Long-Term Erythromycin Treatment Alters the Airway and Gut Microbiota: Data from Chronic Obstructive Pulmonary Disease Patients and Mice with Emphysema.

INTRODUCTION: Although long-term macrolide antibiotics could reduce the recurrent exacerbation of chronic obstructive pulmonary disease (COPD), the side effect of bacterial resistance and the impact on the microbiota remain concerning. We investigated the influence of long-term erythromycin treatment on the airway and gut microbiota in mice with emphysema and patients with COPD. METHODS: We conducted 16S rRNA gene sequencing to explore the effect of erythromycin treatment on the lung and gut microbiota in mice with emphysema. Liquid chromatography-mass spectrometry was used for lung metabolomics. A randomized controlled trial was performed to investigate the effect of 48-week erythromycin treatment on the airway and gut microbiota in COPD patients. RESULTS: The mouse lung and gut microbiota were disrupted after cigarette smoke exposure. Erythromycin treatment depleted harmful bacteria and altered lung metabolism. Erythromycin treatment did not alter airway or gut microbial diversity in COPD patients. It reduced the abundance of pathogens, such as Burkholderia, in the airway of COPD patients and increased levels of symbiotic bacteria, such as Prevotella and Veillonella. The proportions of Blautia, Ruminococcus, and Lachnospiraceae in the gut were increased in COPD patients after erythromycin treatment. The time to the first exacerbation following treatment was significantly longer in the erythromycin treatment group than in the COPD group. CONCLUSION: Long-term erythromycin treatment reduces airway and gut microbe abundance in COPD patients but does not affect microbial diversity and restores microbiota balance in COPD patients by reducing the abundance of pathogenic bacteria.

Dynamic Characteristics of Plasma in Ultrasonic-Assisted Narrow-Gap Laser Welding with Filler Wire.

Laser welding with filler wire was applied to Q345D in a narrow gap under ultrasonic assistance, and the dynamic characteristics of plasma were studied by high-speed imaging and spectral acquisition. The results showed that the plasma area decreased gradually with increasing distance between the ultrasonic loading position and welding seam. The electron density and temperature of the plasma with ultrasonic assistance were higher than those without ultrasound. The electron density was approximately 1016~1017 cm-3, and the plasma temperature was approximately 4000~6000 K. Ultrasonic assisted laser wire filling welding can bring about cavitation effect and significantly reduce the porosity problem.

LINC00152 knockdown suppresses tumorigenesis in non-small cell lung cancer via sponging miR-16-5p.

Background: Non-small cell lung cancer (NSCLC) is one of the most aggressive types of cancer worldwide. It has been reported that long non-coding RNAs (lncRNAs) are involved in the pathogenesis of NSCLC. In addition, LINC00152 is known to be upregulated in NSCLC. However, the mechanism underlying the effect of LINC00152 on NSCLC tumorigenesis remains to be elucidated. Methods: In the present study, cell viability, apoptosis and invasion were investigated by CCK-8, flow cytometry and Transwell assays, respectively. Reverse transcription­quantitative polymerase chain reaction and Western blotting were performed to determine the mRNA and protein expression levels. In addition, the association between LINC00152, microRNA (miR)-16-5p and BCL2-like 2 (BCL2L2) was evaluated using a dual-luciferase assay. Results: The results demonstrated that LINC00152-knockdown significantly attenuated the viability of NSCLC cells via promoting cell apoptosis. In addition, the migration and invasion ability of NSCLC cells was also decreased following transfection of cells with LINC00152 siRNA. Furthermore, miR-16-5p inhibitor or BCLCL2-overexpression reversed LINC00152 siRNA-induced NSCLC cell growth inhibition. Conclusions: The findings of the present study demonstrated that LINC00152-silencing suppressed NSCLC tumorigenesis via regulating the miR-16-5p/BCL2L2 axis. Therefore, linc00152 has the potential as a molecular marker and may be a potential target for the treatment of non-small cell lung cancer.

Insight into the Catalytic Activity of Amorphous Multimetallic Catalysts under a Magnetic Field toward the Oxygen Evolution Reaction.

Slow kinetics in the oxygen evolution reaction (OER) remains a Gordian knot to develop an efficient and cost-effective electrocatalyst in electrochemical water splitting. In recent studies, either a synergistic effect on multimetallic catalysts or spin polarization in ferromagnetic materials is considered as a desirable way to improve water electrolysis. Herein, the OER performance of amorphous FeNiCo-based multimetallic catalysts with adjustable composition was investigated from the perspective of atomic structure. Mössbauer spectra results demonstrate that the OER activities exhibit a significant dependence on the local structure of catalysts in which a catalyst with a high content of Fe clusters of low coordination numbers tends to obtain higher activity. Furthermore, benefiting from the spin polarization of these ferromagnetic catalysts, the OER activity is notably enhanced in the presence of a magnetic field. In particular, overpotential reduction exceeding 20 mV (above 100 mA cm-2) in alkaline OER performance is observed for strong ferromagnetic catalysts in comparison with the weak ferromagnetic ones. An increment of 65.2% in turnover frequency is achieved for the catalyst with the strongest ferromagnetism. This magnetic enhancement strategy affords an effective way of improving the water oxidation performance on amorphous ferromagnetic catalysts.

The functional activity of donor kidneys is negatively regulated by microribonucleic acid-451 in different perfusion methods to inhibit adenosine triphosphate metabolism and the proliferation of HK2 cells.

This study explored the regulation of different perfusion methods on ischemia-reperfusion injury in donor kidneys. In this study, renal cortical/medullary tissue specimens were collected from porcine kidneys donors using different perfusion methods at various time points. Hematoxylin and eosin (H&E) staining was used to test the histological differences. Differentially expressed micro-ribonucleic acids (miRNAs) were identified by miRNA transcriptome sequencing. Reverse transcription-polymerase chain reaction (RT-PCR) tests were used to verify the changes in miRNAs in the kidney tissue taken from different perfusion groups. The related signaling pathways and the changes in the cell functions of different perfusion groups were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) /Gene Ontology (GO) bioinformatics analyses. The effects of miRNA overexpression on the metabolism and proliferation of HK2 cells were detected by ATP kit and MTT assay. The H&E staining results showed that there were essentially no differences in the tissue samples among different perfusion groups at and before 12 h compared with a control group. The quantitative PCR results revealed that there was essentially no change in the expression of ssc-miR-451, ssc-miR-1285, and ssc-miR-486 in the cis infusion or joint infusion kidney groups, and their expression was significantly down-regulated over time in the trans-infusion kidney group. The bioinformatics analysis showed that the cellular component, molecular function, and biological processes of the kidney tissue, which had been perfused using three methods, had been consistently affected. The most significant changes after perfusion occurred in the intracellular metabolism signaling pathways. Furthermore, the energy metabolism and proliferation of the HK2 cells were significantly inhibited after the overexpression of miR-451. Specific miRNA markers, such as miR-451, may play a negative regulatory role in cell metabolism following the perfusion of kidney transplants using different methods.

Screening and Identification of Hub Genes in the Corticosteroid Resistance Network in Human Airway Epithelial Cells via Microarray Analysis.

Background and Objective: Corticosteroid resistance is a major barrier to chronic obstructive pulmonary disease (COPD), but the exact mechanism of corticosteroid resistance in COPD has been less well studied. Methods: The microarray dataset GSE11906, which includes genomic and clinical data on COPD, was downloaded from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) were identified using R software. Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes (KEGG) were utilized to enrich and analyze the gene cohort related to the response to steroid hormones, respectively. The Connectivity Map (CMap) database was used to screen corticosteroid resistance-related drugs that might exert a potential therapeutic effect. STRING was used to construct a protein-protein interaction (PPI) network of the gene cohort, and the CytoHubba plug-in of Cytoscape was used to screen the hub genes in the PPI network. The expression levels of hub genes in cigarette smoke extract (CSE)-stimulated bronchial epithelial cells were assayed by quantitative real-time PCR and western blotting. Results: Twenty-one genes were found to be correlated with the response to steroid hormones. In the CMap database, 32 small-molecule compounds that might exert a therapeutic effect on corticosteroid resistance in COPD were identified. Nine hub genes were extracted from the PPI network. The expression levels of the BMP4, FOS, FN1, EGFR, and SPP1 proteins were consistent with the microarray data obtained from molecular biology experiments. Scopoletin significantly restrained the increases in the levels of AKR1C3, ALDH3A1, FN1 and reversed the decreases of phosphorylated GR and HDAC2 caused by CSE exposure. Conclusion: The BMP4, FOS, FN1, EGFR, and SPP1 genes are closely correlated with CSE-induced glucocorticoid resistance in airway epithelial cells. Scopoletin may be a potential drug for the treatment of glucocorticoid resistance caused by CSE.

Analysis of Development Mechanism of Giant Cell Arteritis in Nude Mouse Model through Color Duplex Sonography and Computerized Tomography Nanocontrast Agent.

To explore the application value of color duplex sonography and enhanced computerized tomography (CT) inspection based on a nanocontrast agent in diagnosis and pathogenesis in giant cell arteritis (GCA), the GCA nude mouse model was constructed. In this study, 40 healthy male BalB/c nude mice aged 6-8 weeks were randomly divided into a control group (no model) and an experimental group (model), with 20 mice in each group, and the temporal artery tissue of GCA patients diagnosed as positive by temporal artery biopsy was implanted into nude mice to construct a GCA nude mouse model. Abdominal aortic biopsy and immunohistochemistry were used to verify the success of the GCA nude mouse model. All nude mice were subjected to color duplex sonography and enhanced CT examination based on a nanocontrast agent. At the same time, the basic indicators such as body weight, temperature, white blood cell (WBC), lymphocytes (LYM), hemoglobin (HGB), and platelet (PLT) were measured, and the protein expression levels of interleukin-6 (IL-6) and signal transducer and activator of transcription 3 (STAT3) were detected by immunohistochemistry. The results showed that the temporal artery wall of the nude mice in the experimental group thickened and the lumen was significantly narrowed, indicating that the cell arteritis model of nude mice was successfully constructed; ultrasound examination showed that the right superficial temporal artery vascular cavity narrowed, the blood flow signal changed like a filling defect around the periphery, and there was a low echo halo. CT examination showed that the left superficial temporal artery narrowed, and the inner diameter of the narrow segment of blood vessels changed like a bead. The body weight of nude mice in the experimental group decreased significantly after the modeling was completed (P < 0.05); after modeling, the body temperature of the nude mice in the experimental group increased significantly (P < 0.05); LYM and HGB values of nude mice in the experimental group were significantly lower than those in the control group (P < 0.05); the content of IL-6, STAT3, IL-6, and STAT3 proteins in the arterial tissue of nude mice in the experimental group was lower than that of the control group (P < 0.05), indicating that color duplex sonography and CT contrast agent technology can be used in the diagnosis and development mechanism research of GC.