Improved lung cancer classification by employing diverse molecular features of microRNAs.

MiRNAs are edited or modified in multiple ways during their biogenesis pathways. It was reported that miRNA editing was deregulated in tumors, suggesting the potential value of miRNA editing in cancer classification. Here we extracted three types of miRNA features from 395 LUAD and control samples, including the abundances of original miRNAs, the abundances of edited miRNAs, and the editing levels of miRNA editing sites. Our results show that eight classification algorithms selected generally had better performances on combined features than on the abundances of miRNAs or editing features of miRNAs alone. One feature selection algorithm, i.e., the DFL algorithm, selected only three features, i.e., the frequencies of hsa-miR-135b-5p, hsa-miR-210-3p and hsa-mir-182_48u (an edited miRNA), from 316 training samples. Seven classification algorithms achieved 100% accuracies on these three features for 79 independent testing samples. These results indicate that the additional information of miRNA editing is useful in improving the classification of LUAD samples.

Phased secondary small interfering RNAs in Camellia sinensis var. assamica.

Phased secondary small interfering RNAs (phasiRNAs) in plants play important roles in regulating genome stability, plant development and stress adaption. Camellia sinensis var. assamica has immense economic, medicinal and cultural significance. However, there are still no studies of phasiRNAs and their putative functions in this valuable plant. We identified 476 and 43 PHAS loci which generated 4290 twenty one nucleotide (nt) and 264 twenty four nt phasiRNAs, respectively. Moreover, the analysis of degradome revealed more than 35000 potential targets for these phasiRNAs. We identified several conserved 21 nt phasiRNA generation pathways in tea plant, including miR390 → TAS3, miR482/miR2118 → NB-LRR, miR393 → F-box, miR828 → MYB/TAS4, and miR7122 → PPR in this study. Furthermore, we found that some transposase and plant mobile domain genes could generate phasiRNAs. Our results show that phasiRNAs target genes in the same family in cis- or trans-manners, and different members of the same gene family may generate the same phasiRNAs. The phasiRNAs, generated by transposase and plant mobile domain genes, and their targets, suggest that phasiRNAs may be involved in the inhibition of transposable elements in tea plant. To summarize, these results provide a comprehensive view of phasiRNAs in Camellia sinensis var. assamica.

Identification of microRNA editing sites in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a malignant tumor originating from the renal tubular epithelium. Although the microRNAs (miRNAs) transcriptome of ccRCC has been extensively studied, the role of miRNAs editing in ccRCC is largely unknown. By analyzing small RNA sequencing profiles of renal tissues of 154 ccRCC patients and 22 normal controls, we identified 1025 miRNA editing sites from 246 pre-miRNAs. There were 122 editing events with significantly different editing levels in ccRCC compared to normal samples, which include two A-to-I editing events in the seed regions of hsa-mir-376a-3p and hsa-mir-376c-3p, respectively, and one C-to-U editing event in the seed region of hsa-mir-29c-3p. After comparing the targets of the original and edited miRNAs, we found that hsa-mir-376a-1_49g, hsa-mir-376c_48g and hsa-mir-29c_59u had many new targets, respectively. Many of these new targets were deregulated in ccRCC, which might be related to the different editing levels of hsa-mir-376a-3p, hsa-mir-376c-3p, hsa-mir-29c-3p in ccRCC compared to normal controls. Our study sheds new light on miRNA editing events and their potential biological functions in ccRCC.

MicroRNAs in Extracellular Vesicles of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease with dysfunction of memory, language and thinking. More than 55 million people were diagnosed with AD or other dementia around the world in 2020. The pathology of AD is still unclear and there are no applicable therapies for AD. MicroRNAs (miRNAs) play key roles in AD pathology and have great potential for the diagnosis and treatment of AD. Extracellular vesicles (EVs) widely exist in body fluids such as blood and cerebrospinal fluid (CSF) and contain miRNAs that are involved in cell-to-cell communication. We summarized the dysregulated miRNAs in EVs derived from the different body fluids of AD patients, as well as their potential function and application in AD. We also compared these dysregulated miRNAs in EVs to those in the brain tissues of AD patients aiming to provide a comprehensive view of miRNAs in AD. After careful comparisons, we found that miR-125b-5p and miR-132-3p were upregulated and downregulated in several different brain tissues of AD and EVs of AD, respectively, suggesting their value in AD diagnosis based on EV miRNAs. Furthermore, miR-9-5p was dysregulated in EVs and different brain tissues of AD patients and had also been tested as a potential therapy for AD in mice and human cell models, suggesting that miR-9-5p could be used to design new therapies for AD.

Identification of microRNA editing sites in three subtypes of leukemia.

Leukemia is an aberrant hyper-proliferation of immature blood cells that do not form solid tumors. The transcriptomes of microRNAs (miRNAs) of leukemia have been intensively explored. However, miRNA editing of leukemia has not been extensively studied. To identify miRNA editing patterns and explore their functional relevance in leukemia, we analyzed 200 small RNA sequencing profiles of three subtypes of leukemia and identified hundreds of miRNA editing sites in three subtypes of leukemia. Then, we compared the editing levels of identified miRNA editing sites in leukemia and normal controls. Many miRNAs were differential edited in different subtypes of leukemia. We also found the editing levels of 3'-A editing sites of hsa-mir-21-5p and hsa-mir-155-5p decreased in chronic lymphocytic leukemia patients with radiation treatments. By integrating PAR-CLIP sequencing profiles, we predicted the targets of original and edited miRNAs. One of the edited miRNA, hsa-let-7b_5c, with an additional cytosine at 5' end of hsa-let-7b-5p, potentially targeted VBP1 and CTDSP1. CTDSP1 was significantly downregulated in T-ALL compared to normal controls, which might be originated from the hyperediting of hsa-let-7b-5p in T-ALL. Our study provides a comprehensive view of miRNA editing in three different subtypes of leukemia.

Case report: A heterozygous mutation in ZNF462 leads to growth hormone deficiency.

Weiss-Kruszka syndrome (WSKA) is a rare disease most often caused by mutations in the ZNF462 gene. To screen for hereditary diseases, exons from the patient's genome were sequenced. Genomic PCR experiments followed by Sanger sequencing were used to confirm the mutated genomic regions in the patient and his parents. We report a new mutation site, a heterozygous mutation (NM_021224.6:c.6311dup) in ZNF462 in a male patient of 8 years old. The mutation in the ZNF462 gene caused WSKA. This patient is the first case with WSKA characterized by attention-deficit hyperactivity disorder and complete growth hormone deficiency without pituitary lesions. Our results suggest that the heterozygous mutation in ZNF462 is the direct cause of WSKA in this patient. Mutations in other genes interacting with ZNF462 result in similar symptoms of WSKA. Furthermore, ZNF462 and its interacting proteins ASXL2 and VPS13B may form a protein complex that is important for normal development but awaits more studies to reveal its detailed functions.

Modelling the octanol-air partition coefficient of aromatic pollutants based on the solvation free energy and the dimer effect.

In this study, generalized predictive models were developed to estimate KOA of four kinds of aromatic pollutants based on the calculated solvation free energy and taking the dimer effect into account. Uncorrected log KOA values, which were directly estimated from the calculated solvation free energy of individual molecules, underestimated experimental values, and the deviation increased with increasing log KOA. Dimers were found to greatly affect the apparent KOA values of these aromatic pollutants, which were driven by π-π interactions. London dispersion and exchange-repulsion terms were identified to be dominant components of the underlying π-π interactions. It is interesting to find that the π-π interactions of polybrominated diphenyl ethers correlate with not only the molecular polarizability but also the size of opposing aromatic surfaces, which leads to a different trend of π-π interactions from other aromatic pollutants. A universal quantitative structure-activity relationship model was developed to estimate the proportion of dimers based on five molecular structural descriptors relevant to the π-π interactions. After calibration with the dimer effect, estimations of log KOA were consistent with experimental values. Therefore, the dimer effect should be taken into consideration when investigating the partition behavior of aromatic pollutants, and the solvation free energy model could be an alternative method for the prediction of KOA.

MicroRNA editing patterns in Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disease. MicroRNAs (miRNAs) are small non-coding RNAs that mediate post-transcriptional regulation of target genes. Although miRNAs are extensively edited in human brains, the editome of miRNAs in brains of HD patients is largely unknown. By analyzing the small RNA sequencing profiles of brain tissues of 28 HD patients and 83 normal controls, 1182 miRNA editing sites with significant editing levels were identified. In addition to 27 A-to-I editing sites, we identified 3 conserved C-to-U editing sites in miRNAs of HD patients. 30 SNPs in the miRNAs of HD patients were also identified. Furthermore, 129 miRNA editing events demonstrated significantly different editing levels in prefrontal cortex samples of HD patients (HD-PC) when compared to those of healthy controls. We found that hsa-mir-10b-5p was edited to have an additional cytosine at 5'-end in HD-PC, and the edited hsa-mir-10b repressed GTPBP10 that was often downregulated in HD. The down-regulation of GTPBP10 might contribute to the progression of HD by causing gradual loss of function of mitochondrial. These results provide the first endeavor to characterize the miRNA editing events in HD and their potential functions.

Sorptive removal of methylene blue from water by magnetic multi-walled carbon nanotube composites.

In the present study, five magnetic multi-walled carbon nanotubes (MMWCNTs) with different diameters were prepared and their performance on the sorptive removal of methylene blue (MB) from water was investigated. Transmission electron microscope, scanning electron microscope, Fourier transform infrared spectrometer, X-ray diffraction, and vibrating sample magnetometer confirm that the surface of these MMWCNTs has been decorated by Fe3O4 nanoparticles, which renders the MMWCNTs superparamagnetic. Thus, these MMWCNTs can be easily separated from water after the adsorption. During the adsorption process, pH slightly affected the removal efficiency of MB and the adsorption performed better under weak alkaline conditions. Adsorption kinetics followed the pseudo-second-order kinetic model well, and the Dubinin-Radushkevich model fitted the isotherms best. The maximum adsorption capacity for MB reached 204.2 mg/g, and the values decreased with increasing diameters of MMWCNTs due to decreasing specific surface areas. The thermodynamics parameters indicated the spontaneous and exothermic nature of the adsorption. The reusability test showed that MMWCNTs could be used for 6 cycles without significant loss of the adsorption capacity. And common ions (K+, Na+, Ca2+ and Al3+) and SDS in water did not show greatly effects on the removal efficiency of MB. Hence, MMWCNTs prepared in this study could be promising adsorbents for dyes removal from wastewater.

Recent Progress on Relevant microRNAs in Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose pathogenesis is unclear and is affected by both genetic and environmental factors. The microRNAs (miRNAs) are a kind of single-stranded non-coding RNA with 20-22 nucleotides, which normally inhibit their target mRNAs at a post-transcriptional level. miRNAs are involved in almost all biological processes and are closely related to ASD and many other diseases. In this review, we summarize relevant miRNAs in ASD, and analyze dysregulated miRNAs in brain tissues and body fluids of ASD patients, which may contribute to the pathogenesis and diagnosis of ASD.

Generation and properties of aqu/nC60: the combined effects of humic acid, sunlight, and agitation intensity.

Once released into natural water, the environmental behavior and fate of C60 could inevitably been affected by humic acid (HA), sunlight, and hydrodynamic conditions. However, the combined effects of these factors are not so clear. Therefore, in the present study, effects of HA, sunlight, and agitation intensity on generation and properties of aqu/nC60 were investigated. The results indicated that HA could increase the concentration of aqu/nC60 mainly through the steric hindrance effect. The higher agitation intensity led to higher concentrations of aqu/nC60 and more efficient steric stabilization was formed by HA. Sunlight irradiation promoted the surface oxidization and consequently enhanced the dispersion of C60. The relative order of the influence on the UV/vis concentration was sunlight > agitation intensity > HA. In addition, HA might not always enhance the dispersion of aqu/nC60 due to light screening/ROS scavenging, over-coating, or chain-like bridging mechanism. Therefore, evaluating the environmental behavior and fate of C60 should take these factors into account together.

Prediction of octanol-air partition coefficients for PCBs at different ambient temperatures based on the solvation free energy and the dimer ratio.

Temperature-dependent octanol-air partition coefficients (KOA) are of great importance in assessing the environmental behavior and fate of persistent organic pollutants including polychlorinated biphenyls (PCBs). Due to the tremendous amounts of time, effort and cost needed for the experimental determination of KOA, it is desirable to develop a rapid and precise predictive method to estimate KOA just based on molecular structure. In the present study, a predictive model for log KOA of PCBs at ambient temperatures was developed based on the thermodynamic relationship between KOA and the solvation free energy from air to octanol (ΔGOA). For the calculation of ΔGOA of PCBs, the optimal combination of theoretical method and basis-set was identified to be HF/MIDI!6D for both geometry optimization and energy calculation. Dimer formation could affect the partition behavior and promote the apparent KOA values of PCBs. After taking the effect of dimer formation into account, the goodness-of-fit, predictive ability, and robustness of the predictive model were significantly improved. Apparent log KOA values of PCBs at different ambient temperatures ranging from 283.15 to 303.15 K were predicted. Compared with other reported models, the model developed in the present study had not only comparable goodness-of-fit and predictive ability, but also a universal application domain and the relative independency of experimental data. Therefore, the solvation free energy method could be a promising method for the prediction of KOA.