Characterization on Crack Initiation and Early Propagation Region of Nickel-Based Alloys in Very High Cycle Fatigue

As nickel-based alloys are more and more widely used in engineering fields for bearing cyclic loadings, it is necessary to study their very-high-cycle fatigue (VHCF) properties. In this paper, the fatigue properties of nickel-based alloy 625 were investigated using an ultrasonic fatigue test apparatus. The fracture microscopy shows that around the crack initiation site there are two characteristic zones, a rough area (RA) and a fine granular area (FGA). Inclusions caused the interior fatigue crack initiation, and the coalescence of neighboring micro cracks was strongly influenced by the local microstructure, resulting in the RA morphology. Subsequently, the contact and compressing of the crack surfaces contributed to the formation of the FGA. Finally, the stress intensity factors of the RA and FGA were quantitatively evaluated for further discussion of the crack initiation and propagation processes

Nuclear protein 1 promotes unfolded protein response during endoplasmic reticulum stress, and alleviates apoptosis induced by cisplatin in non-small cell lung cancer cells

Purpose: To investigate the role of nuclear protein 1 (NUPR1) in the drug resistance of non-small cell lung cancer (NSCLC) and its regulatory mechanisms. Methods: Quantitative polymerase chain reaction (qPCR) and immunoblot assays were conducted to determine NUPR1 expression in A549 cells. Cisplatin sensitivity and cisplatin-induced apoptosis were investigated in NUPR1 knockdown or overexpressed cells via 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and flow cytometry. The potential association between unfolded protein response (UPR) and NUPR1 levels in response to cisplatin were explored. The effect of endoplasmic reticulum (ER) stress on apoptosis was examined using flow cytometry. Results: Cisplatin treatment promoted the expression of NUPR1 in NSCLC cells. NUPR1 regulated cisplatin resistance in NSCLC and also regulated UPR in ER stress induced by cisplatin. The results show NUPR1 regulated apoptosis induced by ER stress following tunicamycin treatment. Conclusion: NSCLC cells may promote the UPR in ER stress by promoting the expression of NUPR1, thereby reducing the ER stress induced by cisplatin

Comparison of the NG-Test Carba 5, Colloidal Gold Immunoassay (CGI) Test, and Xpert Carba-R for the Rapid Detection of Carbapenemases in Carbapenemase-Producing Organisms

Carbapenem-resistant Enterobacterales (CRE) are increasingly recognized as an urgent public health concern. The rapid and accurate identification of carbapenemases could provide insights into antimicrobial therapy and infection control. In this study, we evaluated the efficacy of three different methods, including the NG-test Carba 5, colloidal gold immunoassay (CGI) test, and Xpert Carba-R assay, for the rapid detection of five carbapenemases (KPC, NDM, IMP, OXA-48, and VIM). A total of 207 Gram-negative strains collected from patients and hospital sewages were tested. The presence or absence of carbapenemase genes in the whole-genome sequences was used as the gold standard for evaluating the accuracy of the above-mentioned three methods. Among the 192 strains carrying only one carbapenemase gene, the accuracies of the NG-Test Carba 5, CGI test, and Xpert Carba-R were 96.88% (95% CI, 93.01–98.72%), 96.88% (95% CI, 93.01–98.72%), and 97.92% (95% CI, 94.41–99.33%), respectively. Xpert Carba-R was able to detect all 13 types of KPC variants, including KPC-2, KPC-3, KPC-25, KPC-33, KPC-35, KPC-51, KPC-52, KPC-71, KPC-76, KPC-77, KPC-78, KPC-93, and KPC-123, with a detection sensitivity of 100.00% (95% CI, 96.50–100.00%), a specificity of 100.00% (95% CI, 92.38–100.00%), and a κ index of 1.00. For IMP, Carba 5 was superior to the other two methods, with a sensitivity of 100% (95% CI, 71.66–100.00%), a specificity of 100% (95% CI, 97.38–100.00%), and a κ index of 1.00. For the remaining 15 strains carrying two or three kinds of carbapenemase genes, Carba 5 performed the best, which accurately identified all the target genes, followed by Xpert Carba-R (12/15, 80.00%) and the CGI test (10/15, 66.67%). Therefore, all three assays demonstrated reliable performances in carbapenemase detection, and Xpert Carba-R should be recommended for the detection of KPC variants, especially for patients at a high risk of infections caused by ceftazidime/avibactam-resistant strains. IMPORTANCE: CRE was listed as one of the top three pathogens that are in critical need of new antibiotics by the WHO. The rapid and accurate identification of carbapenemases is important for antimicrobial therapy and infection control. In recent years, new beta-lactam/beta-lactamase inhibitor combinations such as ceftazidime/avibactam (CZA) have been approved by the Food and Drug Administration (FDA) to cope with CRE challenges. CZA was effective against class A, class C, and some class D enzymes such as OXA-48-like. However, CZA-resistant KPC variants emerged at an alarming speed, which posed a new challenge for the accurate identification of KPC variants. In this study, we evaluated the performance of two lateral flow immunochromatographic assays, namely, NG-test Carba 5 and the CGI test, and the automated real-time quantitative PCR Xpert Carba-R in the rapid detection of carbapenemases. Notably, 13 types of KPC variants were enrolled in this study, which covered most KPC variants discovered in China. Carba-R was superior to NG-teat Carba 5 and the CGI test; it was able to detect all of the included KPC variants, including KPC-2, KPC-3, KPC-25, KPC-33, KPC-35, KPC-51, KPC-52, KPC-71, KPC-76, KPC-77, KPC-78, KPC-93, and KPC-123

Comparison of the NG-Test Carba 5, Colloidal Gold Immunoassay (CGI) Test, and Xpert Carba-R for the Rapid Detection of Carbapenemases in Carbapenemase-Producing Organisms

Carbapenem-resistant Enterobacterales (CRE) are increasingly recognized as an urgent public health concern. The rapid and accurate identification of carbapenemases could provide insights into antimicrobial therapy and infection control. In this study, we evaluated the efficacy of three different methods, including the NG-test Carba 5, colloidal gold immunoassay (CGI) test, and Xpert Carba-R assay, for the rapid detection of five carbapenemases (KPC, NDM, IMP, OXA-48, and VIM). A total of 207 Gram-negative strains collected from patients and hospital sewages were tested. The presence or absence of carbapenemase genes in the whole-genome sequences was used as the gold standard for evaluating the accuracy of the above-mentioned three methods. Among the 192 strains carrying only one carbapenemase gene, the accuracies of the NG-Test Carba 5, CGI test, and Xpert Carba-R were 96.88% (95% CI, 93.01–98.72%), 96.88% (95% CI, 93.01–98.72%), and 97.92% (95% CI, 94.41–99.33%), respectively. Xpert Carba-R was able to detect all 13 types of KPC variants, including KPC-2, KPC-3, KPC-25, KPC-33, KPC-35, KPC-51, KPC-52, KPC-71, KPC-76, KPC-77, KPC-78, KPC-93, and KPC-123, with a detection sensitivity of 100.00% (95% CI, 96.50–100.00%), a specificity of 100.00% (95% CI, 92.38–100.00%), and a κ index of 1.00. For IMP, Carba 5 was superior to the other two methods, with a sensitivity of 100% (95% CI, 71.66–100.00%), a specificity of 100% (95% CI, 97.38–100.00%), and a κ index of 1.00. For the remaining 15 strains carrying two or three kinds of carbapenemase genes, Carba 5 performed the best, which accurately identified all the target genes, followed by Xpert Carba-R (12/15, 80.00%) and the CGI test (10/15, 66.67%). Therefore, all three assays demonstrated reliable performances in carbapenemase detection, and Xpert Carba-R should be recommended for the detection of KPC variants, especially for patients at a high risk of infections caused by ceftazidime/avibactam-resistant strains. IMPORTANCE: CRE was listed as one of the top three pathogens that are in critical need of new antibiotics by the WHO. The rapid and accurate identification of carbapenemases is important for antimicrobial therapy and infection control. In recent years, new beta-lactam/beta-lactamase inhibitor combinations such as ceftazidime/avibactam (CZA) have been approved by the Food and Drug Administration (FDA) to cope with CRE challenges. CZA was effective against class A, class C, and some class D enzymes such as OXA-48-like. However, CZA-resistant KPC variants emerged at an alarming speed, which posed a new challenge for the accurate identification of KPC variants. In this study, we evaluated the performance of two lateral flow immunochromatographic assays, namely, NG-test Carba 5 and the CGI test, and the automated real-time quantitative PCR Xpert Carba-R in the rapid detection of carbapenemases. Notably, 13 types of KPC variants were enrolled in this study, which covered most KPC variants discovered in China. Carba-R was superior to NG-teat Carba 5 and the CGI test; it was able to detect all of the included KPC variants, including KPC-2, KPC-3, KPC-25, KPC-33, KPC-35, KPC-51, KPC-52, KPC-71, KPC-76, KPC-77, KPC-78, KPC-93, and KPC-123

Platinum single-atom catalyst coupled with transition metal/metal oxide heterostructure for accelerating alkaline hydrogen evolution reaction

While H2 evolution from water may represent a renewable energy source, there is a strong need to improve catalytic efficiencies while maximizing materials utilization. Here, authors examine single-atom Pt on nickel-based heterostructures as highly active electrocatalysts for alkaline H2 evolution

Arctigenin Induces an Activation Response in Porcine Alveolar Macrophage Through TLR6-NOX2-MAPKs Signaling Pathway

Arctigenin (ARG), one of the most active ingredients abstracted from seeds of Arctium lappa L., has been proved to exert promising biological activities such as immunomodulatory, anti-viral, and anti-cancer etc. However, the mechanism behind its immunomodulatory function still remains elusive to be further investigated. In this study, we found that ARG had no significant effects on the cell proliferation in both porcine alveolar macrophage cell line (3D4/21) and primary porcine derived alveolar macrophage. It remarkably increased the expression and secretion of the two cytokines including tumor necrosis factor-alpha (TNF-α) and transforming growth factor beta1 (TGF-β1) in a dose-dependent manner with the concomitant enhancement of phagocytosis, which are the indicators of macrophage activation. ARG also elevated the intracellular reactive oxygen species (ROS) production by activating NOX2-based NADPH oxidase. Furthermore, inhibition of ROS generation by diphenyliodonium and apocynin significantly suppressed ARG-induced cytokine secretion and phagocytosis increase, indicating the requirement of ROS for the porcine alveolar macrophage activation. In addition, TLR6-My88 excitation, p38 MAPK and ERK1/2 phosphorylation were all involved in the process. As blocking TLR6 receptor dramatically attenuated the NOX2 oxidase activation, cytokine secretion and phagocytosis increase. Inhibiting ROS generation almost abolished p38 and ERK1/2 phosphorylation, and the cytokine secretion could also be remarkably reduced by p38 and ERK1/2 inhibitors (SB203580 and UO126). Our finding gave a new insight of understanding that ARG could improve the immune-function of porcine alveolar macrophages through TLR6-NOX2 oxidase-MAPKs signaling pathway