Ferroptosis is anew form of regulated cell death that shows promise for tumor treatment. Most current ferroptosis tumor therapies are based on the intrinsic pathological features of the malignancies,and it would be of clinical significance to develop ferroptosis-inducing strategies with improved tumor specificity and modulability.Here we report ap olydopaminebased nanoplatform (Fe II PDA@LAP-PEG-cRGD) for the efficient loading of Fe 2+ and b-lapachone (LAP), which could readily initiate ferroptosis in tumor cells upon treatment with near-infrared light. PDAn anostructures could generate mild hyperthermia under NIR irritation and trigger the release of the ferroptosis-inducing Fe 2+ ions.T he NIR-actuated photothermal effect would also activate cellular heat shock response and upregulate the downstream NQO1 via HSP70/NQO1 axis to facilitate bioreduction of the concurrently released b-lapachone and enhance intracellular H 2 O 2 formation to promote the Fe 2+ -mediated lipid peroxidation.

Breast cancer is a major public health concern, due to its increasing incidence and limited effective treatment. The present study aimed to investigate the expression of microRNA (miR)-194-5p and its roles in breast cancer. The expression levels of miR-194-5p and SRY-box 17 (SOX17) mRNA were detected in breast cancer tissues and cell lines by reverse transcription-quantitative polymerase chain reaction. The protein expression levels were determined by western blotting. In addition, MTT, colony formation, scratch and Transwell assays were use to evaluate the characteristics of MCF-7 cells with miR-194-5p knockdown. The target verification of miR-194-5p was determined by luciferase reporter assay. Furthermore, tumor-bearing nude mice with miR-194-5p knockdown were used to assess the effects of miR-194-5p on tumor activity. In breast cancer tissues, miR-194-5p was upregulated, whereas SOX17 was downregulated. In addition, the expression levels of SOX17 and phosphorylated (p)-β-catenin in the cytosol and nucleus were increased in the miR-194-5p inhibitor group. In addition, cell proliferation, migration and invasion were inhibited in response to miR-194-5p knockdown. The luciferase reporter assay confirmed that SOX17 was a target gene of miR-194-5p. In the mouse studies, knockdown of miR-194-5p suppressed tumor growth and promoted SOX17 expression in nude mice with breast cancer. These findings suggested that knockdown of miR-194-5p may increase the expression of SOX17 and regulate the Wnt/β-catenin signaling pathway in breast cancer cells; therefore, miR-194-5p may be considered a potential target for breast cancer prevention.

Accurate detection and imaging of tumor-related microRNA (miRNA) in living cells hold great promise for early cancer diagnosis and prognosis. One of the challenges is to develop methods that enable the identification of multiple miRNAs simultaneously to further improve the detection accuracy. Herein, a simultaneous detection and imaging method of two miRNAs was established by using a programmable designed DNA tetrahedron nanostructure (DTN) probe that includes a nucleolin aptamer (AS1411), two miRNA capture strands, and two pairs of metastable catalytic hairpins at different vertexes. The DTN probe exhibited enhanced tumor cell recognition ability, excellent stability and biocompatibility, and fast miRNA recognition and reaction kinetics. It was found that the DTN probe could specifically enter tumor cells, in which the capture strand could hybridize with miRNAs and initiate the catalytic hairpin assembly (CHA) only when the overexpressed miR-21 and miR-155 existed simultaneously, resulting in a distinct fluorescence resonance energy transfer signal and demonstrating the feasibility of this method for tumor diagnosis.

No abstract

Plant community structure responds strongly to anthropogenic disturbances, which greatly influence community stability. The changes in community structure, aboveground biomass (AGB), biodiversity and community stability associated with different management practices were studied with a three-year field investigation in a temperate steppe of Inner Mongolia, China. The species richness, Shannon-Wiener index, evenness, plant functional type abundance, AGB, temporal community stability, summed covariance, scaling coefficient and dominant species stability were compared among areas subjected to long-term reservation (R), long-term grazing (G), mowing since enclosure in 2008 (M) and grazing enclosure since 2008 (E). Site R had higher perennial grass abundance and lower species richness than sites G, M and E, although the AGB was not significantly different among the four sites. The species structure varied from a single dominant species at site R to multiple dominant species at sites G, M and E. The long-term reservation grassland had lower biodiversity but higher stability, whereas the enclosed grassland with/without mowing had higher biodiversity but lower stability. Different stability mechanisms, such as the compensatory dynamics, mean-variance scaling and dominant species stability were examined. Results showed that community stability was most closely related to the relative stability of the dominant species, which supports the biomass ratio hypothesis proposed by Grime.