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The aim of this study was to evaluate the value of metagenomic next-generation sequencing (mNGS) in peripheral pulmonary infection management by comparing the diagnostic yield of mNGS and traditional pathogen detection methods on interventional specimens obtained by bronchoscopy. Patients and Methods: This study enrolled patients suspected with pulmonary infection who were admitted to Tianjin Medical University General Hospital from June 2018 to August 2019. Specimens were obtained from bronchoscopy for mNGS analysis and traditional pathogen detection (including bronchoalveolar lavage fluid microbial culture, smear microscopy, and lung biopsy histopathology), and the diagnostic yields were compared between mNGS and traditional methods to evaluate the diagnostic value of mNGS in peripheral pulmonary infection diagnosis. Results: In this study, by comparing mNGS with traditional pathogen detection, the results indicated that, first, mNGS identified at least one microbial species in almost 89% of the patients with pulmonary infection; second, mNGS detected microbes related to human diseases in 94.49% of samples from pulmonary infection patients who had received negative results from traditional pathogen detection; third, the accuracy and sensitivity of mNGS are higher than those of traditional pathogen detection; and, finally, mNGS could simultaneously detect and identify a large variety of pathogens. Conclusion: Metagenomic NGS analysis provided fast and precise pathogen detection and identification, contributing to prompt and accurate treatment of peripheral pulmonary infection.

Exploring the synthesis and biomedical applications of biocompatible quantum dots (QDs) is currently one of the fastest growing fields of nanotechnology. Hence, in this work, we present a facile approach to produce water-soluble (cadmium-free) quaternary Zn-Ag-In-S (ZAIS) QDs. Their efficient photoluminescence (PL) emissions can be tuned widely in the range of 525-625 nm by controlling the size and composition of the QDs with the PL quantum yields (QYs) of 15-30%. These highly luminescent ZAIS QDs are less toxic due to the absence of highly toxic cadmium, and can be versatilely modified by a DHLA-PEG-based ligand. Importantly, after being modified by tumor cell-specific targeting ligands (e.g., folate and RGD peptide), the PEGylated quaternary QDs show potential applications in tumor cell imaging as a promising alternative for Cd-based QDs.

Background Emerging studies showed curcumin can inhibit glioblastoma and breast cancer cells via regulating ferroptosis. However, the role of ferroptosis in the inhibitory effect of curcumin on non‐small‐cell lung cancer (NSCLC) remains unclear. Methods Cell counting kit‐8 (CCK‐8) assay was used to measure the viability of A549 and H1299 cells under different conditions. Cell proliferation was examined by Ki67 immunofluorescence. The morphological changes of cells and tumor tissues were observed by optical microscope and hematoxylin and eosin (H&E) staining. Intracellular reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and iron contents were determined by corresponding assay kit. The related protein expression levels were detected by western blot and immunohistochemistry. Transmission electron microscope was used to observe ultrastructure changes of A549 and H1299 cells. Results Curcumin inhibited tumor growth and cell proliferation, but promoted cell death. Characteristic changes of ferroptosis were observed in curcumin group, including iron overload, GSH depletion and lipid peroxidation. Meanwhile, the protein level of ACSL4 was higher and the levels of SLC7A11 and GPX4 were lower in curcumin group than that in control group. Incubation of ferroptosis inhibitors ferrostatin‐1 (Fer‐1) or knockdown of iron‐responsive element‐binding protein 2 (IREB2) notably weakened curcumin‐induced anti‐tumor effect and ferroptosis in A549 and H1299 cells. Further investigation suggested that curcumin induced mitochondrial membrane rupture and mitochondrial cristae decrease, increased autolysosome, increased the level of Beclin1 and LC3, and decreased the level of P62. Curcumin‐induced autophagy and subsequent ferroptosis were both alleviated with autophagy inhibitor chloroquine (CQ) or siBeclin1. Conclusion Curcumin induced ferroptosis via activating autophagy in NSCLC, which enhanced the therapeutic effect of NSCLC.

Adriamycin (ADM) has been effective against many types of solid tumors in clinical applications. However, its use is limited because of systemic toxicities, primarily cardiotoxicity, and multidrug resistance. In this study, a new active receptor-mediated complex, ADM conjugated with 2-amino-2-deoxy-D-glucose and succinic acid (2DG-SUC-ADM), was designed to target tumor cells through glucose transporter 1 (GLUT1). MTT assay and confocal images showed that the complex had better inhibition rate to tumor cells and low toxicity to normal cells. Most importantly, the complex displayed a potential to reverse overcome multidrug resistance in cancer cells, with more complex transported into the nucleus of tumor cells. Our in vivo experiments also showed that this new complex could significantly decrease organ toxicity and enhance the antitumor efficacy compared with free ADM, indicating a promising drug of 2DG-SUC-ADM for targeted cancer therapy. Cancer Res; 73(4); 1362-73. Ó2012 AACR.