self-paced learning, i.e., we automatically determine the reliability of each edge with adaptive cluster similarity measuring and involve the edges in bipartite graph learning in order of their reliability. At last, we obtain the final consensus result from the learned structured bipartite graph. We conduct extensive experiments on both toy and benchmark datasets, and the results show the effectiveness and superiority of our method. The codes of this article are released in http://Doctor-Nobody.github.io/codes/code_SCCABG.zip.

To improve the coal recovery rate, paste backfill mining was used for 3# coal seam under the industrial square in Panji No.4 Coal Mine. Theoretical analysis, numerical simulation, and similar simulation were applied to study the underground pressure behavior and the overlying strata movement. Results demonstrate the following. (a) Caving mining exerts IV-level mining-induced damages to ground buildings, while slicing backfill mining only causes I-level mining-induced damages to ground buildings. (b) The maximum surface subsidence coefficient of backfill mining is 0.02, and the maximum surface subsidence value is only 4.12% of that under caving mining. (c) The front abutment pressure peak of the working face in caving mining is 28.31 MPa and only 17.82 MPa in backfill mining, which is only 62.95% of caving mining. The distance from the stress peak to the coal wall decreases from 11.14 to 3.04 m. Therefore, the paste backfilling mining of 3# coal seam below the industrial square of Panji No. 4 Coal Mine can effectively control the overlying strata movement and decrease the surface subsidence significantly. Compared with caving mining, backfill mining significantly relieves the strata pressure behaviors and narrows the distance of mining influence.

In this paper, a kind of superabsorbent resin (SAR) with superior quality for hygiene products was developed using Fructus Aurantii Immaturus pectin (FAIP) from Citrus aurantium L.. FAIP-g-AM/AMPS SAR was established by free radical graft co-polymerization with FAIP as skeleton structure, N, N'-Methylene-bis (acrylamide) (MBA) as the cross-linker. Meanwhile, the functional monomers of acrylamide (AM) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS) were introduced. The structure and morphology of FAIP-g-AM/AMPS were characterized by FTIR

This paper presents an experimental investigation on improving the noise reduction capability of the trailing edge serrations using vortex generators. Experiments were conducted on a 150 mm chord flat plate at four angle of attack between 0° and 9° and flow speeds of 20-50 m/s. The Reynolds number based on the chord length ranges from 2.1×105 to 5×105. Vane type vortex generators with various heights of h/δ = 0.16-0.25 were placed along with the serration roots, where δ is the boundary layer thickness at the trailing edge without the vortex generators. The aeroacoustic measurements were made with a phased microphone array, and the aerodynamic measurement near the trailing edge was measured using a hot-wire. Additionally, the lift and drag forces were measured by load cells. The source integrated noise spectra showed a slight reduction in the trailing edge noise over a broadband frequency range. The generation of streamwise vortices by vortex generators can be identified in the wake measurement. These streamwise vortices were further found to counteract the cross-flow generated at serration roots, hence improving the performance of the serration. Moreover, the presence of low-profile vortex generators was found to have an insignificant effect on the lift and drag coefficients.

Yi-Jin Wu,1– 3,* Sa-Sa Zhang,1,* Qin Yin,1 Ming Lei,2 Qi-Hai Wang,4 Wen-Gang Chen,1 Ting-Ting Luo,1 Peng Zhou,5 Cong-Lan Ji4,6 1Department of Pharmacy, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000, People’s Republic of China; 2Xin’an Medical Research Center, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, People’s Republic of China; 3Vascular Diseases Research Center of Wannan Medical College, Wuhu, 241000, People’s Republic of China; 4School of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, Anhui, 241000, People’s Republic of China; 5School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, 230000, People’s Republic of China; 6Research Center of Integration of Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu, 241000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng Zhou; Cong-Lan Ji, Email zhoupeng@ahtcm.edu.cn; 37709103@qq.comBackground: α-Mangostin (MG) showed the potentials in alleviating experimental arthritis, inhibiting inflammatory polarization of macrophages/monocytes, and regulating peroxisome proliferators-activated receptor γ (PPAR-γ) and silent information regulator 1 (SIRT1) signals. The aim of this study was to analyze the correlations among the above-mentioned properties.Methods: Antigen-induced arthritis (AIA) was established in mouse, which was treated with MG in combination with SIRT1/PPAR-γ inhibitors to clarify the role of the two signals in the anti-arthritic actions. Pathological changes were systematically investigated. Phenotypes of cells were investigated by flow cytometry. Expression and co-localization of SIRT1 and PPAR-γ proteins in joint tissues were observed by the immunofluorescence method. Finally, clinical implications from the synchronous up-regulation of SIRT1 and PPAR-γ were validated by experiments in vitro.Results: SIRT1 and PPAR-γ inhibitors (nicotinamide and T0070097) reduced the therapeutic effects of MG on AIA mice, and abrogated MG-induced up-regulation of SIRT1/PPAR-γ and inhibition of M1 polarization in macrophages/monocytes. MG has a good binding affinity to PPAR-γ, and MG promoted the co-expression of SIRT1 and PPAR-γ in joints. Synchronously activating SIRT1 and PPAR-γ was revealed to be necessary by MG to repress inflammatory responses in THP-1 monocytes.Conclusion: MG binds PPAR-γ and excites this signaling to initiate ligand-dependent anti-inflammatory activity. Due to certain unspecified signal transduction crosstalk mechanism, it then promoted SIRT1 expression and further limited inflammatory polarization of macrophages/monocytes in AIA mice.Graphical Abstract: Keywords: rheumatoid arthritis, mangosteen, metabolism, inflammation, immune

Objective: This study aimed to investigate the significant single nucleotide polymorphisms (SNPs) and genes associated with nine reproduction and morphological traits in three breed populations of Chinese goats.Methods: The genome-wide association of nine reproduction and morphological traits (litter size, nipple number, wattle, skin color, coat color, black dorsal line, beard, beard length, and hind leg hair) were analyzed in three Chinese native goat breeds (n = 336) using an Illumina Goat SNP50 Beadchip.Results: A total of 17 genome-wide or chromosome-wide significant SNPs associated with one reproduction trait (litter size) and six morphological traits (wattle, coat color, black dorsal line, beard, beard length, and hind leg hair) were identified in three Chinese native goat breeds, and the candidate genes were annotated. The significant SNPs and corresponding putative candidate genes for each trait are as follows: two SNPs located on chromosomes 6 (CSN3) and 24 (TCF4) for litter size trait; two SNPs located on chromosome 9 (KATNA1) and 1 (UBASH3A) for wattle trait; three SNPs located on chromosome 26 (SORCS3), 24 (DYM), and 20 (PDE4D) for coat color trait; two SNPs located on chromosome 18 (TCF25) and 15 (CLMP) for black dorsal line trait; four SNPs located on chromosome 8, 2 (PAX3), 5 (PIK3C2G), and 28 (PLA2G12B and OIT3) for beard trait; one SNP located on chromosome 18 (KCNG4) for beard length trait; three SNPs located on chromosome 17 (GLRB and GRIA2), 28 (PGBD5), and 4 for hind leg hair trait. In contrast, there were no SNPs identified for nipple number and skin color.Conclusion: The significant SNPs or genes identified in this study provided novel insights into the genetic mechanism underlying important reproduction and morphological traits of three local goat breeds in Southern China as well as further potential applications for breeding goats.

In the TBM system, the tool system failure is an important factor affecting its driving efficiency. In order to improve the maintenance efficiency of the tool system, this paper designed the failure simulation test platform of the TBM tool system, and according to the force changes of the cutter head when the hob fails in different areas, proposed the tool system failure region location diagnosis algorithm based on SVDD, in order to judge the failure state of the cutter head system and locate the failure region. Experimental results show that the cutter head failure determination and failure region location algorithm proposed in this paper can effectively identify the cutter head region where the failure hob is located.

As the volume of data keeps growing rapidly, more and more servers are continuously added into data centers. The industry experience indicates that, in order to reduce the cost and energy consumption, data enter network (DCN) can be expanded by adding a small number of servers from time to time instead of adding a huge number of servers at a time. The DCN structures with incremental scalability can be expanded gradually while their topological properites are preserved. In order to improve the performance of the DCN, dual-centric DCN structures are proposed. However, the incremental scalabilities of the current dual-centric DCNs are not good. This paper proposes a new type of dual-centric data center network structure called GHDC (Generalized Hypercube Data Center network architecture), which is constructed by using commodity switches and multi-port servers. After analyzing the shortest distance between any two vertices, a routing algorithm is developed. To achieve incremental scalability, two incomplete GHDC structures are proposed. A small number of servers can be added into the incomplete GHDC structures while their topological properties are maintained. The analysis results show that GHDC significantly outperform FCell, FRectangle and FSquare in terms of the incremental scalability and robustness. The average through-put of GHDC is approximately equal to that of FSquare and highter than that of FCell and FRectangle by about 17.45% and 25.5%. Compared with the FCell, FRectangle and FSquare, GHDC reduces the cost andenergy consumption by about 10.84%, 22.85% and 29.55%, respectively.