Circ_SETD3 regulates gefitinib sensitivity and tumor progression by miR-873-5p-dependent regulation of APPBP2 in non-small cell lung cancer

Previous data have shown the prominent clinical efficacy of gefitinib in non-small cell lung cancer (NSCLC) patients. However, its therapeutic efficacy is limited because of the development of gefitinib resistance. This research is designed to investigate the role of circRNA SET domain containing 3, actin histidine (circ_SETD3) in the sensitivity of NSCLC to gefitinib. The expression of circ_SETD3, microRNA-873-5p (miR-873-5p) and amyloid protein-binding protein 2 (APPBP2) was detected by qRT-PCR. Protein expression was determined by western blot analysis or immunohistochemistry assay. The half-maximal inhibitory concentration of gefitinib was determined by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation was investigated by 5-Ethynyl-29-deoxyuridine (EdU), cell colony formation and MTT assays. Cell apoptosis was analyzed by Annexin V-fluorescein isothiocyanate and propidium iodide double staining assay. Transwell assay was employed to evaluate cell migration and invasion. Additionally, the binding relationship between miR-873-5p and circ_SETD3 or APPBP2 was predicted by starbase online database, and identified by a dual-luciferase reporter assay. Further, circ_SETD3 silencing-mediated effect on tumor sensitivity to gefitinib in vivo was confirmed by xenograft mouse model experiment. Circ_SETD3 and APPBP2 expression were upregulated, while miR-873-5p was downregulated in gefitinib-resistant NSCLC tissues and cells compared with gefitinib-sensitive NSCLC tissues or cells. Reduced expression of circ_SETD3 repressed gefitinib resistance, proliferation, migration and invasion, but induced apoptosis of gefitinib-resistant NSCLC cells. Additionally, circ_SETD3 modulated gefitinib sensitivity and tumor development by binding to miR-873-5p. APPBP2 upregulation attenuated miR-873-5p-mediated gefitinib sensitivity and NSCLC progression. Furthermore, circ_SETD3 absence improved tumor sensitivity to gefitinib in vivo. Circ_SETD3 knockdown improved gefitinib sensitivity and repressed NSCLC cell malignancy via miR-873-5p/APPBP2 axis, which provides a theoretical basis for using circ_SETD3-based therapeutic strategies to improve NSCLC sensitivity to gefitinib.</p

Oxidation−Crystallization Process of Colloids: An Effective Approach for the Morphology Controllable Synthesis of SnO₂ Hollow Spheres and Rod Bundles

In this article, we have demonstrated that the oxidation−crystallization method of amorphous colloids in the microreactor systems generated by soft templates is convenient and feasible in the large-scale production of hollow and one-dimensional (1D) structures. Through the air oxidation and crystallization of colloidal spheres in the different systems, SnO2 hollow spheres and rod bundles, respectively, were controllably obtained. The detailed growth processes of SnO2 hollow spheres and rod bundles were investigated. When SnO2 hollow spheres and rod bundles were used as an anode material for lithium-ion batteries, they exhibited relatively high electrochemical capacities. Thus, it is rational to expect that this simple method can be extended to systems of other inorganic materials with desired morphologies

A Bioorthogonal Ligation Enabled by Click Cycloaddition of <i>o</i>‑Quinolinone Quinone Methide and Vinyl Thioether

There is an increasing interest in the use of bioorthogonal ligation to advance biomedical research through selective labeling of biomolecules in living systems. Accordingly, discovering new reactions to expand the toolbox of bioorthogonal chemistry is of particular interest to chemical biologists. Herein we report a new bioorthogonal ligation enabled by click hetero-Diels–Alder (HDA) cycloaddition of in situ-generated <i>o</i>-quinolinone quinone methides and vinyl thioethers. This reaction is highly selective and proceeds smoothly under aqueous conditions. The functionalized vinyl thioethers are small and chemically stable in vivo, making them suitable for use as bioorthogonal chemical reporters that can be effectively coupled to various biomolecules. We utilized this bioorthogonal ligation for site-specific labeling of proteins as well as imaging of bioactive small molecules inside live cells

Breakdown of Maxwell Garnett theory due to evanescent fields at deep-subwavelength scale

Deep-subwavelength all-dielectric composite materials are believed to tightly obey the Maxwell Garnett effective medium theory. Here, we demonstrate that the Maxwell Garnett theory could break down due to evanescent fields in deep-subwavelength dielectric structures. By utilizing two- and three-dimensional dielectric composite materials with inhomogeneities at the scale of {\lambda}/100, we show that local evanescent fields generally occur nearby the dielectric inhomogeneities. When tiny absorptive constituents are placed there, the absorption and transmission of the whole composite will show strong dependence on the positions of the absorptive constituents. The Maxwell Garnett theory fails to predict such position-dependent characteristics, because it averages out the evanescent fields. By taking the distribution of the evanescent fields into consideration, we made a correction to the Maxwell Garnett theory, such that the position-dependent characteristics become predictable. We reveal not only the breakdown of the Maxwell Garnett theory, but also a unique phenomenon of "invisible" loss induced by the prohibition of electric fields at deep-subwavelength scales. Our work promises a route to control the macroscopic properties of composite materials without changing their composition, which is beyond the traditional Maxwell Garnett theory

Additional file 2: of Laparoscopy versus open appendectomy for elderly patients, a meta-analysis and systematic review

NOS scale for enrolled studies. (DOCX 15 kb

Additional file 1: of Laparoscopy versus open appendectomy for elderly patients, a meta-analysis and systematic review

Searching Terms in MEDLINE. (DOCX 12 kb

Additional file 2 of Clinical and genetic characterization of a large cohort of patients with Wilson’s disease in China

Additional file 2: Table S2. Details of potential pathogenic variants of ATP7B identified in this study

Additional file 1 of Clinical and genetic characterization of a large cohort of patients with Wilson’s disease in China

Additional file 1: Table S1. Primers used for amplification and sequencing of exons and exon–intron boundaries of ATP7B

Additional file 5 of Clinical and genetic characterization of a large cohort of patients with Wilson’s disease in China

Additional file 5: Table S4. ATP7B variant combinations in this cohort

Additional file 4 of Clinical and genetic characterization of a large cohort of patients with Wilson’s disease in China

Additional file 4: Fig. S1. Sequencing results for 64 novel missense variants of the ATP7B gene. Fig. S2. Sequencing results for novel variants of the ATP7B gene except for missense variants. Fig. S3. Homology comparisons of novel missense variants in the ATP7B protein