c-Rel is a Novel Oncogene in Lung Squamous Cell Carcinoma Regulating Cell Proliferation and Migration.

Lung squamous cell carcinoma (LUSC) accounts for approximately 25% to 30% of lung cancers, but largely no targeted therapy is available against it, calling for identification of new oncogenes in LUSC growth for new therapeutic targets. In this study, REL was identified through a screening for oncogenes that are highly amplified in human LUSC. Its expression was associated with poor prognosis in LUSC patients. Furthermore, knockdown of c-Rel in LUSC cell lines lead to significant decrease in cell proliferation and migration. Mechanistically, c-Rel knockdown suppressed NFκB pathway by blocking phosphorylation of IκB. Consistently, pharmaceutic inhibition of c-Rel also. In orthotopic xenograft lung cancer mouse model, c-Rel knockdown inhibited the tumor growth. Cancer cell proliferation and epithelial-mesenchymal-transition (EMT) of the tumors were impaired by c-Rel knockdown. Finally, it's confirmed in precision-cut tumor slices of LUSC that deletion of c-Rel inhibits the NFκB pathway and cancer cell growth. Accordingly, we hypothesize that c-Rel promotes the activation of the NFκB pathway by promoting the phosphorylation of IκB in LUSC. Our study reveals REL as a novel LUSC oncogene and provides new insights into the molecular regulation of LUSC, which will provide new therapeutic targets for the treatment of squamous lung cancer.

Interaction of Cerium Oxide Nanoparticles and Ionic Cerium with Duckweed (Lemna minor L.): Uptake, Distribution, and Phytotoxicity.

As one of the most widely used nanomaterials, CeO2 nanoparticles (NPs) might be released into the aquatic environment. In this paper, the interaction of CeO2 NPs and Ce3+ ions (0~10 mg/L) with duckweed (Lemna minor L.) was investigated. CeO2 NPs significantly inhibited the root elongation of duckweed at concentrations higher than 0.1 mg/L, while the inhibition threshold of Ce3+ ions was 0.02 mg/L. At high doses, both reduced photosynthetic pigment contents led to cell death and induced stomatal deformation, but the toxicity of Ce3+ ions was greater than that of CeO2 NPs at the same concentration. According to the in situ distribution of Ce in plant tissues by µ-XRF, the intensity of Ce signal was in the order of root > old frond > new frond, suggesting that roots play a major role in the uptake of Ce. The result of XANES showed that 27.6% of Ce(IV) was reduced to Ce(III) in duckweed treated with CeO2 NPs. We speculated that the toxicity of CeO2 NPs to duckweed was mainly due to its high sensitivity to the released Ce3+ ions. To our knowledge, this is the first study on the toxicity of CeO2 NPs to an aquatic higher plant.

Particulate Standard Establishment for Absolute Quantification of Nanoparticles by LA-ICP-MS.

The development of nanotechnology has transformed many cutting-edge studies related to single-molecule analysis into nanoparticle (NP) detection with a single-NP sensitivity and ultrahigh resolution. While laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been successful in quantifying and tracking NPs, its quantitative calibration remains a major challenge due to the lack of suitable standards and the uncertain matrix effects. Herein, we frame a new approach to prepare quantitative standards via precise synthesis of NPs, nanoscale characterization, on-demand NP distribution, and deep learning-assisted NP counting. Gold NP standards were prepared to cover the mass range from sub-femtogram to picogram levels with sufficient accuracy and precision, thus establishing an unambiguous relationship between the sampled NP number in each ablation and the corresponding mass spectral signal. Our strategy facilitated for the first time the study of the factors affecting particulate sample capture and signal transductions in LA-ICP-MS analysis and culminated in the development of an LA-ICP-MS-based method for absolute NP quantification with single-NP sensitivity and single-cell quantification capability. The achievements would herald the emergence of new frontiers cut across a spectrum of toxicological and diagnostic issues related to NP quantification.

Immobilized short-chain dehydrogenase/reductase on Fe3O4 particles acts as a magnetically recoverable biocatalyst component in patulin bio-detoxification system.

Patulin is one of the most important mycotoxins that contaminates fruit-derived products and causes acute or chronic toxicity in humans. In the present study, a novel patulin-degrading enzyme preparation was developed by taking a short-chain dehydrogenase/reductase and covalently linking it to dopamine/polyethyleneimine co-deposited magnetic Fe3O4 particles. Optimum immobilization provided 63% immobilization efficiency and 62% activity recovery. Moreover, the immobilization protocol substantially improved thermal and storage stabilities, proteolysis resistance, and reusability. Using reduced nicotinamide adenine dinucleotide phosphate as a cofactor, the immobilized enzyme exhibited a detoxification rate of 100% in phosphate-buffered saline and a detoxification rate of more than 80% in apple juice. The immobilized enzyme did not cause adverse effects on juice quality and could be magnetically separated quickly after detoxification to ensure convenient recycling. Moreover, it did not exhibit cytotoxicity against a human gastric mucosal epithelial cell line at a concentration of 100 mg/L. Consequently, the immobilized enzyme as a biocatalyst had the characteristics of high efficiency, stability, safety, and easy separation, establishing the first step in building a bio-detoxification system to control patulin contamination in juice and beverage products.

Impact of Albumin Pre-Coating on Gold Nanoparticles Uptake at Single-Cell Level.

Nanoparticles (NPs) suspension is thermodynamically unstable, agglomeration and sedimentation may occur after introducing NPs into a physiological solution, which in turn affects their recognition and uptake by cells. In this work, rod-like gold NPs (AuNRs) with uniform morphology and size were synthesized to study the impact of bovine serum albumin (BSA) pre-coating on the cellular uptake of AuNRs. A comparison study using horizontal and vertical cell culture configurations was performed to reveal the effect of NPs sedimentation on AuNRs uptake at the single-cell level. Our results demonstrate that the well-dispersed AuNRs-BSA complexes were more stable in culture medium than the pristine AuNRs, and therefore were less taken up by cells. The settled AuNRs agglomerates, although only a small fraction of the total AuNRs, weighed heavily in determining the average AuNRs uptake at the population level. These findings highlight the necessity of applying single-cell quantification analysis in the study of the mechanisms underlying the cellular uptake of NPs.

Nanoparticles Determination by Laser Ablation Inductively Coupled Plasma Mass Spectrometry.

Quantitatively studying the biodistribution and transformation of nanomaterials is of great importance for nanotoxicological evaluation. Recently, laser ablation inductively coupled plasma mass spectrometry has been employed to distinguish nanoparticles (NPs) with their dissolved ions in biological samples. The principle of the proposal is based on a hypothesis that the intact NPs sampled by laser ablation will generate discrete sharp pulses of signals in ICP-MS measurement, being totally different from the continuous, relatively lower signals generated by ions. However, it is still a controversy whether NPs could maintain their intactness during the laser ablation. This work found a way to exactly determine the number of NPs sampled for each LA-ICP-MS measurement. It made possible to reveal the signal profile of a single NP in LA-ICP-MS analysis. The results suggest that AuNR, AgNP and TIO2 NP were broken into much smaller secondary NPs during the laser ablation, therefore generating continuous signals in the analyzer. There was a certain probability that the fragmentation of large-sized NP or multiple NPs by laser ablation was not sufficient, leaving some NPs unbroken or some secondary NPs with relatively large sizes to generate discrete pulses of signals in the analyzer. When the intactness of NPs during laser ablation cannot be assured, it is impossible to determine the attribution of mass spectrum signals. These findings compromise the reliability of distinguishing NPs from their dissolved ions by LA-ICP-MS.

Radiolabeling of Nanomaterials: Advantages and Challenges.

Quantifying the distribution of nanomaterials in complex samples is of great significance to the toxicological research of nanomaterials as well as their clinical applications. Radiotracer technology is a powerful tool for biological and environmental tracing of nanomaterials because it has the advantages of high sensitivity and high reliability, and can be matched with some spatially resolved technologies for non-invasive, real-time detection. However, the radiolabeling operation of nanomaterials is relatively complicated, and fundamental studies on how to optimize the experimental procedures for the best radiolabeling of nanomaterials are still needed. This minireview looks back into the methods of radiolabeling of nanomaterials in previous work, and highlights the superiority of the "last-step" labeling strategy. At the same time, the problems existing in the stability test of radiolabeling and the suggestions for further improvement are also addressed.

Effects of surface modification on toxicity of CeO2 nanoparticles to lettuce.

Phytotoxicity of nanoceria (nCeO2) has been reported, but there are few studies on how to reduce its phytotoxicity. In the present study, we modified nCeO2 with two organophosphates (nCeO2@ATMP and nCeO2@EDTMP) and compared their toxicity to lettuce with that of uncoated nCeO2. The results showed that bare nCeO2 significantly inhibited the root growth of lettuce, leading to oxidative damages and root cell death. In contrast, after surface modification, the toxicity of nCeO2@ATMP to lettuce was weakened, while nCeO2@EDTMP was nontoxic to lettuce. It was found that the surface properties of the modified materials have been changed, resulting in sharp decreases in their bioavailability. Although nCeO2 with and without surface coatings were all transformed when interacting with plants, the absolute contents of Ce(III) in roots treated with modified nCeO2 decreased significantly, which may be the main reason for the reduction of toxicity. This study indicates that it is feasible to reduce the phytotoxicity of nanomaterials through surface coating.

Detection of tuberculosis laboratory cross-contamination using whole-genome sequencing.

OBJECTIVE: Detection of tuberculosis laboratory cross-contamination using whole-genome sequencing. METHODS: A total of 22 M. tuberculosis strains with high genotypic homology from one hospital were collected during the drug resistance surveillance. Genome sequencing and epidemiological investigation were conducted to determine the occurrence of cross-contamination. RESULTS: The pair wise comparison between the genomes in each cluster indicated that 15 (71.4%) of 21 strains with available genomic data had no SNP differences with at least one other strain within the same cluster. The analysis of the specimen collection time found that, among the 16 strains collected on the same day, 14 (87.5%) of them had no SNP differences with one another strain; meanwhile, among the strains within the same cluster whose SNP distance was 0, 93.3% (14/15) of them had the same collection time, suggesting that these findings were most likely caused by cross contamination. CONCLUSION: A high proportion of M. tuberculosis strains with genotypic homology from the single institute that shared the same process time period was most likely caused by the cross contamination. Whole genome sequencing analysis can help to determine the occurrence of cross contamination.