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This study investigates the advantages of combining Spark Plasma Sintering (SPS) with Laser Cladding (LC) technology in the production of AlCoCrFeNi high-entropy alloy (HEA). By comprehensively applying SPS and LC composite processing techniques, we achieve rapid preparation of high-performance AlCoCrFeNi HEA. SPS technology enables rapid sintering under high-temperature conditions, while LC technology allows precise control of microstructure generation on the workpiece surface. Experimental results show that AlCoCrFeNi HEA prepared by single SPS technology exhibits a body-centered cubic (BCC) solid solution structure, while AlCoCrFeNi HEA processed with a combination of SPS and LC techniques demonstrates a complex microstructure consisting of equiaxed BCC phase, uniformly distributed granular face-centered cubic (FCC) solid solution, and α-Al2O3 ceramic phase. Composite processing also eliminates voids and pores caused by single SPS processing, resulting in AlCoCrFeNi HEA with low porosity. Furthermore, the maximum hardness of AlCoCrFeNi HEA produced by composite processing technology is approximately 644.1HV, significantly higher than that of AlCoCrFeNi HEA processed solely by SPS (approximately 328.7HV). Wear test results show that AlCoCrFeNi HEA processed by composite machining exhibits significant advantages in wear resistance, with the width and depth of wear tracks significantly reduced compared to AlCoCrFeNi HEA processed solely by SPS technology, with a 33.17% higher wear rate. In conclusion, composite processing using SPS combined with LC technology enables rapid preparation of AlCoCrFeNi HEA with low porosity, high hardness, and high wear resistance.

Herein, laser remelting (LR) and hot press sintering (HPS) were combined to process high-entropy alloy (HEA) and strengthen desirable microstructure. The microstructural changes of HEA before and after LR processing were experimentally investigated. In Scanning Electron Microscope (SEM) and electron backscatter diffraction (EBSD) observations, it was found that the microstructure of the remelting zone was mainly composed of dendritic isometric crystals, and the laser remelting technique can refine the grain structure of HEA. The combined strengthening features of dislocations and twinning were observed by Transmission electron microscopy (TEM), and the phase structure of the grains was analyzed in conjunction with the X-ray diffraction(XRD) analysis, confirming the presence of B2 with BCC solid-solution and FCC phase. Finally, micron-sized scratches, tensile experiments and microhardness experiments were performed, and it was found that the Mechanical properties of the remelting zone were significantly enhanced. It was demonstrated that the strengthening of HEA, sintered by LR and HPS techniques, is due to the synergistic influence of various strengthening mechanisms, such as fine grain strengthening, dislocation strengthening, solid-solution strengthening and twinning strengthening.

Summary: Background: An intergenic region at chromosome 4q31 is one of the most significant regions associated with COPD susceptibility and lung function in GWAS. In this region, the implicated causal gene HHIP has a unique epithelial expression pattern in adult human lungs, in contrast to dominant expression in fibroblasts in murine lungs. However, the mechanism underlying the species-dependent cell type-specific regulation of HHIP remains largely unknown. Methods: We employed snATAC-seq analysis to identify open chromatin regions within the COPD GWAS region in various human lung cell types. ChIP-quantitative PCR, reporter assays, chromatin conformation capture assays and Hi-C assays were conducted to characterize the regulatory element in this region. CRISPR/Cas9-editing was performed in BEAS-2B cells to generate single colonies with stable knockout of the regulatory element. RT-PCR and Western blot assays were used to evaluate expression of HHIP and epithelial–mesenchymal transition (EMT)-related marker genes. Findings: We identified a distal enhancer within the COPD 4q31 GWAS locus that regulates HHIP transcription at baseline and after TGFβ treatment in a SMAD3-dependent, but Hedgehog-independent manner in human bronchial epithelial cells. The distal enhancer also maintains chromatin topological domains near 4q31 locus and HHIP gene. Reduced HHIP expression led to increased EMT induced by TGFβ in human bronchial epithelial cells. Interpretation: A distal enhancer regulates HHIP expression both under homeostatic condition and upon TGFβ treatment in human bronchial epithelial cells. The interaction between HHIP and TGFβ signalling possibly contributes to COPD pathogenesis. Funding: Supported by NIH grants R01HL127200, R01HL148667 and R01HL162783 (to X. Z).

The sedimentary structure is important for the engineering design, operation, and safety evaluation of tailing dams. For upstream-method tailing dams, tailing slurry flows and deposits in the pond and forms a complex dam structure. Ore drawing parameters (e.g., slurry concentration and flow rate) have significant influence on the sedimentary structure of tailing dams. However, there is a lack of unified and quantitative understanding of the complicated effects of ore drawing parameters on the deposition behaviour of tailings. In the present study, flume tests were applied to investigate the characteristics of the sedimentary structure of tailing dams. Seven ore drawing experiments were conducted to simulate different slurry concentrations and flow rates. The distribution of characteristic particle sizes d50 and d10 of sediment was obtained. Furthermore, considering two dominant features of particle size distribution, a mathematical model for the equation between characteristic particle size and deposition distance was established. The exponential part of this equation describes the decreasing trend of the characteristic particle size, and a smooth step function is introduced to characterize the abrupt decrease in particle size. The experimental data of d50 and d10 in all these test cases can be approximated by the equation with correlation coefficients R2 greater than 0.861. As the slurry concentration of ore drawing increases, the hydraulic sorting gradually weakens. The characteristic particle size distribution curves corresponding to a larger flow rate are generally located above those corresponding to a small flow rate, indicating that the larger the flow rate is, the coarser the sediment. This study provided useful information for the determination of ore drawing parameters in actual tailing dams. The mathematical model of tailings’ particle size distribution can be further used for refined modelling of tailing dams, so as to analyse the safety and stability of the dams.

The extended Finite Element Method (XFEM) is derived from the traditional finite element method for discontinuous problems. It can simulate the behavior of cracks, which significantly improves the ability of finite element methods to simulate geotechnical and geological disaster problems. The integration of discontinuous enrichment functions in weak form and the ill-conditioning of the system equations are two major challenges in employing the XFEM in engineering applications. A mixed integration scheme is proposed in this paper to solve these problems. This integration scheme has a simple form and exhibits both the accuracy of the subcell integration method and the well-conditioning of a smeared integration method. The correctness and effectiveness of the proposed scheme were verified through a series of element analyses and two typical examples. For XFEM numerical simulations with unstructured meshes and arbitrary cracks/interfaces, this method guarantees the convergence of nonlinear iterations and yields correct results.

Four metal-ceramic composite coatings were prepared by laser cladding (LC) using Hastelloy C-276, nano-TiC and micro-TiB2 as raw materials to improve the surface properties and extend the service life of 316L stainless steel. The microstructure and mechanical properties were analyzed by metallographic microscopy, scanning electron microscopy (SEM), x-ray diffraction (XRD), Vickers hardness experiments, and friction and wear testing. The TiC and TiB2 phases were detected in the coating, exhibiting homogenous distribution as their content increased. As a result, the strengthening effect of the coating was enhanced, improving microhardness relative to that of the 316L substrate. The wear test revealed that the Hastelloy coating exhibited poor wear resistance, but the addition of TiC and TiB2 particles improved the wear resistance by reducing the wear rate. The lowest average coefficient and wear rate were attained at 50% and 70% ceramic contents, respectively. However, abundant hard particles on the surface easily fell off during the wear, which further impeded the surface degradation and increased the friction coefficient.

The effects of different levels of rutin (0, 0.05%, 0.1%, 0.2% and 0.3% w/v) and ethanol on the structure and gel properties of whey protein isolate (WPI) were examined. The results showed that the addition of ethanol promoted the gel formation of WPI. The addition of rutin increased the gel strength of WPI and maintained the water-holding capacity of the gel. Ethanol caused an increase in thiol content and surface hydrophobicity, but rutin decreased the thiol content and surface hydrophobicity of WPI. The particle size, viscosity and viscoelasticity of WPI increased at rutin levels of 0.2% and 0.3%, indicating that rutin caused cross-linking and aggregation of WPI, but rutin had no significant effect on the zeta-potential, indicating that electrostatic interactions were not the main force causing the changes in protein conformation and gel properties. Ethanol and rutin improved the gel properties of WPI possibly by inducing cross-linking of WPIs via hydrophobic and covalent interactions.

The gut microbiota is engaged in multiple interactions affecting host health, and gut dysbiosis can lead to many diseases. However, the effects of acetylcysteine (NAC) on the gut microbiome composition in pigs using metagenomic sequencing have not been reported. In this study, we used metagenome sequencing to study the effects of NAC on the pig gut microbiome. Sequencing results showed that microbial diversity was changed after NAC treatment. Antibiotic Resistance Genes Database (ARDB) analysis demonstrated that the main genes modified were macb, tsnr, norm, bl2be-per, vansb and pbp1b in the NAC group. Our data showed that NAC could affect microbial distribution at the phylum, gene and species levels. At the species level, NAC significantly increased the abundances of Megasphaera, Lactobacillus reuteri and Megasphaeraelsdenii and reduced the abundances of Phascolarctobacterium succinatutens, Prevotellacopri and Selenomonasbovis compared with the control group. In addition, Gene Ontology (GO) analysis revealed that in the NAC group, cellular process, metabolic process and single-organism process were the dominant terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that RNA transport, MAPK signaling pathway, cell cycle, glycosylphosphatidylinositol (GPI)-anchor biosynthesis and VEGF signaling pathway were the dominant signaling pathways in the NAC group. In conclusion, our results suggest that NAC may modify the piglet gut microbiome composition and these findings might provide a new strategy for maintaining animal and human health in the future.

Glaesserella parasuis (G. parasuis) can cause peritonitis in piglets. However, the pathogenesis of peritonitis remains unclear. Baicalin has been shown to possess anti-inflammatory and anti-oxidant functions. The aim of this study was to investigate the role of the PANX-1/P2X7 axis and the P2Y6 signaling pathway in peritonitis induced by G. parasuis and the effect of baicain on the PANX-1/P2X7 axis and P2Y6 pathway activation triggered by G. parasuis. A G. parasuis serovar 5 isolate SH0165 strain was obtained from the lungs of commercially produced pigs which had the typical symptoms of Glässer’s disease, namely arthritis, fibrinous polyserositis, hemorrhagic pneumonia, and meningitis. Then, 35 piglets were randomly divided into five groups, each group containing seven piglets. The groups consisted of a negative control group, an infection group, a 25 mg/kg baicalin group, a 50 mg/kg baicalin group, and a 100 mg/kg baicalin group. The results showed that G. parasuis could promote PANX-1/P2X7 axis and P2Y6 activation; induce NLRP3/caspase-1, IL-1β and IL-18 expression; trigger PLC/PKC and MLCK/MLC signaling activation; attenuate the expression of tight junction proteins ZO-1, E-cadherin, Occludins, and claudin 1; and stimulate CD14, CD24, CD36, CD47, and CD91 expression in the peritoneum as measured via Western blot (p < 0.01; PLC, p < 0.05). Baicalin could significantly inhibit PANX-1/P2X7 axis, P2Y6, and NLRP3/caspase-1 activation; reduce IL-1β and IL-18 expression; attenuate PLC/PKC and MLCK/MLC activation; promote ZO-1, E-cadherin, occludins, and claudin 1 expression; and reduce CD14, CD24, CD36, CD47, and CD91 expression in the peritoneum induced by G. parasuis as measured via Western blot. Our results deepen the understanding of the mechanism of peritonitis triggered by G. parasuis and provide some novel potential methods of controlling G. parasuis infection.

Glaesserella parasuis can induce endothelial barrier damage in piglets, although the mechanism by which this pathogen triggers inflammatory damage remains unclear. Baicalin possesses anti-inflammatory and anti-oxidant activities. However, whether baicalin can relieve endothelial barrier damage caused by Glaesserella parasuis infection has not yet been studied. Hence, we evaluated the ability of baicalin to counteract the changes induced by Glaesserella parasuis in porcine aortic vascular endothelial cells. The results showed that Glaesserella parasuis could upregulate the expression of pannexin 1 channel protein and promote the release of adenosine triphosphate, adenosine diphosphate, adenosine 3′-monophosphate, uridine triphosphate, uridine diphosphate, and uridine monophosphate in porcine aortic vascular endothelial cells. The expression level of purinergic receptor P2Y6 was upregulated in porcine aortic vascular endothelial cells triggered by Glaesserella parasuis. In addition, Glaesserella parasuis could activate phospholipase C-protein kinase C and myosin light chain kinase-myosin light chain signaling pathways in porcine aortic vascular endothelial cells. Baicalin could inhibit pannexin 1 channel protein expression, reduce adenosine triphosphate, adenosine diphosphate, adenosine 3′-monophosphate, uridine triphosphate, uridine diphosphate, and uridine monophosphate release, and attenuate the expression level of P2Y6 in porcine aortic vascular endothelial cells induced by Glaesserella parasuis. Baicalin could also reduce the activation of phospholipase C-protein kinase C and myosin light chain kinase-myosin light chain signaling pathways in porcine aortic vascular endothelial cells triggered by Glaesserella parasuis. Our study report that Glaesserella parasuis could promote pannexin 1 channel protein expression, induce nucleosides substance release, and P2Y6 expression in porcine aortic vascular endothelial cells and baicalin could inhibit the expression levels of pannexin 1, nucleosides substance, and P2Y6 in the porcine aortic vascular endothelial cells induced by Glaesserella parasuis, which might be served as some targets for treatment of inflammation disease caused by Glaesserella parasuis.

The gut microbiome exerts important functions on host health maintenance, whereas excessive antibiotic use may cause gut flora dysfunction resulting in serious disease and dysbiosis. Colistin is a broad-spectrum antibiotic with serious resistance phenomena. However, it is unclear whether colistin alters the gastrointestinal tract microbiome in piglets. In this study, 16s rDNA-based metagenome analyses were used to assess the effects of colistin on the modification of the piglet microbiome in the stomach, duodenum, jejunum, cecum, and feces. Both α- and β-diversity indices showed that colistin modified microbiome composition in these gastrointestinal areas. In addition, colistin influenced microbiome composition at the phylum and genus levels. At the species level, colistin upregulated Mycoplasma hyorhinis, Chlamydia trachomatis, Lactobacillus agilis, Weissella paramesenteroides, and Lactobacillus salivarius abundance, but downregulated Actinobacillus indolicus, Campylobacter fetus, Glaesserella parasuis, Moraxella pluranimalium, Veillonella caviae, Neisseria dentiae, and Prevotella disiens abundance in stomachs. Colistin-fed piglets showed an increased abundance of Lactobacillus mucosae, Megasphaera elsdenii DSM 20460, Fibrobacter intestinalis, and Unidentified rumen bacterium 12-7, but Megamonas funiformis, Uncultured Enterobacteriaceae bacterium, Actinobacillus porcinus, Uncultured Bacteroidales bacterium, and Uncultured Clostridiaceae bacterium abundance was decreased in the cecum. In feces, colistin promoted Mucispirillum schaedleri, Treponema berlinense, Veillonella magna, Veillonella caviae, and Actinobacillus porcinus abundance when compared with controls. Taken together, colistin modified the microbiome composition of gastrointestinal areas in piglets. This study provides new clinical rationalization strategies for colistin on the maintenance of animal gut balance and human public health.