LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer

Long non-coding RNAs (lncRNAs) act as important regulators of tumorigenesis and development in bladder cancer. However, the underlying molecular mechanisms remain elusive. We previously identified a novel lncRNA signature related to immunity and progression in bladder cancer. Here we further explored the function of RP11-89, a lncRNA discovered in the previous signature. Loss- and gain-of function experiments were performed using CCK-8 assay, flow cytometry, Transwell assays, scratch tests and subcutaneous nude mouse models. High-throughput RNA sequencing was conducted to identify dysregulated genes in bladder cancer cells with RP11-89 knockdown or overexpression. Regulation of RP11-89 on miR-129-5p and PROM2 was explored through luciferase reporter assay, RIP assay and RNA pull-down assay. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. We found that RP11-89 “sponges” miR-129-5p and upregulates PROM2. Elevated PROM2 in cells was associated with attenuated ferroptosis through iron export, formation of multivesicular bodies and less mitochondrial abnormalities. We demonstrated that RP11-89 is a novel tumorigenic regulator that inhibits ferroptosis via PROM2-activated iron export. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer.Subject terms: Tumour biomarkers, Tumour biomarkers     

Network-based Phenome-Genome Association Prediction by Bi-Random Walk

MotivationThe availability of ontologies and systematic documentations of phenotypes and their genetic associations has enabled large-scale network-based global analyses of the association between the complete collection of phenotypes (phenome) and genes. To provide a fundamental understanding of how the network information is relevant to phenotype-gene associations, we analyze the circular bigraphs (CBGs) in OMIM human disease phenotype-gene association network and MGI mouse phentoype-gene association network, and introduce a bi-random walk (BiRW) algorithm to capture the CBG patterns in the networks for unveiling human and mouse phenome-genome association. BiRW performs separate random walk simultaneously on gene interaction network and phenotype similarity network to explore gene paths and phenotype paths in CBGs of different sizes to summarize their associations as predictions.ResultsThe analysis of both OMIM and MGI associations revealed that majority of the phenotype-gene associations are covered by CBG patterns of small path lengths, and there is a clear correlation between the CBG coverage and the predictability of the phenotype-gene associations. In the experiments on recovering known associations in cross-validations on human disease phenotypes and mouse phenotypes, BiRW effectively improved prediction performance over the compared methods. The constructed global human disease phenome-genome association map also revealed interesting new predictions and phenotype-gene modules by disease classes.     

Town Mouse or Country Mouse: Identifying a Town Dislocation Effect in Chinese Urbanization

Understanding urbanization and evaluating its impact are vital for formulating global sustainable development. The results obtained from evaluating the impact of urbanization, however, depend on the kind of measurement used. With the goal of increasing our understanding of the impact of urbanization, we developed direct and indirect subjective indicators to measure how people assess their living situation. The survey revealed that the projected endorsements and perceived social ambiance of people toward living in different types of settlements did not improve along with the urbanization level in China. The assessment scores from the city dwellers were not significantly different from those from the country areas and, more surprisingly, both were significantly higher than the assessment scores of the town dwellers, which we had expected to fall between the assessment scores of the country and city dwellers. Instead their scores were the lowest. We dubbed this V-shaped relationship the “town dislocation effect.” When searching for a potential explanation for this effect, we found additional town dislocation effects in social support, loss aversion, and receptivity toward genetically modified food. Further analysis showed that only social support mediated the relationship between the three tiers of settlements (cities, country areas, and towns) and the subjective indicator. The projected endorsements yielded significant subjective assessments that could enhance our understanding of Chinese urbanization. Towns posed specific problems that require special attention.     

Thin‐Film Solar Cells with InP Absorber Layers Directly Grown on Nonepitaxial Metal Substrates

The design and performance of solar cells based on InP grown by the nonepitaxial thin‐film vapor–liquid–solid (TF‐VLS) growth technique is investigated. The cell structure consists of a Mo back contact, p‐InP absorber layer, n‐TiO₂ electron selective contact, and indium tin oxide transparent top electrode. An ex situ p‐doping process for TF‐VLS grown InP is introduced. Properties of the cells such as optoelectronic uniformity and electrical behavior of grain boundaries are examined. The power conversion efficiency of first generation cells reaches 12.1% under simulated 1 sun illumination with open‐circuit voltage (V_OC) of 692 mV, short‐circuit current (J_SC) of 26.9 mA cm^?2, and fill factor (FF) of 65%. The FF of the cell is limited by the series resistances in the device, including the top contact, which can be mitigated in the future through device optimization. The highest measured V_OC under 1 sun is 692 mV, which approaches the optically implied V_OC of ≈795 mV extracted from the luminescence yield of p‐InP.     

Trace analysis of N‐acetyl‐L‐cysteine using luminol–H2O2 chemiluminescence system catalyzed by silver nanoparticles

N‐Acetyl‐L‐cysteine (NAC) can inhibit the luminol–H₂O₂, reaction, which is catalyzed by silver nanoparticles. Based on this phenomenon a new method was developed for NAC determination. Under optimum conditions, a linear relationship between chemiluminescence intensity and NAC concentration was found in the range 0.034–0.98 µg/mL. The detection limit was 0.010 µg/mL (S/N =3), and the relative standard deviation (RSD) was <5% for 0.480 µg/mL NAC (n =5). This simple, sensitive and inexpensive method has been applied to measure the concentration of NAC in pharmaceutical tablets. Copyright © 2014 John Wiley & Sons, Ltd.     

Study on the interaction of a cyanine dye with human serum transferrin

Complexation between the primary carrier of ligands in blood plasma, human serum transferrin (Tf), and a cyanine dye, 3,3′‐di(3‐sulfopropyl)‐4,5,4′,5′‐dibenzo‐9‐phenyl‐thiacarbocyanine‐triethylam monium salt (PTC) was investigated using fluorescence spectra, UV/Vis absorption spectra, synchronous fluorescence spectra, circular dichroism (CD) and molecular dynamic docking. The experimental results demonstrate that the formation of PTC–Tf complex is stabilized by van der Waal's interactions and hydrogen bonds, and the binding constants were found to be 8.55 × 10⁶, 8.19 × 10⁶ and 1.75 × 10⁴ M^?1. Moreover, fluorescence experiments prove that the operational mechanism for the fluorescence quenching is static quenching and non‐radiative energy transfer. Structural investigation of the PTC–Tf complexes via synchronous fluorescence spectra and CD showed that the structure of Tf became more stable with a major increase in the α‐helix content and increased polarity around the tryptophan residues after PTC binding. In addition, molecular modeling highlights the residues located in the N‐lobe, which retain high affinity for PTC. The mode of action of the PTC–Tf complex is illustrated by these results, and may provide an effective pathway for the transport and targeted delivery of antitumor agents. Copyright © 2015 John Wiley & Sons, Ltd.     

Engineering surface hydrophobicity improves activity of Bacillus thermocatenulatus lipase 2 enzyme

Bacillus thermocatenulatus lipase 2 (BTL2) is a promising industrial enzyme used in biodiesel production. Although BTL2 has high thermostability and good resistance to organic solvents, the activity of BTL2 is suboptimal for industrial processes. To improve BTL2 activity, we engineered BTL2 lipase by modulating hydrophobicity of its lid domain. Through site‐directed mutagenesis, we constructed three mutants, namely Y225F+S232A, S232A+T236V and Q185L, to cover all uncharged hydrophilic amino acids within the lid domain. Activities of these mutants were characterized. Our findings suggest that one mutant (Y225F+S232A) showed ～35% activity increase in catalyzing heterogeneous hydrolytic reactions relevant for industrial applications. A mathematical framework was established to account for different molecular events that contribute to the observed apparent catalytic activities. Increases in hydrophobicity of lid domains were associated with increased interfacial adsorption of lipases and lower molecular enzymatic activities. The measured apparent activities of lipases include contributions from both events. Lid hydrophobicity can thus result in different changes in lipase activities depending on the mutation site. Our work demonstrates the feasibility of increasing BTL2 activity by modulating the hydrophobicity of lid domains and provides some guidelines for further improving BTL2 activity.     

Bis‐ and Tetrakis(carboxylato)platinum(IV) Complexes with Mixed Axial Ligands – Synthesis,Characterization, and Cytotoxicity

A series of twelve novel diamminetetrakis(carboxylato)platinum(IV) and 18 novel bis(carboxylato)dichlorido(ethane‐1,2‐diamine)platinum(IV) complexes with mixed axial carboxylato ligands was synthesized and characterized by multinuclear ¹H‐, ¹³C‐, ¹⁵N‐, and ¹⁹⁵Pt‐NMR spectroscopy. Their cytotoxic potential was evaluated (by MTT assay) against three human cancer cell lines derived from ovarian teratocarcinoma (CH1/PA‐1), lung (A549), and colon carcinoma (SW480). In the cisplatin‐sensitive CH1/PA‐1 cancer cell line, diamminetetrakis(carboxylato)platinum(IV) complexes showed IC₅₀ values in the low micromolar range, whereas, for the most lipophilic compounds of the bis(carboxylato)dichlorido(ethane‐1,2‐diamine)platinum(IV) series, IC₅₀ values in the nanomolar range were found.