Abstract Background The features of resistance to mitophagy contribute significantly to invasion, malignancy and cell survival. But the mechanism of mitophagy in clear cell renal cell carcinoma (ccRCC) remains unclear It is valuable to estimate mitophagy molecular characters as a clinical factor for prognosis and immune phenotypes in ccRCC. Methods Clinical data of ccRCC patients, including genome and transcriptome data, were downloaded from The Cancer Gene Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database. The differentially expressed genes (DEGs) of patient clusters determined by mitophagy gene expression and univariate Cox regression analysis were identified and used to classify patient clusters for constructing mitophagy scores via PCA analysis. Immune cell infiltration and immune cell function were analyzed by ssGSEA algorithm and TIDE algorithm. Results Based on the expression of mitophagy marker genes, ccRCC patients were divided into three mitophagy clusters with different gene expression patterns, prognosis and immune niches. 1,356 DEGs of mitophagy clusters related with prognosis were screened out for building mitophagy score. ccRCC patients with high mitophagy scores have better prognosis. Meanwhile, lower mitophagy patients with high expressed several immune-checkpoint proteins and had high immunophenoscore after immune-checkpoint blockers treatment, indicating better responsiveness to immune therapy. Conclusions mitophagy features are tightly correlated with ccRCC prognosis and immune responsiveness. mitophagy score built here is able to predict the prognosis and immune features of ccRCC patients and be indicative for immunotherapy.
Environmental natural organic matters (NOMs) have great effects on the physicochemical properties of engineering nanoparticles, which may impact the transport of nanoparticles across plasma membrane and the cytotoxicity. Therefore, the kinetics, uptake pathway and mass of transporting into A549 cell membrane of silver nanoparticles (AgNPs) coated with citric acid (CA), tartaric acid (TA) and fulvic acid (FA) were investigated, respectively. CA, FA and TA enhanced the colloidal stability of AgNPs in culture medium and have greatly changed the surface plasmon resonance spectrum of AgNPs due to the absorption of CA, FA and TA on surface of AgNPs. Internalizing model showed that velocity of CA-, TA- and FA-nAg transporting into A549 cell were 5.82-, 1.69- and 0.29-fold higher than those of the control group, respectively. Intracellular mass of Ag was dependent on mass of AgNPs delivered to cell from suspension, which obeyed Logistic model and was affected by NOMs that CA- and TA-nAg showed a large promotion on intracellular mass of Ag. The lipid raft/caveolae-mediated endocytosis (LME) of A549 cell uptake of AgNPs were susceptible to CA, TA and FA that uptake of CA-, TA- and FA-nAg showed lower degree of dependent on LME than that of the control (uncoated AgNPs). Actin-involved uptake pathway and macropinocytosis would have less contribution to uptake of FA-nAg. Overall, transmembrane transport of NOMs-coated AgNPs differs greatly from that of the pristine AgNPs.
Abstract The properties of modified polypropylene (PP) materials are closely related to their phase structure. In this work, polyolefin elastomer (POE)‐toughened PP materials with different phase structures were designed by using various types of POEs (ethylene‐butene 710, 110, ethylene‐propylene 6202, ethylene‐octene 8200). Then, the effects of phase separation in PP/POE blends on both thermal and tensile properties as well as ultraviolet (UV) resistance were investigated. The results revealed that the POE type hardly affected the melt flow rate, melting or crystallization behavior of the modified PP samples. Moreover, scanning electron microscopy results showed that POE6202 had a smaller dispersed phase size in PP (0.1–0.5 μm), which improved the low‐temperature elongation at break. PP/POE110 blends with a larger microdomain (1–5 μm) had better high‐temperature tensile strength. Further, when toughened with POE110 and POE6202 simultaneously, modified PP had excellent low‐temperature elongation (272%@ −40°C) without sacrificing as much of its high‐temperature tensile strength (10.4 MPa@70°C). Finally, Electron Paramagnetic Resonance tests showed that the addition of amorphous POE decreased the intensity of free radicals generated in PP during irradiation and promoted their attenuation during decay. This indicated that the introduction of POE improved the UV resistance of PP.
Hypoxia, a lack of oxygen at a non-physiological level, increases heme oxygenase-1 (HO-1) expression. Endogenous carbon monoxide (CO) is mainly derived from degraded heme owing to HO-1 expression, which acts as a pivotal part in vasodilation and neurotransmitter, anti-inflammatory and anti-apoptosis process. Due to the significant role of CO in vivo, the real-time monitoring of endogenous CO is of particularly importance. However, when detecting the CO in vivo, the catalysis of heavy metal ions usually required in previous reports, which would restrict the bio-applications of the CO probe. To overcome this difficulty, herein, a turn-on silicone fluorescence probe (SAH-N) has been reasonably designed, which does not require the catalytic effect of metal ions in CO reduction process. SAH-N shows superior concentration dependence property in hypoxia. Moreover, SAH-N excels in sensitivity, selectivity and stability, and successes to visualize the presence of CO on zebrafishes. We expect that the silicone fluorescent probe SAN-H will contribute to the further application of the in situ CO detection in biological systems.
G-quadruplex (G4), an important secondary structure of nucleic acids, is polymorphic in structure. G4 monomers can associate with each other to form multimers, which show better application performance than monomers in some aspects. G4 dimers, the simplest and most widespread multimeric structures, are often used as a representative for studying multimers. RHAU, a G4 ligand, has been reported to recognize G4 dimers. However, there are few reports focusing on interactions between RHAU and different G4 dimers. In this work, interactions between RHAU peptide and six G4 dimers were investigated by size-exclusion chromatography (SEC). It was revealed that compared to the hybrid G4 monomer, the hybrid tandem unstacked G4 dimer could form special binding sites, leading to a weak interaction with RHAU. It was also found that the steric hindrance at terminal G-tetrads of a special Z-G4 structure greatly weakened their interactions with RHAU. Additionally, RHAU exhibited stronger interactions with intermolecular stacked/interlocked parallel dimers than with intramolecular tandem stacked parallel dimers. This work enriches the understanding of interactions between RHAU and G4 dimers, which is conducive to the elucidation of G4 polymorphism, and provides a strong reference for studying G4 multimer–peptide interactions.
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