RNA-binding proteins (RBPs) regulate the expression of thousands of transcripts, and some are reported to be involved in human tumorigenesis. However, little is known about the dysregulation of RBPs at the genomic level in human cancers. Here, we conducted comprehensive analyses for expression, somatic copy number alteration (SCNA), and mutation profiles of 1,542 RBPs in ∼7,000 clinical specimens across 15 cancer types. We identified markedly dysregulated RBPs and found that downregulation was a predominant pattern in cancer. Combined with recurrent SCNA data, we identified 76 RBPs as potential drivers. We also discovered a set of 139 RBPs that were significantly mutated in cancers. We confirmed the oncogenic property of six RBPs in colorectal and liver cancer cell lines by using in vitro functional experiments. Our study highlights the potential roles of RBPs in carcinogenesis and lays the groundwork to better understand the functions and mechanisms of RBPs in cancer.

Small non-coding RNAs (e.g. miRNAs) and long non-coding RNAs (e.g. lincRNAs and circRNAs) are emerging as key regulators of various cellular processes. However, only a very small fraction of these enigmatic RNAs have been well functionally characterized. In this study, we describe deepBase v2.0 (http://biocenter.sysu.edu.cn/deepBase/), an updated platform, to decode evolution, expression patterns and functions of diverse ncRNAs across 19 species. deepBase v2.0 has been updated to provide the most comprehensive collection of ncRNA-derived small RNAs generated from 588 sRNA-Seq datasets. Moreover, we developed a pipeline named lncSeeker to identify 176 680 high-confidence lncRNAs from 14 species. Temporal and spatial expression patterns of various ncRNAs were profiled. We identified approximately 24 280 primate-specific, 5193 rodent-specific lncRNAs, and 55 highly conserved lncRNA orthologs between human and zebrafish. We annotated 14 867 human circRNAs, 1260 of which are orthologous to mouse circRNAs. By combining expression profiles and functional genomic annotations, we developed lncFunction web-server to predict the function of lncRNAs based on protein-lncRNA co-expression networks. This study is expected to provide considerable resources to facilitate future experimental studies and to uncover ncRNA functions.

Pt-based alloy nanocrystals have shown great success in oxygen reduction electrocatalysis owing to their unique surface and electronic structures. However, they suffer from severe stability issues due to the dissolution of non-noble metal elements, leading to the "trade-off " between activity and stability. In this work, targeting the stability issue of a Pt x Cu y -based alloy, Pt 2 CuW 0.25 ternary alloy nanoparticles are synthesized by thermal reduction strategy based on wet-chemical method using W(CO) 6 as a reductant. Apart from the competitive activity, the obtained Pt 2 CuW 0.25 /C shows remarkable stability, whereby the area specific activity and mass activity maintain 89.5% and 95.9% of the initial values, respectively, after 30 000 cycles of accelerated polarization between 0.6 and 1.1 V (vs reversible hydrogen electrode). By using vacancy formation energy of surface Pt as the descriptor, it is found that the enhanced stability of Pt 2 CuW 0.25 /C originates mainly from the stronger bonding between W and Pt/Cu atoms, acting as an "adhesive" to stabilize the atoms from dissolution, which is further verified by chemical stability experiments. This work demonstrates a rational design strategy for ternary alloy nano-electrocatalyst that has high thermodynamic stability while maintaining high activity by employing high-melting-point metal.

Long non-coding RNAs (lncRNAs) are emerging as important regulatory molecules in developmental, physiological, and pathological processes. However, the precise mechanism and functions of most of lncRNAs remain largely unknown. Recent advances in high-throughput sequencing of immunoprecipitated RNAs after cross-linking (CLIP-Seq) provide powerful ways to identify biologically relevant protein–lncRNA interactions. In this study, by analyzing millions of RNA-binding protein (RBP) binding sites from 117 CLIP-Seq datasets generated by 50 independent studies, we identified 22,735 RBP–lncRNA regulatory relationships. We found that one single lncRNA will generally be bound and regulated by one or multiple RBPs, the combination of which may coordinately regulate gene expression. We also revealed the expression correlation of these interaction networks by mining expression profiles of over 6000 normal and tumor samples from 14 cancer types. Our combined analysis of CLIP-Seq data and genome-wide association studies data discovered hundreds of disease-related single nucleotide polymorphisms resided in the RBP binding sites of lncRNAs. Finally, we developed interactive web implementations to provide visualization, analysis, and downloading of the aforementioned large-scale datasets. Our study represented an important step in identification and analysis of RBP–lncRNA interactions and showed that these interactions may play crucial roles in cancer and genetic diseases.

incandescent lamp or fluorescent lamp and also as backlights for liquid crystal displays (LCDs) applications. [1] The most typical approach to generating white light is by uniting a blue or UV (ultraviolet) LED chip and one or more phosphors that can be pumped by the excitation light source. [2] Therefore, it is important to exploit "good" phosphors for LEDs application which meet the application demands simultaneously: i) high photoluminescence (PL) quantum efficiency (QE) and emission intensity; ii) excellent thermal quenching (TQ) property especially for the high power condition or laser LEDs; and iii) controlled excitation/emission property to fulfill different application requirements including the full-spectrum lighting, special light source or display. [3] The most common approach to developing new phosphors is by selecting suitable inorganic matrices and doped activators. [4] However, this way is difficult because new inorganic hosts become rare and their luminescence properties are also hardly predictable. Recently, learning from a mineral structure to develop appropriate matrices for new phosphors as Phosphor-converted white light-emitting diodes (LEDs) are currently playing key roles in the lighting and display industries and trigger urgent demands for the discovery of "good" phosphors with high quantum efficiency, improved thermal stability, and controllable excitation/emission properties. Herein, a general and efficient heterovalent substitution strategy is demonstrated in K 2 HfSi 3 O 9 :Eu 2+ achieved by Ln 3+ (Ln = Gd, Tb, Dy, Tm, Yb, and Lu) doping to optimize luminescence properties, and as an example, the Lu 3+ substitution leads to improvement of emission intensity and thermal stability, as well as tunable emission color from blue to cyan. The structural stability and Eu 2+ occupation via Lu 3+ doping have been revealed by the structural elaboration and density functional theory calculations, respectively. It is shown that heterovalent substitution allows predictive control of site preference of luminescent centers and therefore provides a new method to optimize the solid-state phosphors for LEDs.

STUDY QUESTION Whether the testis-specific extracellular vesicle (EV) long noncoding RNAs (lncRNAs) in seminal plasma could be utilized to predict the presence of testicular spermatozoa in nonobstructive azoospermia (NOA) patients? SUMMARY ANSWER Our findings indicate that the panel based on seminal plasma EV lncRNAs was a sensitive and specific method in predicting the presence of testicular spermatozoa and may improve clinical decision-making of NOA. WHAT IS KNOWN ALREADY The adoption of sperm retrieval techniques, especially microdissection testicular sperm extraction (mTESE), in combination with ICSI has revolutionized treatment for NOA. However, there are no precise and noninvasive methods for predicting whether there are testicular spermatozoa in NOA patients before mTESE. STUDY DESIGN, SIZE, DURATION RNA sequencing was performed on seminal plasma EVs from 6 normozoospermic men who underwent IVF due to female factor and 5 idiopathic NOA patients who failed to obtain testicular spermatozoa by mTESE and were diagnosed as having Sertoli cell-only syndrome by postoperative pathology. A biomarker panel of lncRNAs was constructed and verified in 96 NOA patients who underwent mTESE. Decision-making process was established based on the panel in seminal plasma EVs from 45 normozoospermia samples, 43 oligozoospermia samples, 62 cryptozoospermia samples, 96 NOA samples. PARTICIPANTS/MATERIALS, SETTING, METHODS RNA sequencing was done to examine altered profiles of EV lncRNAs in seminal plasma. Furthermore, a panel consisting of EV lncRNAs was established and evaluated in training set and validation sets. MAIN RESULTS AND THE ROLE OF CHANCE A panel consisting of nine differentially expressed testis-specific lncRNAs, including LOC100505685, SPATA42, CCDC37-DT, GABRG3-AS1, LOC440934, LOC101929088 (XR_927561.2), LOC101929088 (XR_001745218.1), LINC00343 and LINC00301, was established in the training set and the AUC was 0.986. Furthermore, the AUC in the validation set was 0.960. Importantly, the panel had a unique advantage when compared with models based on serum hormones from the same group of NOA cases (AUC, 0.970 vs 0.723; 0.959 vs 0.687, respectively). According to the panel of lncRNAs, a decision-making process was established, that is when the score of an NOA case exceeds 0.532, sperm retrieval surgery may be recommended. LIMITATIONS, REASONS FOR CAUTION In the future, the sample size needs to be further expanded. Meanwhile, the regulatory functions and mechanism of lncRNAs in spermatogenesis also need to be elucidated. WIDER IMPLICATIONS OF THE FINDINGS When the score of our panel is below 0.532, subjecting the NOA patients to ineffective surgical interventions may not be recommended due to poor sperm retrieval rate. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Natural Science Foundation of China (81871110, 81971314 and 81971759); the Guangdong Special Support Plan-Science and Technology Innovation Youth Top Talents Project (2016TQ03R444); the Science and Technology Planning Project of Guangdong Province (2016B030230001 and 201707010394); the Key Scientific and Technological Program of Guangzhou City (201604020189); the Pearl River S&T Nova Program of Guangzhou (201806010089); the Transformation of Scientific and Technological Achievements Project of Sun Yat-sen University (80000-18843235) and the Youth Teacher Training Project of Sun Yat-sen University (17ykpy68 and 18ykpy09). There are no competing interests related to this study. TRIAL REGISTRATION NUMBER N/A.

Although thousands of pseudogenes have been annotated in the human genome, their transcriptional regulation, expression profiles and functional mechanisms are largely unknown. In this study, we developed dreamBase (http://rna.sysu.edu.cn/dreamBase) to facilitate the investigation of DNA modification, RNA regulation and protein binding of potential expressed pseudogenes from multidimensional high-throughput sequencing data. Based on ∼5500 ChIP-seq and DNase-seq datasets, we identified genome-wide binding profiles of various transcription-associated factors around pseudogene loci. By integrating ∼18 000 RNA-seq data, we analysed the expression profiles of pseudogenes and explored their co-expression patterns with their parent genes in 32 cancers and 31 normal tissues. By combining microRNA binding sites, we demonstrated complex post-transcriptional regulation networks involving 275 microRNAs and 1201 pseudogenes. We generated ceRNA networks to illustrate the crosstalk between pseudogenes and their parent genes through competitive binding of microRNAs. In addition, we studied transcriptome-wide interactions between RNA binding proteins (RBPs) and pseudogenes based on 458 CLIP-seq datasets. In conjunction with epitranscriptome sequencing data, we also mapped 1039 RNA modification sites onto 635 pseudogenes. This database will provide insights into the transcriptional regulation, expression, functions and mechanisms of pseudogenes as well as their roles in biological processes and diseases.

AbstractsStress, including both psychological and physical stimulation, can cause changes in the microbiota and mucosal function of the gastrointestinal system. There are few research studies available about the faecal microbiota changes after stress, such as water immersion restraint stress (WIRS). Therefore, in this study, we focused on analysing the composition changes of faecal microbiota in WIRS mice. The WIRS model, in which Blab/c mice were immersed in 21 ± 2 °C water for 4 h each day for 14 days, was established. Behavioural changes, the serum levels of corticosterone, IFN-γ and IL-17 and gastric mucosal injury were also assessed. Ten faecal microbiota samples were detected by Illumina Miseq sequencing of the 16S rRNA genes from 367205 characterised sequences. Finally, we find significant differences in the faecal microbiota composition between the control and the WIRS groups. There was an obvious increase in Lachnospiraceae in the WIRS mice (p = 0.0286, p < 0.05), which is associated with human diseases, such as ulcerative colitis, Crohn’s and celiac disease. Our research indicates that stress changes in the faecal microbiota. These results suggest that observing shifts of the intestinal microbiota is a promising method to explore the mechanism of the stress associated with gastrointestinal diseases and to provide us with a better understanding of the relationship between the microbiota and disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13568-017-0383-4) contains supplementary material, which is available to authorized users.