tModBase: deciphering the landscape of tRNA modifications and their dynamic changes from epitranscriptome data.

tRNA molecules contain dense, abundant modifications that affect tRNA structure, stability, mRNA decoding and tsRNA formation. tRNA modifications and related enzymes are responsive to environmental cues and are associated with a range of physiological and pathological processes. However, there is a lack of resources that can be used to mine and analyse these dynamically changing tRNA modifications. In this study, we established tModBase (https://www.tmodbase.com/) for deciphering the landscape of tRNA modification profiles from epitranscriptome data. We analysed 103 datasets generated with second- and third-generation sequencing technologies and illustrated the misincorporation and termination signals of tRNA modification sites in ten species. We thus systematically demonstrate the modification profiles across different tissues/cell lines and summarize the characteristics of tRNA-associated human diseases. By integrating transcriptome data from 32 cancers, we developed novel tools for analysing the relationships between tRNA modifications and RNA modification enzymes, the expression of 1442 tRNA-derived small RNAs (tsRNAs), and 654 DNA variations. Our database will provide new insights into the features of tRNA modifications and the biological pathways in which they participate.

tsRFun: a comprehensive platform for decoding human tsRNA expression, functions and prognostic value by high-throughput small RNA-Seq and CLIP-Seq data.

tRNA-derived small RNA (tsRNA), a novel type of regulatory small noncoding RNA, plays an important role in physiological and pathological processes. However, the understanding of the functional mechanism of tsRNAs in cells and their role in the occurrence and development of diseases is limited. Here, we integrated multiomics data such as transcriptome, epitranscriptome, and targetome data, and developed novel computer tools to establish tsRFun, a comprehensive platform to facilitate tsRNA research (http://rna.sysu.edu.cn/tsRFun/ or http://biomed.nscc-gz.cn/DB/tsRFun/). tsRFun evaluated tsRNA expression profiles and the prognostic value of tsRNAs across 32 types of cancers, identified tsRNA target molecules utilizing high-throughput CLASH/CLEAR or CLIP sequencing data, and constructed the interaction networks among tsRNAs, microRNAs, and mRNAs. In addition to its data presentation capabilities, tsRFun offers multiple real-time online tools for tsRNA identification, target prediction, and functional enrichment analysis. In summary, tsRFun provides a valuable data resource and multiple analysis tools for tsRNA investigation.

Novel Optical Modulator Photonic Device Based on TiN/Ti3C2 Heterojunction.

Due to the ability of optical modulators to achieve rapid modulation of optical signals, meeting the demands of high-speed data transmission, modulators based on different novel nanomaterials have become one of the research hotspots over the past dacade. Recently, TiN/Ti3C2 heterojunction exhibits highly efficient thermo-optic performance and extremely strong stability. Therefore, we have demonstrated an all-optical modulator based on the principle of Michelson interference and the thermo-optic effect in this paper. The modulator employs a TiN/Ti3C2 heterojunction-coated microfiber (THM) and further demonstrates its ability to generate phase shifts through an ASE light source. The modulator, with a phase shift slope of 0.025π/mW, can also convert the phase shifts of signal light into amplitude modulation through Michelson interference. The fixed signal light wavelength is 1552.09 nm, and the modulation depth is stable at about 26.4 dB within a wavelength detuning range of -10 to 6 nm; The waveforms of signal light at modulation rates of 500 Hz, 1000 Hz, 2000 Hz, and 3000 Hz were tested, and a 3 dB modulation bandwidth of 2 kHz was measured. The all-optical modulator based on THM has the advantages of high efficiency and stability and has broad application prospects in the fields of all-optical signal processing and high-speed optical communication.

ColorCells: a database of expression, classification and functions of lncRNAs in single cells.

Although long noncoding RNAs (lncRNAs) have significant tissue specificity, their expression and variability in single cells remain unclear. Here, we developed ColorCells (http://rna.sysu.edu.cn/colorcells/), a resource for comparative analysis of lncRNAs expression, classification and functions in single-cell RNA-Seq data. ColorCells was applied to 167 913 publicly available scRNA-Seq datasets from six species, and identified a batch of cell-specific lncRNAs. These lncRNAs show surprising levels of expression variability between different cell clusters, and has the comparable cell classification ability as known marker genes. Cell-specific lncRNAs have been identified and further validated by in vitro experiments. We found that lncRNAs are typically co-expressed with the mRNAs in the same cell cluster, which can be used to uncover lncRNAs' functions. Our study emphasizes the need to uncover lncRNAs in all cell types and shows the power of lncRNAs as novel marker genes at single cell resolution.

Evaluation of the efficacy of ureteroscopic lithotripsy for proximal impacted ureter stones based on a new scoring standard: a bicentric matched-pair analysis.

OBJECTIVE: To evaluate the clinical efficacy of ureteroscopic lithotripsy (URSL) in the treatment of proximal impacted ureter stones (PIUS) based on a new scoring standard in two medical centers. METHODS: The data of 45 patients with Complicated PIUS (total stone score ≥ 3) and 350 with Simple PIUS (total stone score < 3) who underwent URSL were collected in this retrospective study between January 2015 and June 2022. The definition and scoring standards for preoperative high-risk factors associated with stones included whether the diameter of the stone was > 2 cm, stone density was > 1000 HU, there was a history of lithotripsy, the degree of hydronephrosis was greater than moderate, and there was an infection. Scores for stones were then assigned (yes = 1, no = 0), and the Complicated stone case was defined as a total stone score ≥ 3; the Simple stone case was defined as a total stone score < 3. During the same period, 45 patients were selected from the patients with Simple stone cases as the control group, matched at a 1:1 ratio to index Complicated stone cases with regard to age, sex, and BMI. Perioperative data were compared between the two groups. RESULTS: All 90 operations were successfully completed. Compared to the Simple cases group, the surgical duration of the Complicated group was significantly longer (59.69 ± 28.06 min vs. 73.46 ± 27.12 min, p < 0.05), and stone-free rate (SFR) was significantly lower (88.89 vs. 68.9%, p < 0.05). There was a significant difference in complication rate between the two groups regarding Clavien grade I, II, or III complications (20.0% in Complicated cases group vs. 8.9% in Simple cases group, p = 0.037). As for the length of the hospital stay and the total treatment cost, the two groups have no difference. CONCLUSION: For Simple stone cases, URSL had a better SFR and higher surgical efficacy, whereas complicated stone cases had a high complication rate and long operation time. Thus, we suggest that URSL is the preferred choice for Simple stone cases rather than complicated stone cases.

Nomogram for predicting risk factors of fever in patients with negative preoperative urine culture after retrograde intrarenal surgery.

PURPOSE: To determine the risk factors for postoperative fever after retrograde intrarenal surgery (RIRS) in patients with negative preoperative urine culture (UC), and to establish a nomogram for predicting postoperative fever based on these risk factors. METHODS: This study collected 322 patients with negative UC who received RIRS at the First Affiliated Hospital of Anhui Medical University from March 2019 to May 2022. The study population was divided into a fever group and a non-fever group. The risk factors of postoperative fever were determined by univariate and multivariate logistic regression analyses, and a nomogram was established. The nomogram was evaluated in terms of differentiation, calibration, and clinical practicability. RESULTS: In this study, 47 (14.6%) patients developed a fever after surgery. Multivariate logistic regression analysis showed that for patients with negative preoperative urine culture, urinary leucocyte esterase (P = 0.005), operative time (P = 0.019), and intraoperative hypotension (P = 0.028) were independent risk factors of postoperative fever, and a nomogram was constructed according to the above variables. The area under the curve (AUC) calculated by receiver operating characteristic (ROC) analysis was 0.807 (95% CI 0.739-0.876), indicating good discrimination. The calibration curves showed good consistency, and the clinical decision curve analysis (DCA) showed the clinical applicability of the model. CONCLUSIONS: For patients with negative preoperative urine culture, urine leukocyte esterase, operative time, and intraoperative hypotension are independent risk factors of postoperative fever. The new nomogram can better assess the risk of infection in patients with negative UC after RIRS.

A novel peptide encoded by N6-methyladenosine modified circMAP3K4 prevents apoptosis in hepatocellular carcinoma.

BACKGROUND: Circular RNAs (circRNAs) regulate various biological activities and have been shown to play crucial roles in hepatocellular carcinoma (HCC) progression. However, only a few coding circRNAs have been identified in cancers, and their roles in HCC remain elusive. This study aimed to identify coding circRNAs and explore their function in HCC. METHODS: CircMAP3K4 was selected from the CIRCpedia database. We performed a series of experiments to determine the characteristics and coding capacity of circMAP3K4. We then used in vivo and in vitro assays to investigate the biological function and mechanism of circMAP3K4 and its protein product, circMAP3K4-455aa, in HCC. RESULTS: We found circMAP3K4 to be an upregulated circRNA with coding potential in HCC. IGF2BP1 recognized the circMAP3K4 N6-methyladenosine modification and promoted its translation into circMAP3K4-455aa. Functionally, circMAP3K4-455aa prevented cisplatin-induced apoptosis in HCC cells by interacting with AIF, thus protecting AIF from cleavage and decreasing its nuclear distribution. Moreover, circMAP3K4-455aa was degraded through the ubiquitin-proteasome E3 ligase MIB1 pathway. Clinically, a high level of circMAP3K4 is an independent prognostic factor for adverse overall survival and adverse disease-free survival of HCC patients. CONCLUSIONS: CircMAP3K4 is a highly expressed circRNA in HCC. Driven by m6A modification, circMAP3K4 encoded circMAP3K4-455aa, protected HCC cells from cisplatin exposure, and predicted worse prognosis of HCC patients. Targeting circMAP3K4-455aa may provide a new therapeutic strategy for HCC patients, especially for those with chemoresistance. CircMAP3K4 is a highly expressed circRNA in HCC. Driven by m6A modification, IGF2BP1 facilitates circMAP3K4 peptide translation, then the circMAP3K4 peptide inhibits AIF cleavage and nuclear distribution, preventing HCC cells from cell death under stress and promoting HCC progression.

Nasopharyngeal cancer cell-derived exosomal PD-L1 inhibits CD8+ T-cell activity and promotes immune escape.

Programmed cell death ligand 1 (PD-L1) is an immune surface protein that binds to programmed cell death 1 (PD-1) and allows tumors to evade T-cell immunity. This study aims to define the role of PD-L1 shuttled by tumor cell-derived exosomes in the immune escape of nasopharyngeal carcinoma (NPC). PD-L1 expression was determined in the exosomes isolated from the plasma of NPC patients or from NPC cells. It was found that PD-L1 was highly expressed in the exosomes from the plasma of NPC patients and also in the exosomes from NPC cells. PD-L1/PD-1 binding was identified in the presence or absence of interferon-gamma (IFN-γ) or anti-PD-L1 antibody. PD-L1 expression was elevated following IFN-γ treatment. Binding of PD-L1 to PD-1 was augmented by IFN-γ and blocked by anti-PD-L1 antibody. Following this, CD8+ T cells were sorted out from peripheral blood samples to assess the binding between exosomal PD-L1 and PD-1 on the CD8+ T-cell surface, and to measure the percentage of Ki-67-positive T cells. The results indicated that exosomal PD-L1 bound to the PD-1 on CD8+ T-cell surface, leading to a reduced percentage of Ki-67-positive CD8+ T cells and downregulated production of cytokines. In vivo data confirmed that exosomal PD-L1 promoted NPC tumor growth in mice by suppressing CD8+ T-cell activity. In conclusion, NPC cell-derived exosomes deliver PD-L1 to bind to PD-1 on the CD8+ T-cell surface, through which cytotoxic CD8+ T-cell function was attenuated and the immune escape was thus promoted in NPC.

Floating Ag-NPs@Cu-NW bundles fabricated on copper mesh for highly sensitive SERS detection of uric acid in pretreatment-free urine.

The rapid and sensitive detection of ultra-trace marker molecules from biological samples is of great significance for the wide application of surface-enhanced Raman spectroscopy (SERS) methods in clinical diagnosis and disease monitoring. However, the cumbersome biological sample processing procedures and the poor enrichment of target analytes in hot spots hinder the practical applications of SERS methods. In this paper, we synthesized a novel floating SERS substrate by a simple one-step oxidation process, annealing and in situ chemical etching to form Ag-NPs@Cu-NW bundles on copper mesh (CM). In particular, under spontaneous bottom-up capillary action, the pressure difference at different nanogaps drives uric acid molecules to actively enter hot spots, so that the Ag-NPs@Cu-NW bundle nanostructure with the advantages of a light weight CM is capable of preventing the common coffee-ring effect and enhancing the spatial enrichment of analytes. Therefore, this SERS substrate realizes highly sensitive detection of uric acid at a level of 50 nM in pretreatment-free urine. Currently, this portable, flexible, simple, fast and cost-effective SERS substrate has great potential for early screening and clinical diagnosis of diseases in different biofluids.

The cardiac translational landscape reveals that micropeptides are new players involved in cardiomyocyte hypertrophy.

Hypertrophic growth of cardiomyocytes is one of the major compensatory responses in the heart after physiological or pathological stimulation. Protein synthesis enhancement, which is mediated by the translation of messenger RNAs, is one of the main features of cardiomyocyte hypertrophy. Although the transcriptome shift caused by cardiac hypertrophy induced by different stimuli has been extensively investigated, translatome dynamics in this cellular process has been less studied. Here, we generated a nucleotide-resolution translatome as well as transcriptome data from isolated primary cardiomyocytes undergoing hypertrophy. More than 10,000 open reading frames (ORFs) were detected from the deep sequencing of ribosome-protected fragments (Ribo-seq), which orchestrated the shift of the translatome in hypertrophied cardiomyocytes. Our data suggest that rather than increase the translational rate of ribosomes, the increased efficiency of protein synthesis in cardiomyocyte hypertrophy was attributable to an increased quantity of ribosomes. In addition, more than 100 uncharacterized short ORFs (sORFs) were detected in long noncoding RNA genes from Ribo-seq with potential of micropeptide coding. In a random test of 15 candidates, the coding potential of 11 sORFs was experimentally supported. Three micropeptides were identified to regulate cardiomyocyte hypertrophy by modulating the activities of oxidative phosphorylation, the calcium signaling pathway, and the mitogen-activated protein kinase (MAPK) pathway. Our study provides a genome-wide overview of the translational controls behind cardiomyocyte hypertrophy and demonstrates an unrecognized role of micropeptides in cardiomyocyte biology.

Novel organization of mitochondrial minicircles and guide RNAs in the zoonotic pathogen Trypanosoma lewisi.

Kinetoplastid flagellates are known for several unusual features, one of which is their complex mitochondrial genome, known as kinetoplast (k) DNA, composed of mutually catenated maxi- and minicircles. Trypanosoma lewisi is a member of the Stercorarian group of trypanosomes which is, based on human infections and experimental data, now considered a zoonotic pathogen. By assembling a total of 58 minicircle classes, which fall into two distinct categories, we describe a novel type of kDNA organization in T. lewisi. RNA-seq approaches allowed us to map the details of uridine insertion and deletion editing events upon the kDNA transcriptome. Moreover, sequencing of small RNA molecules enabled the identification of 169 unique guide (g) RNA genes, with two differently organized minicircle categories both encoding essential gRNAs. The unprecedented organization of minicircles and gRNAs in T. lewisi broadens our knowledge of the structure and expression of the mitochondrial genomes of these human and animal pathogens. Finally, a scenario describing the evolution of minicircles is presented.

Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial.

BACKGROUND: Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. METHODS: In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18-60 years with previously untreated, non-keratinising stage III-IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68-70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62-68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30-32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed. FINDINGS: From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9-81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7-80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69-1·39; log-rank p=0·92), with a difference of 0·5% (95% CI -7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (-6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3-4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported. INTERPRETATION: Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma. FUNDING: National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Differential impacts of charcoal-stripped fetal bovine serum on c-Myc among distinct subtypes of breast cancer cell lines.

Charcoal-stripped fetal bovine serum (CS-FBS) is frequently used in studies on hormone-responsive cancers to provide hormone-free cell culture conditions. CS-FBS may influence the growth of cancer cells; however, the underlying mechanisms remain unclear. In this study, we aimed to clarify the effects of CS-FBS on distinct subtypes of breast cancer cells. We found that the crucial oncoprotein c-Myc was significantly inhibited in estrogen receptor alpha (ER-α)-positive breast cancer cells when cultured in CS-FBS-supplemented medium, but it was not suppressed in ER-α-negative cells. The addition of 17ß-estradiol (E2) to CS-FBS-supplemented medium rescued the CS-FBS-induced inhibition of c-Myc, while treatment with 5α-dihydrotestosterone (DHT) suppressed c-Myc expression. Our data demonstrated that CS-FBS may impede the growth of ER-α-positive breast cancer cells via c-Myc inhibition, and this was possibly due to the removal of estrogen. These results highlighted that the core drivers of c-Myc expression were subtype-specific depending on the distinct cell context and special caution should be exercised when using CS-FBS in studies of hormone-responsive cancer cells.

Comparing three induction chemotherapy regimens for patients with locoregionally advanced nasopharyngeal carcinoma based on TNM stage and plasma Epstein-Barr virus DNA level.

BACKGROUND: We compared the efficacy and toxicity of three IC regimens (TPF: taxanes, cisplatin, and 5-fluorouracil; TP: taxanes and cisplatin; and PF: cisplatin and 5-fluorouracil) followed by CCRT in locoregionally advanced NPC. METHODS: The retrospective study involved 1354 patients with newly diagnosed stage III-IVA NPC treated with IC and CCRT. The median follow-up time in our cohort was 50 months. Based on EBV DNA level, all the patients with stage IV were divided into low- (pre-EBV DNA < 1500 copies) and high-risk group (pre-EBV DNA ≥ 1500 copies). Progression free survival (PFS), overall survival (OS), locoregional relapse free survival (LRFS), distant metastasis free survival (DMFS) and grade 3-4 toxicities were compared among different IC regimens. The survival rates were compared using log-rank test and a Cox proportional hazards model was used to perform multivariate analyses. RESULTS: A multivariate analysis revealed TPF to be more effective than TP. Among stage III patients, no significant difference in clinical outcome between the different IC regimens was showed, while TPF was associated with significantly better survival conditions in the stage IV patients. A further subgroup analysis revealed that only patients with pre-EBV DNA ≥ 1500 copies could benefit from the application of TPF among stage IV NPC. In terms of acute toxicities, PF was associated with fewer grade 3/4 acute toxicities. CONCLUSIONS: In low-risk NPC patients, PF-based IC showed similar efficacy as TPF and TP but was associated with fewer grade 3/4 acute toxicities. In high-risk patients, however, the TPF regimen was superior to PF and TP, although grade 3/4 toxicities were more common with the TPF regimen.

dreamBase: DNA modification, RNA regulation and protein binding of expressed pseudogenes in human health and disease.

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.

RMBase v2.0: deciphering the map of RNA modifications from epitranscriptome sequencing data.

More than 100 distinct chemical modifications to RNA have been characterized so far. However, the prevalence, mechanisms and functions of various RNA modifications remain largely unknown. To provide transcriptome-wide landscapes of RNA modifications, we developed the RMBase v2.0 (http://rna.sysu.edu.cn/rmbase/), which is a comprehensive database that integrates epitranscriptome sequencing data for the exploration of post-transcriptional modifications of RNAs and their relationships with miRNA binding events, disease-related single-nucleotide polymorphisms (SNPs) and RNA-binding proteins (RBPs). RMBase v2.0 was expanded with ∼600 datasets and ∼1 397 000 modification sites from 47 studies among 13 species, which represents an approximately 10-fold expansion when compared with the previous release. It contains ∼1 373 000 N6-methyladenosines (m6A), ∼5400 N1-methyladenosines (m1A), ∼9600 pseudouridine (Ψ) modifications, ∼1000 5-methylcytosine (m5C) modifications, ∼5100 2'-O-methylations (2'-O-Me), and ∼2800 modifications of other modification types. Moreover, we built a new module called 'Motif' that provides the visualized logos and position weight matrices (PWMs) of the modification motifs. We also constructed a novel module termed 'modRBP' to study the relationships between RNA modifications and RBPs. Additionally, we developed a novel web-based tool named 'modMetagene' to plot the metagenes of RNA modification along a transcript model. This database will help researchers investigate the potential functions and mechanisms of RNA modifications.

Clinicopathological significance of miR-27b targeting Golgi protein 73 in patients with hepatocellular carcinoma.

Using five bioinformatics analysis software, we identified Golgi protein 73 (GP73) as a putative target of microRNA-27b (miR-27b), which is closely related to various biological processes or diseases such as bone metabolism disease, adipose cell and muscle cell development, pulmonary hypertension, cervical cancer, and breast cancer. However, the clinical significance of miR-27b in hepatocellular carcinoma (HCC) is still unclear. The differential expression of miR-27b in HCC and adjacent normal liver tissues was measured by quantitative reverse transcription PCR. Our results showed that the expression of miR-27b in tumor tissues is lower than that in adjacent nontumor tissues. The expression of miR-27b was significantly lower in HCC tissues with high expression of GP73, when compared with adjacent nontumor tissues. Moreover, down-regulated expression of miR-27b was closely correlated with serum GP73, tumor-node-metastasis stage, tumor size, and portal vein thrombosis. GP73 mRNA might be a target of miR-27b. The 5-year overall survival rate of the low miR-27b expression group was significantly lower than that of the high miR-27b expression group. Moreover, multivariate analysis of prognostic factors, with a Cox proportional hazards model, showed that low miR-27b expression was a significant and independent predictor of poor survival in HCC. Hence, the abnormal expression of miR-27b might be related to the occurrence and development of tumors. Similarly, a study in the Cancer Genome Atlas database demonstrated that the expression of miR-27b in 50 normal individuals was 1.6 times higher than that of 372 patients with liver cancer. The overall survival rate of the low GP73 expression group (275 liver cancer patients) was significantly longer than that of the high GP73 expression group (90 normal individuals). MiR-27b suppresses the expression of GP73 and is therefore a potential prognostic biomarker and therapy target in HCC.

ChIPBase v2.0: decoding transcriptional regulatory networks of non-coding RNAs and protein-coding genes from ChIP-seq data.

The abnormal transcriptional regulation of non-coding RNAs (ncRNAs) and protein-coding genes (PCGs) is contributed to various biological processes and linked with human diseases, but the underlying mechanisms remain elusive. In this study, we developed ChIPBase v2.0 (http://rna.sysu.edu.cn/chipbase/) to explore the transcriptional regulatory networks of ncRNAs and PCGs. ChIPBase v2.0 has been expanded with ∼10 200 curated ChIP-seq datasets, which represent about 20 times expansion when comparing to the previous released version. We identified thousands of binding motif matrices and their binding sites from ChIP-seq data of DNA-binding proteins and predicted millions of transcriptional regulatory relationships between transcription factors (TFs) and genes. We constructed 'Regulator' module to predict hundreds of TFs and histone modifications that were involved in or affected transcription of ncRNAs and PCGs. Moreover, we built a web-based tool, Co-Expression, to explore the co-expression patterns between DNA-binding proteins and various types of genes by integrating the gene expression profiles of ∼10 000 tumor samples and ∼9100 normal tissues and cell lines. ChIPBase also provides a ChIP-Function tool and a genome browser to predict functions of diverse genes and visualize various ChIP-seq data. This study will greatly expand our understanding of the transcriptional regulations of ncRNAs and PCGs.

Exploration on the bioreduction mechanism of Cr(â ¥) by a gram-positive bacterium: Pseudochrobactrum saccharolyticum W1.

Bioremediation of chromium (Cr(Ⅵ)) contaminations has been widely reported, but the research on its removal mechanism is still scarce. Studies on Cr(Ⅵ) removal by strains affiliated to genus Pseudochobactrum revealed the Cr(Ⅵ) efficiency removal through the reduction of Cr(Ⅵ) to Cr(Ⅲ). However, the location of Cr(Ⅵ) reduction reaction and exact mechanism are still unspecified. In this work, a Gram-positive bacterial strain, Pseudochrobactrum saccharolyticum W1 (P. saccharolyticum W1) was isolated and tested to remove approximately 53.7% of Cr(Ⅵ) (initial concentration was 200 mg L-1) from the MSM medium. Analysis of SEM-EDS and TEM-EDS indicated that chromium-containing particles precipitated both on the cell surface and in the cytoplasm. Batch experiments indicated that the heat-treated bacterial cells almost had no ability to remove Cr(Ⅵ) from solution, while the resting cells could remove 62.0% of Cr(Ⅵ) at the initial concentration of 10 mg L-1. Additionally, at this concentration, 64.8% and 70.8% of Cr(Ⅵ) was reduced by cell envelope components and intracellular soluble substances after 6 h, respectively. These results suggested that the removal of Cr(Ⅵ) by P. saccharolyticum W1 was through direct reduction, which occurred on both cell envelop and cytoplasm. The results also showed that cytoplasm was the main site for Cr(Ⅵ) reduction compared to the cell envelop. Further analysis of FTIR and XPS verified that C-H, C-C, CO, C-OH and C-O-C groups of cells involved in correlation with chromium during Cr(Ⅵ) reduction. The study offered an insight into the Cr(VI) reduction mechanism of P. saccharolyticum W1.

A group of tissue-specific microRNAs contribute to the silencing of CUX1 in different cell lineages during development.

Cut-like homeobox 1 (CUX1) is a highly conserved homeoprotein that functions as a transcriptional repressor of genes specifying terminal differentiation. We previously showed that liver-specific microRNA-122 (miR-122) regulates the timing of liver development by silencing CUX1 post-transcriptionally. Since the CUX1 protein is expressed in a subset of embryonic tissues, we hypothesized that it is regulated by specific microRNAs (miRNAs) in each cell type during development. Using a large-scale screening method, we identified ten tissue-specific miRNAs from different cell lineages that directly targeted CUX1. An analysis of the interaction between heart-specific microRNA-208a (miR-208a) and CUX1 in the hearts of developing mouse embryos and in P19CL6 cells undergoing cardiac differentiation indicated that CUX1 is regulated by miR-208a during heart development and cardiomyocyte differentiation. Functional analysis of miR-208a in P19CL6 cells using lentiviral-mediated over-expression showed that it regulates the transition between cellular proliferation and differentiation. These results suggest that these tissue-specific miRNAs might play a common role in timing the progression of terminal differentiation of different cell lineages, possibly by silencing the differentiation repressor CUX1.