Pathogenic diagnosis of lower respiratory tract infection has always been a clinical problem. The widespread application of metagenomic next-generation sequencing(mNGS)provides a rapid and accurate ...method for pathogenic diagnosis. However, how to interpret the results of mNGS detection, especially whether it has diagnostic value in detecting pathogens with low sequence number, has always puzzled clinicians. This paper discusses the definition of low sequence number (lower reads)detected by mNGS in lower respiratory tract infection, the cause of occurrence, the method to determine the reliability of the results, and how to correctly interpret the low sequence number report in combination with clinical practice. It is hoped that by comprehensively mastering the detection knowledge, the proper clinical analysis thinking can be established to improve the diagnostic ability of pathogens with low sequence number detected by mNGS in lower respiratory tract infection.
Chiral ketones have been shown to be effective organocatalysts for asymmetric epoxidation of olefins with broad substrate scope. High enantioselectivity has been obtained for a wide variety of trans ...and trisubstituted olefins, as well as a number of cis olefins, with encouragingly high ee's for some terminal olefins. The stereochemical outcome of the reaction can be rationalized by a spiro transition state model.
Hepatocellular carcinoma (HCC) is linked to inflammation and immunosuppression. Chemerin is highly expressed in the liver and implicated in the regulation of inflammation. However, the role of ...chemerin in HCC remains unclear. In this study, we aimed to investigate whether chemerin is able to influence HCC progression by regulating tumor-associated inflammation. Here we demonstrated that chemerin significantly decreased in blood and tumor tissues of HCC patients, and tumor chemerin levels were inversely associated with the prognosis. In an orthotopic mouse model of HCC, Rarres2
mice exhibited aggressive tumor growth and lung metastasis, whereas chemerin overexpression greatly inhibited tumor growth. The tumor-inhibitory effect of chemerin was accompanied by a shift in tumor-infiltrating immune cells from myeloid-derived suppressive cells (MDSCs) to interferon-γ
T cells and decreased tumor angiogenesis. Furthermore, we demonstrated that the tumor-inhibitory effect of chemerin was partly dependent on T cells, as chemerin overexpression could inhibit tumor growth, albeit to a lesser extent, in Rag1
mice when compared with wild-type controls. Mechanistically, chemerin inhibited nuclear factor-κB activation and the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-6) by tumor cells and tumor-associated endothelial cell, respectively, via its receptors, and consequently, MDSC induction was impaired, leading to restoration of antitumor T-cell response and decreased tumor angiogenesis. Clinically, systemic and tumor levels of chemerin were found to inversely correlate with circulating concentrations of GM-CSF or IL-6 and tumor-infiltrating myeloid cells, respectively, in HCC patients. Moreover, neutralization of GM-CSF and IL-6 abrogated HCC progression and MDSC accumulation in Rarres2
mice. In conclusion, our study reveals the tumor-inhibitory effect of chemerin by suppressing inflammatory tumor microenvironment with therapeutic implications for inflammation-associated cancer-like HCC.
Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, ...randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation.
Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety.
Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P < 0.001) and treatment-related AEs (54.1% versus 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group.
First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.
MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to direct widespread posttranscriptional gene repression. Although association with AGO typically protects miRNAs from nucleases, extensive ...pairing to some unusual target RNAs can trigger miRNA degradation. We found that this target-directed miRNA degradation (TDMD) required the ZSWIM8 Cullin-RING E3 ubiquitin ligase. This and other findings support a mechanistic model of TDMD in which target-directed proteolysis of AGO by the ubiquitin-proteasome pathway exposes the miRNA for degradation. Moreover, loss-of-function studies indicated that the ZSWIM8 Cullin-RING ligase accelerates degradation of numerous miRNAs in cells of mammals, flies, and nematodes, thereby specifying the half-lives of most short-lived miRNAs. These results elucidate the mechanism of TDMD and expand its inferred role in shaping miRNA levels in bilaterian animals.
By means of surface mechanical attrition treatment, nanometer-sized grains (with an average size of 30±5nm) were generated in the surface layer of a single-phase AZ91D alloy. Transmission electron ...microscopy investigations showed that the strain-induced grain refinement process in AZ91D alloy includes three steps. At the initial stage twinning dominates the plastic deformation and divides the coarse grains into finer twin platelets. With increasing strain, double twins and stacking faults form and a number of dislocation slip systems are activated, including basal plane systems, prismatic plane systems and pyramidal plane systems. As a result of the dislocation slip along these systems and of the cross slips, high-density dislocation arrays are formed which further subdivide the twin platelets into subgrains. Obvious evidence of dynamic recrystallization were identified within the high-strain-energy subgrains with a further increase of strain, leading to the formation of nano-sized grains in the surface layer.
Background
Metastasis-related in colon cancer 1 (MACC1) is highly expressed in a variety of solid tumours, but its role in pancreatic cancer (PC) remains unknown. Interferon gamma (IFN-γ) affecting ...MACC1 expression was explored as the potential mechanism following its intervention.
Methods
Expressions of MACC1 treated with IFN-γ gradient were confirmed by quantitative real-time PCR (qRT-PCR) and western blot (WB). Proliferation, migration, and invasion abilities of PC cells treated with IFN-γ were analysed by CCK8, EDU, colony formation, Transwell (with or without matrix gel) and wound-healing assays. Expression of antisense long non-coding RNA of MACC1, MACC1-AS1, and proteins of AKT/mTOR pathway, (pho-)AKT, and (pho-)mTOR was also assessed by qRT-PCR and WB. SiRNA kit and lentiviral fluid were conducted for transient expression of MACC1 and stable expression of MACC1-AS1, respectively. Rescue assays of cells overexpressing MACC1-AS1 and of cells silencing MACC1 were performed and cellular properties and proteins were assessed by the above-mentioned assays as well.
Results
IFN-γ inhibited MACC1 expression in a time- and dose-dependent manner; 100 ng/mL IFN-γ generally caused downregulation of most significant (
p
≤ 0.05). In vitro experiments revealed that IFN-γ decreased cellular proliferation, migration, and invasion abilities and downregulated the expression of pho-AKT and pho-mTOR (
p
≤ 0.05). Conversely, overexpression of MACC1-AS1 upregulated pho-AKT and pho-mTOR proteins, and reversed cellular properties (
p
≤ 0.05). Rescue assays alleviated the above changes of pho-AKT/ mTOR and cellular properties.
Conclusion
IFN-γ affected PC properties by MACC1-AS1/MACC1 axis via AKT/mTOR signaling pathway, which provides novel insight for candidate targets for treating PC.
Discovery of magnetic Weyl fermions: Dirac fermions split into pairs of Weyl fermions by slow magnetic fluctuations.
Weyl fermions as emergent quasiparticles can arise in Weyl semimetals (WSMs) in ...which the energy bands are nondegenerate, resulting from inversion or time-reversal symmetry breaking. Nevertheless, experimental evidence for magnetically induced WSMs is scarce. Here, using photoemission spectroscopy, we observe that the degeneracy of Bloch bands is already lifted in the paramagnetic phase of EuCd
2
As
2
. We attribute this effect to the itinerant electrons experiencing quasi-static and quasi–long-range ferromagnetic fluctuations. Moreover, the spin-nondegenerate band structure harbors a pair of ideal Weyl nodes near the Fermi level. Hence, we show that long-range magnetic order and the spontaneous breaking of time-reversal symmetry are not essential requirements for WSM states in centrosymmetric systems and that WSM states can emerge in a wider range of condensed matter systems than previously thought.
•Developed a 96-well plate method for determining apparent amylose content.•The new methodology uses two wavelengths for analysis.•Results are very similar to existing amylose determination ...methods.•Capable of analyzing over 50 samples in replicate per day.
Cereal starch amylose/amylopectin (AM/AP) is critical in functional properties for food and industrial applications. Conventional methods of AM/AP are time consuming and labor intensive making it difficult to screen the large sample sets necessary for evaluating breeding samples and investigating environmental impact on starch development. The objective was to adapt and optimize the iodine binding assay in a 96-well plate format for measurement at both λ 620nm and λ 510nm. The standard curve for amylose content was scaled to a 96-well plate format and demonstrated R2 values of 0.999 and 0.993 for single and dual wavelengths, respectively. The plate methods were applicable over large ranges of amylose contents: high amylose maize starch at 61.7±2.3%, normal wheat starch at 29.0±0.74%, and a waxy maize starch at 1.2±0.9%. The method exhibited slightly greater amylose content values than the Concanavalin A method for normal type starches; but is consistent with cuvette scale iodine binding assays.
PDF
