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Cerium dioxide (CeO2) nanocatalysts were initially grown in situ on 2D graphitic carbon nitride (g-C3N4) nanosheets to yield the nanocomposites g-C3N4/CeO2 with a spherical structure for the catalysis-based colorimetric analysis of Hg2+ ions in blood and wastewater. As the synergetic introduction of g-C3N4 nanosheets might promote the electron transfer in CeO2, the resulting g-C3N4/CeO2 nanozyme was found to present greatly enhanced catalytic activity, as demonstrated by the steady-state kinetic studies, which is nearly 4-fold higher than that of pure CeO2. Moreover, the g-C3N4/CeO2 nanozymes would aggregate in the presence of Hg2+ ions due to the strong interaction between Hg2+ and the nitrogen of g-C3N4, leading to a decrease of catalysis rationally depending on the Hg2+ ion concentration. A colorimetric analysis strategy is therefore developed for the selective detection of Hg2+ ions separately in the complex samples of blood and wastewater, showing a linear concentration range from 0.50 nM to 800 nM with the LOD of 0.23 nM as exemplified for Hg2+ ions in blood. Also, the recovery tests indicated that the developed colorimetric method can allow for the accurate analysis of Hg2+ ions in wastewater and blood. Such a route for the fabrication of composite nanozymes by growing catalytic nanomaterials on conductive 2D substrates may be extended to the design of other kinds of nanozymes with enhanced catalytic performances for developing catalysis-based detection platforms.

Background: Tropomyosin 4 (TPM4) is a member of the tropomyosin family of actin-binding proteins. Abnormal level of TPM4 is found in several cancers, and TPM4 is considered as a potential detecting marker for ovarian cancer, breast cancer, colon cancer, keratoacanthoma and esophageal squamous cell carcinoma. In this paper, the function of TPM4 in lung cancer cell lines was determined. Materials and methods: TPM4 knockout cells were constructed by CRISPR/CAS9 technique. TPM4 overexpression cells were also constructed based on TPM4 knockout cells. Cell growth ability was detected by MTS assay. The potency of cell motility was investigated using transwell assay and wound scratch assay. The protein levels in lung cancer cells were determined by western-blot. Immunofluorescence technique was used to image the structure of F-actin. Results: As a result, TPM4 downregulation and TPM4 upregulation cell models were obtained successfully. Cell motility was inhibited by the suppression of TPM4 while cell migration was enhanced in TPM4 upregulated cells. But TPM4 was not involved in cell proliferation and EMT progression. Microfilaments were depolymerized result from the suppression of TPM4 expression. And F-actin assembly was increased when TPM4 was upregulated. Conclusion: In summary, TPM4 was able to promote cell motility by altering the actin cytoskeleton directly.

Combining photodynamic therapy (PDT) and immunotherapy has shown profound impact for synergistic treatment of malignant tumors. However, the shallow penetration depth of the traditional visible light activated PDT, immunosuppressive tumor microenvironment (TME), and poor immunogenicity of deep-seated solid tumors have significantly impeded the therapeutic efficiency. Herein, a soft X-ray activated nanoprobe is rationally engineered via integrating porphyrin Zr-based metal-organic framework with lanthanide NaYF4 :Gd,Tb@NaYF4 scintillator nanoparticles (SNPs) by a new in situ growth strategy for synergistic PDT and immunotherapy of tumor. The nanoprobe possesses remarkably enhanced reactive oxygen species (ROS) generation triggered by soft X-ray via further covalently grafting rose bengal on the nanoprobe, even at tissue depths of 3 cm. Moreover, the soft X-ray induced ROS can act as potential immunogenic cell death (ICD) trigger, subsequently leading to the activation of the adaptive antitumor immune-response. Significantly, the boosted ROS generation can further modulate the immunosuppressive TME. This work provides new strategy of designing antitumor nanoprobes for soft X-ray triggered deep-tissue PDT and immune response, breaking the depth barriers suffered by the traditional photoactivated PDT or ICD using visible and near infrared light.

Cyclin Y (CCNY) is a novel cyclin and highly conserved in metazoan species. Previous studies from our and other laboratory indicate that CCNY play a crucial role in tumor progression. There are two CCNY isoform which has different subcellular distributions, with cytoplasmic isoform (CCNYc) and membrane distribution isoform (CCNYm). However, the expression and function of CCNY isoforms is still unclear. We firstly found CCNYc was expressed in natural lung cancer tissue and cells through the subcellular distribution. Co-IP and immunofluorescence showed that both CCNYm and CCNYc could interact with PFTK1. Further studies illustrated that CCNYc but not CCNYm enhanced cell migration and invasion activity bothin vivoand vitro. The function of CCNYc could be inhibited by suppression of PFTK1 expression. In addition, our data indicated that tropomyosin 4 (TPM4), a kind of actin-binding proteins, was down-regulated by suppression of CCNY. F-actin assembly could be controlled by CCNYc as well as PFTK1 and TPM4. As a result, CCNY was mainly expressed in lung cancer. CCNYc could promote cell motility and invasion. It indicated that CCNYc/PFTK1 complex could promote cell metastasis by regulating the formation of F-actin via TPM4.

As label-free biomarkers, electrical properties of single cells have been widely used for cell-type classification and cell-status evaluation. However, as intrinsic bioelectrical markers, previously reported membrane capacitance and cytoplasmic resistance (e.g., specific membrane capacitance Cspecific membrane and cytoplasmic conductivity σcytoplasm ) of tumor subtypes were derived from tens of single cells, lacking statistical significance due to low cell numbers. In this study, tumor subtypes were constructed based on phenotype (treatment with 4-methylumbelliferone) or genotype (knockdown of ROCK1) modifications and then aspirated through a constriction-channel based impedance flow cytometry to characterize single-cell Cspecific membrane and σcytoplasm . Thousands of single tumor cells with phenotype modifications were measured, resulting in significant differences in 1.64 ± 0.43 μF/cm2 vs. 1.55 ± 0.47 μF/cm2 of Cspecific membrane and 0.96 ± 0.37 S/m vs. 1.24 ± 0.47 S/m of σcytoplasm for 95C cells (792 cells of 95C-control vs. 1529 cells of 95C-pheno-mod); 2.56 ± 0.88 μF/cm2 vs. 2.33 ± 0.56 μF/cm2 of Cspecific membrane and 0.83 ± 0.18 S/m vs. 0.93 ± 0.25 S/m of σcytoplasm for H1299 cells (962 cells of H1299-control vs. 637 cells of H1299-pheno-mod). Furthermore, thousands of single tumor cells with genotype modifications were measured, resulting in significant differences in 3.82 ± 0.92 vs. 3.18 ± 0.47 μF/cm2 of Cspecific membrane and 0.47 ± 0.05 vs. 0.52 ± 0.05 S/m of σcytoplasm (1100 cells of A549-control vs. 1100 cells of A549-geno-mod). These results indicate that as intrinsic bioelectrical markers, specific membrane capacitance and cytoplasmic conductivity can be used to classify tumor subtypes.

Mesoporous melamine-silver (MA-Ag) nanocomposites doped with carbon nitride quantum dots (CNQDs) were fabricated simply by the controlled supramolecular self-assembly. It was discovered that the resulting nanoflower-like CNQDs@MA-Ag nanocomposites could exhibit the peroxidase-like catalysis, which could be specifically enhanced by Hg2+ by forming Ag@Hg alloys. A double catalysis-based colorimetric method was thereby developed for the fast detecting of Hg2+ and Hg0 in wastewater samples, with the levels down to 0.050 nM and 18.3 nM, respectively. Moreover, strong visible-light-driven photocatalysis of the nanocomposites was demonstrated for oxidizing Hg0 into Hg2+ through photocatalytic H2O2 production so as to realize the detoxification of Hg0 in the environmental wastewater. Besides, the fabricated mesoporous CNQDs@MA-Ag nanocomposites with large specific surface areas might facilitate the high Hg adsorption through the powerful MA-Hg chelate interaction, showing the efficient adsorption and/or removal of total Hg. The catalysis-selective colorimetric analysis and photocatalysis-based detoxification removal of total mercury may promise for wide applications in the environmental monitoring and wastewater treatment of toxic heavy metals of mercury.

Mussel-inspired enhancement of Fe3O4 catalysis was discovered towards a highly selective and sensitive colorimetric strategy for the magnetic separation-based evaluation of dopamine and/or levodopa in urine, in which the specific interaction of bis-catechol-containing analytes and mesoporous Fe3O4 NPs would form highly stable complexes of bis-catechol-Fe coordination.

Background. Keratin 23 (KRT23) is a new member of the KRT gene family and known to be involved in the development and migration of various types of tumors. However, the role of KRT23 in ovarian cancer (OC) remains unclear. This study is aimed at investigating the function of KRT23 in OC. Methods. The expression of KRT23 in normal ovarian and OC tissues was determined using the Oncomine database and immunohistochemical staining. Reverse transcription quantitative polymerase chain reaction assay was used to analyze the expression of KRT23 in normal ovarian epithelial cell lines and OC cell lines. Small interfering RNA (siRNA), wound healing assay, and transwell assay were conducted to detect the effects of KRT23 on OC cell migration and invasion. Further mechanistic studies were verified by the Gene Expression Profiling Interactive Analysis platform, Western blotting, and immunofluorescence staining. Results. KRT23 was highly expressed in OC tissues and cell lines. High KRT23 expression could regulate OC cell migration and invasion, and the reduction of KRT23 by siRNA inhibited the migration and invasion of OC cells in vitro. Furthermore, KRT23 mediated epithelial-mesenchymal transition (EMT) by regulating p-Smad2/3 levels in the TGF-β/Smad signaling pathway. Conclusions. These results demonstrate that KRT23 plays an important role in OC migration via EMT by regulating the TGF-β/Smad signaling pathway.

An efficient photocatalyst of nitrogen (N)-doped Cu2O@CuO was constructed for H2O2 production under visible light simply by the one-step N2 plasma treatment for Cu2O octahedrons. It was discovered that the plasma treatment could allow for the simultaneous N doping and Cu2O oxidation to yield the N-doped Cu2O@CuO heterostructure so as to boost the separation and transferring of photogenerated carriers of photocatalysis. More interestingly, the photocatalytic performances of the N-doped Cu2O@CuO could controllably depend on the plasma treatment time, with the highest H2O2 production rate (about 14 μMg−1min−1) at the 10-min plasma treatment, which is over three and eight folds higher than that of Cu2O and CuO, respectively. Also, high photochemical stability of the photocatalyst could be expected for photocatalytic cycles. A two-step single electron transfer pathway was demonstrated for the photocatalytic oxygen reduction reactions of H2O2 evolution through the formation of dominated O2− radicals. This one-step plasma treatment route may provide a facile and efficient construction of photocatalytic heterostructures, promising for the large-scale applications for designing various efficient photocatalysts for H2O2 productions under visible light.

In recent years, a variety of composite materials preparation technology has been updated, from ceramic matrixcomposites, metal matrix composites to polymer matrix composites, a variety of preparation techniques have beengreatly improved, making the composite properties and applications signifi cantly improved. This paper reviews severalimportant preparation methods and applications of ceramic matrix composites, metal matrix composites and polymermatrix composites.

AZD9291 is an irreversible, small-molecule inhibitor which has potency against mutant EGFR- and T790M-resistant mutation. Despite the encouraging efficacy in clinical, the acquired resistance will finally occur. Further study will need to be done to identify the acquired resistance mechanisms and determine the next treatment. We established an AZD9291-resistant cell line (HCC827/AZDR) from parental HCC827 cell line through stepwise pulsed selection of AZD9291. The expression of EGFR and its downstream pathways were determined by western blot analysis or immunofluorescence assay. The sensitivity to indicated agents were evaluated by MTS. Compared with parental HCC827 cells, the HCC827/AZDR cells showed high resistance to AZD9291 and other EGFR-TKIs, and exhibited a mesenchymal-like phenotype. Almost complete loss of EGFR expression was observed in HCC827/AZDR cells. But the activation of downstream pathway, MAPK signaling, was found in HCC827/AZDR cells even in the presence of AZD9291. Inhibition of MAPK signaling had no effect on cell viability of HCC827/AZDR and could not reverse AZD9291 resistance because of the subsequent activation of AKT signaling. When treated with the combination of AKT and MAPK inhibitor, HCC827/AZDR showed remarkable growth inhibition. Loss of EGFR could be proposed as a potential acquired resistance mechanism of AZD9291 in EGFR-mutant NSCLC cells with an EMT phenotype. Despite the loss of EGFR, the activation of MAPK pathway which had crosstalk with AKT pathway could maintain the proliferation and survival of resistant cells. Blocking MAPK and AKT signaling may be a potential therapeutic strategy following AZD9291 resistance.

Triptolide is a diterpenoid compound that inhibits the inflammation of rheumatoid arthritis (RA). However, the use of triptolide is limited due to its strong gastrointestinal toxicity. The purpose of this work was to develop a transdermal delivery system for triptolide to reduce this toxicity. A microemulsion-based hydrogel (MBH) was prepared from the combination of Gemseal 40-oleic acid as oil phase, Tween 80-labrasol as surfactant, anhydrous ethanol as co-surfactant, water as aqueous phase and Poloxamer 407 as hydrogel matrix. Rheological measurements, environmental scanning electron microscopy (ESEM) and transdermal experiments in vitro were used to characterize triptolide-loaded and blank MBH preparations. The effects of Poloxamer 407 and triptolide on the rheological properties and microstructures of the MBH were determined. Transparent and homogeneous MBH could only be formed when the concentration of Poloxamer 407 in the selected O/W microemulsion was in the range of 14.0–16.0% ( w / w ). When the concentration of Poloxamer 407 increased, the rheological properties such as the yield stresses ( σ y ), storage and loss moduli ( G ′, G ″) of the formulations increased, and the network structures became more compact. The addition of triptolide did not change the interconnected network structures of the MBH preparations. MBH preparations afford a better sustained release profile when compared to microemulsions, a finding confirmed by an in vitro permeation test in mice. MBH appears to be a promising vehicle for transdermal delivery of triptolide.

This paper presents a 96-well microfabricated assay to study three-dimensional (3D) invasion of tumor cells. A 3D cluster of tumor cells was first generated within each well by seeding cells onto a micro-patterned surface consisting of a central fibronectin-coated area that promotes cellular attachment, surrounded by a poly ethylene glycol (PEG) coated area that is resistant to cellular attachment. Following the formation of the 3D cell clusters, a 3D collagen extracellular matrix was formed in each well by thermal-triggered gelation. Invasion of the tumor cells into the extracellular matrix was subsequently initiated and monitored. Two modes of cellular infiltration were observed: A549 cells invaded into the extracellular matrix following the surfaces previously coated with PEG molecules in a pseudo-2D manner, while H1299 cells invaded into the extracellular matrix in a truly 3D manner including multiple directions. Based on the processing of 2D microscopic images, a key parameter, namely, equivalent invasion distance (the area of invaded cells divided by the circumference of the initial cell cluster) was obtained to quantify migration capabilities of these two cell types. These results validate the feasibility of the proposed platform, which may function as a high-throughput 3D cellular invasion assay.

A series of ZnO and graphene composites (ZnO/GRs) was synthesized by a simple and nontoxic hydrothermal reaction route. The TEM, AFM, FTIR, Raman and current–voltage (I–V) results demonstrated that the ZnO particles were coated by the graphene sheets, confirming the formation of ZnO/GRs composites. During the photocatalytic test, in comparison with ZnO and P25, the ZnO/GRs exhibited enhanced photocatalytic performance for degradation of methylene blue (MB) dye since the graphene sheets could prevent the photoinduced hole–electron pairs of ZnO from recombination by transferring the photoinduced electron to the MB. When the mass ratio of ZnO to graphene was 50:1, the ZnO/GR showed the best photocatalytic performance. Moreover the photocorrosion of ZnO was inhibited to a large extent, which could be attributed to the formation of ZnO and graphene composite.

Large-scale arrayed ZnO nanocrystals with two different expose surfaces, including ZnO hexagonal nanoplatforms with the major expose plane of (0 0 0 1) and hamburger-like samples with the nonpolar planes of { 1 0 1 ¯ 0 } mainly exposed, were successfully fabricated by a simple hydrothermal method. Mechanisms for compare the photocatalytic activity of two typical ZnO nanostructures were systematic explained as the key point in the paper. Compared with the hamburger-like ZnO nanostructures, the ZnO with hexagonal platform-like morphology exhibited improved ability on the photocatalytic degradation of Rhodamine B (RhB) in aqueous solution under UV radiation. The relative higher photocatalytic activity of the ZnO hexagonal nanoplatforms was attributed to the exposed polar surfaces and the content of oxygen vacancy on the nanostructures surface. The Zn-terminated (0 0 0 1) polar face and the surface defects are facile to adsorb O 2− and OH − ions, resulting in a greater production rate of O 2 − and OH − , hence promoting the photocatalysis reaction.

A new 3D lanthanide metal–organic framework, {[Ce(L)(DMF)]·2.5(DMF)·3(H2O)}n (1) (H3L = N,N′,N″-tris(4-carboxyphenyl)-1,3,5-benzenetricarboxamide, DMF = N,N′-dimethylformamide) has been synthesized under solvothermal condition. Compound 1 features a 3D non-interpenetrated binodal (4, 8)-connected AlB2 topology with a Schlafli symbol of (45.6)2(410.614.84), where the C3 symmetry ligand H3L evolves into an unusual 4-connected node and dinuclear cerium cluster acts as an 8-connected node. Furthermore, compound 1 displays blue emission in the solid state at room temperature.

Purpose Silent information regulator protein 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase that is abundantly expressed in vascular endothelial cells (VECs), and it has an essential role in angiogenesis. However, its contribution to retinal vascular development remains unclear. Here we characterize its involvement in regulating this process under both physiological and pathologic conditions. Methods Endothelium-specific Sirt1 knockout mice were established using the Cre-lox system. VECs were isolated using magnetic beads and identified by immunostaining. Retinal whole-mount staining analyzed the retinal vascular patterns. SIRT1 was knocked down or overexpressed in human retinal microvascular endothelial cells (HRMECs) using small interfering RNA (siRNA) or lentivirus infection, respectively. Scratch assay, Transwell, and Matrigel angiogenesis assay evaluated cell migration and tube formation, respectively. Quantitative RT-PCR analyzed genes regulating VEC migration. Western blotting determined protein expression. Coimmunoprecipitation detected the interaction of hypoxia-inducible factor 1α (HIF-1α) and SIRT1 as well as acetylation status of HIF-1α. Results Specific deletion of Sirt1 in VECs dramatically delayed retinal vessel expansion and reduced vessel density. In the oxygen-induced retinopathy (OIR) mouse model, Sirt1 ablation markedly suppressed retinal revascularization and consequently increased retinal avascularity. SIRT1 downregulation in HRMECs inhibited cell migration and tube formation, while overexpression of SIRT1 had the opposite effects. Vascular endothelial growth factor-A (VEGF-A)/VEGF receptor-2 (VEGFR-2), and matrix metalloproteinases 14 (MMP14) expression significantly declined in Sirt1-null VECs, as well as SIRT1 siRNA-transfected HRMECs. SIRT1 downregulation upregulated the HIF-1α acetylation status. Conversely, SIRT1 overexpression decreased this response. Conclusions SIRT1 contributes to both physiological and pathologic retinal angiogenesis through promoting retinal VEC migration. Its underlying molecular mechanism involves SIRT1-mediated deacetylation of HIF-1α and subsequent upregulation of VEGF-A/VEGFR-2 and MMP14 expression.

As increases in hepatocyte growth factor/scatter factor (HGF/SF) induce retinal pigment epithelial (RPE) migration and proliferation into the vitreous cavity and contribute to proliferative vitreoretinopathy (PVR) development, we determined if changes in miR-182 expression affect such behavioral changes. We found that miR-182 expression was less in PVR clinical samples than in primary RPE cells whereas c-Met was upregulated. Ectopic miR-182 inhibited RPE cell proliferation, cell cycle, and migration. Bioinformatic analysis identified c-Met as a miR-182 target, which was confirmed with the luciferase reporter assay. Transfection of miR-182 into RPE cells induced c-Met downregulation, which led to reduced cell proliferation and migration through declines in p-Akt formation. MiR-182 downregulation along with c-Met upregulation in PVR tissues suggest that these two opposing effects play important roles in PVR development. As ectopic miR-182 expression suppressed RPE cell proliferation and migration, strategies to selectively upregulate miR-182 expression in a clinical setting may provide a novel option to treat this disease.