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1.
Sci China Life Sci ; 63(4): 501-515, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32170629

RESUMO

RNA can interact with RNA-binding proteins (RBPs), mRNA, or other non-coding RNAs (ncRNAs) to form complex regulatory networks. High-throughput CLIP-seq, degradome-seq, and RNA-RNA interactome sequencing methods represent powerful approaches to identify biologically relevant ncRNA-target and protein-ncRNA interactions. However, assigning ncRNAs to their regulatory target genes or interacting RNA-binding proteins (RBPs) remains technically challenging. Chemical modifications to mRNA also play important roles in regulating gene expression. Investigation of the functional roles of these modifications relies highly on the detection methods used. RNA structure is also critical at nearly every step of the RNA life cycle. In this review, we summarize recent advances and limitations in CLIP technologies and discuss the computational challenges of and bioinformatics tools used for decoding the functions and regulatory networks of ncRNAs. We also summarize methods used to detect RNA modifications and to probe RNA structure.

2.
Mol Cell ; 77(5): 999-1013.e6, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32017896

RESUMO

U6 snRNA, as an essential component of the catalytic core of the pre-mRNA processing spliceosome, is heavily modified post-transcriptionally, with 2'-O-methylation being most common. The role of these modifications in pre-mRNA splicing as well as their physiological function in mammals have remained largely unclear. Here we report that the La-related protein LARP7 functions as a critical cofactor for 2'-O-methylation of U6 in mouse male germ cells. Mechanistically, LARP7 promotes U6 loading onto box C/D snoRNP, facilitating U6 2'-O-methylation by box C/D snoRNP. Importantly, ablation of LARP7 in the male germline causes defective U6 2'-O-methylation, massive alterations in pre-mRNA splicing, and spermatogenic failure in mice, which can be rescued by ectopic expression of wild-type LARP7 but not an U6-loading-deficient mutant LARP7. Our data uncover a novel role of LARP7 in regulating U6 2'-O-methylation and demonstrate the functional requirement of such modification for splicing fidelity and spermatogenesis in mice.

3.
Chin Med J (Engl) ; 133(2): 212-220, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31929369

RESUMO

BACKGROUND: Recent evidence has shown that prophylactic antibiotic treatment in patients with acute pancreatitis is not associated with a significant decrease in mortality or morbidity. The use and efficacy of prophylactic antibiotic treatment in acute pancreatitis remain controversial. This meta-analysis was conducted to assess whether antibiotic prophylaxis is beneficial in patients with acute pancreatitis. METHODS: We searched randomized controlled trials (RCTs) of prophylactic use of antibiotics using Medline (PubMed), Embase, the Cochrane Library, and Web of Science. The data were analyzed using Review Manager 5.3 software. We performed pooled analyses for infected pancreatic necrosis, mortality, surgical intervention, and non-pancreatic infection. Odds ratios (ORs) from each trial were pooled using a random or fixed effects model, depending on the heterogeneity of the included studies. Sub-group analysis or sensitivity analysis was conducted to explore potential sources of heterogeneity, when necessary. RESULTS: Totally, 11 RCTs involving 747 participants were included, with an intervention group (prophylactic use of antibiotics, n = 376) and control group (n = 371). No significant differences were found regarding antibiotic prophylaxis with respect to incidence of infected pancreatic necrosis (OR, 0.74; 95% confidence interval [CI], 0.50-1.09; P = 0.13), surgical intervention (OR, 0.92; 95% CI, 0.62-1.38; P = 0.70), and morality (OR, 0.71; 95% CI, 0.44-1.15; P = 0.16). However, antibiotic prophylaxis was associated with a statistically significant reduction in the incidence of non-pancreatic infection (OR, 0.59; 95% CI, 0.42-0.84; P = 0.004). CONCLUSIONS: Prophylactic antibiotics can reduce the incidence of non-pancreatic infection in patients with AP.

4.
Onco Targets Ther ; 12: 6191-6201, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496724

RESUMO

Background: The Wilms' tumor suppressor WT1 is reported to work in a range of physiological processes at both transcriptional and posttranscriptional level. WT1-associating protein (WTAP), a nuclear protein co-localized with splicing factors, also plays a vital role in cellular function and cancer progression. However, little is known about the role of WTAP in ovarian cancer and the underlying mechanism. Materials and methods: To evaluate the expression of WTAP, multiple means were applied in clinical tissues, including immunohistochemistry, quantitative reverse transcriptase PCR (qRT-PCR), and Western blot. Two representative ovarian cancer cell lines (3AO and SKOV3) were used to assess the malignant influence of WTAP on proliferation, apoptosis, and migration. To explore its function, WTAP was additionally down-regulated by lentivirus. Results: High expression of WTAP in high-grade serous ovarian carcinoma (HGSOC) predicted a shorter overall survival (P<0.01). Furthermore, WTAP expression was higher in HGSOC, compared with that in normal ovary group (P<0.01), benign ovarian tumor group (P<0.01), and non-HGSOC group (P<0.05). In HGSOC, high expression of WTAP was significantly related with the lymph node metastasis (P<0.05). In ovarian cancer cell lines, cell proliferation and migration were considerably reduced after WTAP was down-regulated, while apoptotic rate was increased. Moreover, the effect of WTAP in 3AO and SKOV3 might be relevant with MAPK and AKT signaling pathways. Conclusion: WTAP is highly expressed in HGSOC, and indicates a worse survival outcome. Therefore, it is highly possible that WTAP has a prognostic implication in the patients of HGSOC. In addition, WTAP down-regulation also plays a tumor suppressor role in 3AO and SKOV3 cell lines.

5.
Medicine (Baltimore) ; 98(20): e15710, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096520

RESUMO

BACKGROUND: To systematically evaluate efficacy of traditional Chinese medicine (TCM) in treating chronic gastritis (CG). METHODS: Data sources from PubMed, Embase, Springer Link, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Chinese Biomedicine Database, and Wan-fang database were searched up to July 5, 2018. Review Manager software version 5.3, the Cochrane Collaboration's risk of bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation profiler software were conducted for this meta-analysis. RESULTS: Sixteen studies involving 1673 participants (906 vs 767) were included in this study. Pooled data showed significant statistical differences between TCM groups and current routine pharmacotherapy (RP) groups in overall clinical efficacy (odds ratio [OR] 4.65; 95% confidence interval [CI] 3.29, 6.56; P < .00001), efficacy under endoscopy (OR 2.46; 95% CI 1.12, 5.43; P = .03), stomach distension (mean difference [MD] -0.37; 95% CI -0.56, -0.19; P < .0001), stomachache (standardized MD [SMD] -0.80; 95% CI -1.45, -0.14; P = .02), and belching (SMD -2.00; 95% CI -3.80, -0.20; P = .03). However, acid regurgitation (SMD -0.71; 95% CI -1.69, 0.28; P = .16) and anorexia (SMD -0.75; 95% CI -2.30, 0.80; P = .35) showed no significant statistical differences between 2 groups. In addition, incidence of adverse reactions of TCM groups was lower than that of RP groups. CONCLUSION: Evidence from this meta-analysis suggests that TCM could be more efficacious than current RP in treating CG. But further standardized research of rigorous design should be needed to further validate its efficacy.


Assuntos
Mucosa Gástrica/efeitos dos fármacos , Gastrite/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Doença Crônica , Endoscopia do Sistema Digestório/métodos , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/patologia , Gastrite/diagnóstico por imagem , Gastrite/patologia , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
6.
Medicine (Baltimore) ; 98(17): e15308, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31027096

RESUMO

This retrospective study investigated the effectiveness and safety of acupuncture as an adjunctive therapy to topical ibuprofen (TIP) for patients with chronic knee pain (CKP) due to osteoarthritis.This retrospective study analyzed medical records of 84 patients with CKP due to osteoarthritis. These patients were divided into a treatment group (n = 42) and a control group (n = 42). The patients in the treatment group were treated with acupuncture plus TIP, while the subjects in the control group received TIP monotherapy. The primary effectiveness endpoint was assessed by Western Ontario and McMaster Universities osteoarthritis index (WOMAC). The secondary effectiveness endpoints were evaluated by the numeric rating scale (NRS), 12-item Short FormHealth Survey (SF-12, mainly including mental component summary [MCS], and physical component summary [PCS]), and adverse events. All patients received an 8-week treatment. All endpoints were measured pre-treatment and posttreatment.The patients who received acupuncture plus TIP showed better effectiveness in both primary endpoint of WOMAC scale (pain, P < .01; function, P < .01; and stiffness, P < .01) and secondary endpoints of NRS (P < .01), and SF-12 (MCS, P < .01; and PCS, P < .01), than patients who received TIP monotherapy. In addition, both groups had similar safety profile.The results of this study showed that the effectiveness of acupuncture plus TIP may be better than TIP monotherapy for patients with CKP due to osteoarthritis.


Assuntos
Terapia por Acupuntura/métodos , Ibuprofeno/uso terapêutico , Osteoartrite do Joelho/terapia , Manejo da Dor/métodos , Administração Cutânea , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Terapia Combinada , Feminino , Humanos , Ibuprofeno/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Medicine (Baltimore) ; 98(8): e14589, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813181

RESUMO

This retrospective study investigated the efficacy and safety of extracorporeal shock wave (EPSW) combined with hyaluronic acid (HA) for patients with knee osteoarthritis (KOA).This retrospective study included 70 patients with KOA. Of those subjects, 35 of them received EPSW combined HA, and were allocated to a treatment group, while the other 35 participants received HA alone and were allocated to a control group. Patients in both groups were treated for a total of 8 weeks. The primary outcome was measured by visual analog scale (VAS). The secondary outcomes were measured by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and knee injury and osteoarthritis outcome score (KOOS). In addition, adverse events (AEs) were also evaluated. All outcomes were measured before and after the treatment.After the treatment, patients in the treatment group exhibited better efficacy in VAS (P < .01), WOMAC scale (pain, P < .01; function, P < .01; and stiffness, P < .01), and KOOS scores (pain, P < .01; function in daily living, P < .01; symptoms, P < .01; sport and recreation, P < .01; and quality of life, P < .01), than patients in the control group. In addition, no significant differences regarding the AEs were found between 2 groups.The findings of this study demonstrated that the efficacy of EPSW combined with HA is superior to the HA alone for patients with KOA.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas/métodos , Ácido Hialurônico/administração & dosagem , Osteoartrite do Joelho/terapia , Viscossuplementos/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Tratamento por Ondas de Choque Extracorpóreas/efeitos adversos , Feminino , Humanos , Ácido Hialurônico/efeitos adversos , Injeções Intra-Articulares , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Viscossuplementos/efeitos adversos
8.
Elife ; 82019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30735121

RESUMO

MicroRNA-122 (miR-122) is the most abundant microRNA in hepatocytes and a central player in liver biology and disease. Herein, we report a previously unknown role for miR-122 in hepatocyte intrinsic innate immunity. Restoration of miR-122 levels in hepatoma cells markedly enhanced the activation of interferons (IFNs) in response to a variety of viral nucleic acids or simulations, especially in response to hepatitis C virus RNA and poly (I:C). Mechanistically, miR-122 downregulated the phosphorylation (Tyr705) of STAT3, thereby removing the negative regulation of STAT3 on IFN-signaling. STAT3 represses IFN expression by inhibiting interferon regulatory factor 1 (IRF1), whereas miR-122 targets MERTK, FGFR1 and IGF1R, three receptor tyrosine kinases (RTKs) that directly promote STAT3 phosphorylation. This work identifies a miR-122-RTKs/STAT3-IRF1-IFNs regulatory circuitry, which may play a pivotal role in regulating hepatocyte innate immunity. These findings renewed our knowledge of miR-122's function and have important implications for the treatment of hepatitis viruses.

9.
J Trauma Acute Care Surg ; 86(3): 440-447, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30489503

RESUMO

BACKGROUND: Genetic backgrounds have been recognized as significant determinants of susceptibility to sepsis. CXC chemokines play a significant role in innate immunity against infectious diseases. Genetic polymorphisms of CXC chemokine genes have been widely studied in inflammatory and infectious diseases but not in sepsis. Thus, we aimed to investigate the clinical relevance of CXC chemokine gene polymorphisms and susceptibility to sepsis in a traumatically injured population. METHODS: Thirteen tag single nucleotide polymorphisms were selected from CXC chemokine genes using a multimarker tagging algorithm in the Tagger software. Three independent cohorts of injured patients (n = 1700) were prospectively recruited. Selected single nucleotide polymorphisms were genotyped using an improved multiplex ligation detection reaction method. Cytokine production in lipopolysaccharide-stimulated whole blood was measured using an enzyme-linked immunosorbent assay. RESULTS: Among the 13 tag single nucleotide polymorphisms, four single nucleotide polymorphisms (rs1429638, rs266087, rs2297630, and rs2839693) were significantly associated with the susceptibility to sepsis, and three (rs3117604, rs1429638, and rs4074) were significantly associated with an increased multiple organ dysfunction score in the derivation cohort. However, only the clinical relevance of rs1429638 and rs266087 was confirmed in the validation cohorts. In addition, rs2297630 was significantly associated with interleukin 6 production. CONCLUSION: The rs1429638 polymorphism in the CXCL1 gene and the rs2297630 polymorphism in the CXCL12 gene were associated with altered susceptibility to sepsis and might be used as important genetic markers to assess the risks of sepsis in trauma patients. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level II.

10.
Methods Mol Biol ; 1870: 107-124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30539550

RESUMO

Over 100 types of chemical modifications have been identified in protein-coding and noncoding RNAs (ncRNAs). However, the prevalence, regulation, and function of diverse RNA modifications remain largely unknown. In this chapter, we describe how to annotate, visualize, and analyze the RNA modification sites from the high-throughput epitranscriptome sequencing data using RMBase platform and software. We developed two stand-alone computational software, modAnnotator and metaProfile, to annotate and visualize RNA modification sites and their prevalence in the gene body. In addition, we constructed interactive web implementations to decode the atlas of various RNA modifications, including the N6-methyladenosine (m6A) modification, pseudouridine (Ψ) modification, 5-methylcytosine (m5C) modification, and 2'-O-methylation (2'-O-Me) modification, as well as other types of modifications. We also developed web-based interfaces to analyze the associations between RNA modification sites with miRNA target sites and disease-related single-nucleotide polymorphisms (SNPs). Moreover, RMBase provides a genome browser and a web-based modTool to query, annotate, and visualize various RNA modifications. RMBase is expected to provide comprehensive interfaces and tools to facilitate the analysis and functional study of the massive RNA modification sites. The software and platform are available at http://rna.sysu.edu.cn/rmbase/modSoftware.php .


Assuntos
Biologia Computacional/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Processamento Pós-Transcricional do RNA , Transcriptoma , 5-Metilcitosina , Adenosina/análogos & derivados , Sítios de Ligação , Bases de Dados de Ácidos Nucleicos , Humanos , Metilação , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Software , Interface Usuário-Computador , Navegador
11.
Mol Oncol ; 12(11): 1949-1964, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30171794

RESUMO

miR-372/373, a cluster of stem cell-specific microRNAs transactivated by the Wnt pathway, has been reported to be dysregulated in various cancers, particularly colorectal cancer (CRC); however, the unique role of these microRNAs in cancer remains to be discovered. In the present study, we characterized the upregulation in expression of miR-372/373 in CRC tissues from The Cancer Genome Atlas data, and then showed that overexpression of miR-372/373 enhanced the stemness of CRC cells by enriching the CD26/CD24-positive cell population and promoting self-renewal, chemotherapy resistance and the invasive potential of CRC cells. To clarify the mechanism underlying microRNA-induced stemness, we profiled 45 cell signaling pathways in CRC cells overexpressing miR-372/373 and found that stemness-related pathways, such as Nanog and Hedgehog, were upregulated. Instead, differentiation-related pathways, such as NFκB, MAPK/Erk and VDR, were markedly repressed by miR-372/373. Numerous new targets of miR-372/373 were identified, including SPOP, VDR and SETD7, all of which are factors important for cell differentiation. Furthermore, in contrast to the increase in miR-372/373 expression in CRC tissues, the expression levels of SPOP and VDR mRNA were significantly downregulated in these tissues, indicative of the poor differentiation status of CRC. Taken together, our findings suggest that miR-372/373 enhance CRC cell stemness by repressing the expression of differentiation genes. These results provide new insights for understanding the function and mechanisms of stem cell-specific microRNAs in the development of metastasis and drug resistance in CRC.


Assuntos
Neoplasias Colorretais/metabolismo , Sistema de Sinalização das MAP Quinases , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , RNA Neoplásico/metabolismo , Animais , Células CACO-2 , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/patologia , RNA Neoplásico/genética
12.
Eur Urol ; 74(6): 756-763, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30143382

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) can be used as prognostic biomarkers in many types of cancer. OBJECTIVE: We sought to establish an lncRNA signature to improve postoperative risk stratification for patients with localized clear cell renal cell carcinoma (ccRCC). DESIGN, SETTING, AND PARTICIPANTS: Based on the RNA-seq data of 444 stage I-III ccRCC tumours from The Cancer Genome Atlas project, we built a four-lncRNA-based classifier using the least absolute shrinkage and selection operation (LASSO) Cox regression model in 222 randomly selected samples (training set) and validated the classifier in the remaining 222 samples (internal validation set). We confirmed this classifier in an external validation set of 88 patients with stage I-III ccRCC from a Japan cohort and using quantitative reverse transcription polymerase chain reaction (RT-PCR) in another three independent sets that included 1869 patients from China with stage I-III ccRCC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox regression, Harrell's concordance index (c-index), and time-dependent receiver operating characteristic curves were used to evaluate the association of the classifier with overall survival, disease-specific survival, and disease-free survival. RESULTS AND LIMITATIONS: Using the LASSO Cox regression model, we built a classifier named RCClnc4 based on four lncRNAs: ENSG00000255774, ENSG00000248323, ENSG00000260911, and ENSG00000231666. In the RNA-seq and RT-PCR data sets, the RCClnc4 signature significantly stratified patients into high-risk versus low-risk groups in terms of clinical outcome across and within subpopulations and remained as an independent prognostic factor in multivariate analyses (hazard ratio range, 1.34 [95% confidence interval {CI}: 1.03-1.75; p=0.028] to 1.89 [95% CI, 1.55-2.31; p<0.001]) after adjusting for clinical and pathologic factors. The RCClnc4 signature achieved a higher accuracy (mean c-index, 0.72) than clinical staging systems such as TNM (mean c-index, 0.62) and the stage, size, grade, and necrosis (SSIGN) score (mean c-index, 0.64), currently reported prognostic signatures and biomarkers for the estimation of survival. When integrated with clinical characteristics, the composite clinical and lncRNA signature showed improved prognostic accuracy in all data sets (TNM + RCClnc4 mean c-index, 0.75; SSIGN + RCClnc4 score mean c-index, 0.75). The RCClnc4 classifier was able to identify a clinically significant number of both high-risk stage I and low-risk stage II-III patients. CONCLUSIONS: The RCClnc4 classifier is a promising and potential prognostic tool in predicting the survival of patients with stage I-III ccRCC. Combining the lncRNA classifier with clinical and pathological parameters allows for accurate risk assessment in guiding clinical management. PATIENT SUMMARY: The RCClnc4 classifier could facilitate patient management and treatment decisions.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Renais/genética , RNA Longo não Codificante/genética , Transcriptoma , Adulto , Idoso , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , China/epidemiologia , Intervalo Livre de Doença , Feminino , Predisposição Genética para Doença , Humanos , Japão/epidemiologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
13.
Medicine (Baltimore) ; 97(28): e11270, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29995759

RESUMO

This retrospective study investigated the effect of knee joint function training (KJFT) on joint functional rehabilitation after knee replacement in Chinese patients with severe knee osteoarthritis (KOA).Eighty-six eligible patients with severe KOA were included. Of those, 43 patients in the intervention group received KJFT and educational program, while the other 43 patients received educational program only. Primary outcome was measured by the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Secondary outcomes were measured by the visual analogue scale (VAS), and Knee Injury and Osteoarthritis Outcome Score (KOOS). All outcomes were assessed at baseline, 1 week before and 3 months after the surgery.Patients in the intervention group showed encouraging benefit neither at 1 week before nor 3 months after the surgery in all outcome measurements, including WOMAC, VAS, and KOOS, when compared with the patients in the control group.The results of this study did not show promising effect of KJFT for joint functional rehabilitation in Chinese patients with KOA after KJR.


Assuntos
Artroplastia do Joelho , Terapia por Exercício/métodos , Articulação do Joelho/fisiopatologia , Osteoartrite do Joelho/cirurgia , Dor Pós-Operatória , Qualidade de Vida , Idoso , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Artroplastia do Joelho/reabilitação , Feminino , Humanos , Masculino , Medição da Dor/métodos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/terapia , Educação de Pacientes como Assunto , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Resultado do Tratamento
14.
Huan Jing Ke Xue ; 39(4): 1833-1839, 2018 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965010

RESUMO

Anaerobic ammonium oxidation coupled to iron (Ⅲ) reduction (termed Feammox) is a recently discovered pathway of nitrogen cycling. However, little is known about the pathways of N transformation via the Feammox process in riparian zones. In this study, evidence of Feammox in the riparian zone soil layers (0-20 cm) was demonstrated using the isotope tracing technique and a high-throughput sequencing technology. The results showed that Feammox occurred in the riparian zones in four different soil layers (A:0-5 cm, B:5-10 cm, C:10-15 cm, D:15-20 cm) and the Feammox rates ranged from 0.25 mg·(kg·d)-1 to 0.29 mg·(kg·d)-1. In the B soil sample, the Feammox rate was significantly higher than in the other soil samples (P<0.05). In addition, iron reducing bacteria played an essential role in the Feammox process, and Anaeromyxobacter and Geobacter were detected in all the soil samples. In the B soil sample, the abundance of iron reducing bacteria was significantly higher than in the other soil samples (P<0.05). Overall, the co-occurrence of ammonium oxidation and iron reduction suggest that Feammox can play an essential role in the pathway of nitrogen removal in riparian zones.


Assuntos
Ciclo do Nitrogênio , Microbiologia do Solo , Solo/química , Compostos de Amônio , Bactérias/classificação , Bactérias/metabolismo , Nitrogênio
15.
Org Lett ; 20(4): 1050-1053, 2018 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-29400477

RESUMO

Asymmetric synthesis of the pentacyclic alkaloid (-)-cephalotaxine was accomplished via palladium-catalyzed enantioselective Tsuji allylation for construction of the aza-containing tetrasubstituted stereogenic center (95% yield, 93% ee). The allyl enol carbonate precursor was prepared from Hanaoka's ketone intermediate, which was formed by a novel formic acid promoted ring-expansion reaction.

16.
Cell Death Differ ; 25(9): 1581-1597, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29449644

RESUMO

Skeletal muscle differentiation is controlled by multiple cell signaling pathways, however, the JNK/MAPK signaling pathway dominating this process has not been fully elucidated. Here, we report that the JNK/MAPK pathway was significantly downregulated in the late stages of myogenesis, and in contrast to P38/MAPK pathway, it negatively regulated skeletal muscle differentiation. Based on the PAR-CLIP-seq analysis, we identified six elevated miRNAs (miR-1a-3p, miR-133a-3p, miR-133b-3p, miR-206-3p, miR-128-3p, miR-351-5p), namely myogenesis-associated miRNAs (mamiRs), negatively controlled the JNK/MAPK pathway by repressing multiple factors for the phosphorylation of the JNK/MAPK pathway, including MEKK1, MEKK2, MKK7, and c-Jun but not JNK protein itself, and as a result, expression of transcriptional factor MyoD and mamiRs were further promoted. Our study revealed a novel double-negative feedback regulatory pattern of cell-specific miRNAs by targeting phosphorylation kinase signaling cascade responsible for skeletal muscle development.


Assuntos
Sistema de Sinalização das MAP Quinases , MicroRNAs/metabolismo , Desenvolvimento Muscular/genética , Animais , Antagomirs/metabolismo , Proteínas Argonauta/metabolismo , Diferenciação Celular , Linhagem Celular , Regulação para Baixo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Proteína MyoD/metabolismo , Fosforilação , Mapas de Interação de Proteínas , Ratos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Methods Mol Biol ; 1724: 193-207, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29322451

RESUMO

Circular RNAs (circRNAs) represent an abundant group of noncoding RNAs in eukaryotes and are emerging as important regulatory molecules in physiological and pathological processes. However, the precise mechanisms and functions of most of circRNAs remain largely unknown. In this chapter, we describe how to identify circRNA-microRNA interactions from Argonaute (AGO) cross-linking and immunoprecipitation followed by sequencing (CLIP-Seq) and RNA-Seq data using starBase platform and software. We developed three stand-alone computational software, including circSeeker, circAnno, and clipSearch, to identify and annotate circRNAs and their interactions with microRNAs (miRNAs). In addition, we developed interactive Web applications to evaluate circRNA-miRNA interactions identified from CLIP-Seq data and discover the miRNA-sponge circRNAs. starBase platform provides a genome browser to comparatively analyze these interactions at multiple levels. As a means of comprehensively integrating CLIP-Seq and RNA-Seq data, starBase platform is expected to reveal the regulatory networks involving miRNAs and circRNAs. The software and platform are available at http://starbase.sysu.edu.cn/circTools.php.


Assuntos
Reagentes para Ligações Cruzadas/metabolismo , Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Imunoprecipitação/métodos , MicroRNAs/metabolismo , RNA/genética , Análise de Sequência de RNA/métodos , Proteínas Argonauta/metabolismo , Biologia Computacional , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , Software
18.
ACS Appl Mater Interfaces ; 10(11): 9645-9652, 2018 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-29309121

RESUMO

Direct reduction of metal oxides into a few transition metal dichalcogenide (TMDCs) monolayers has been recently explored as an alternative method for large area and uniform deposition. However, not many studies have addressed the characteristics and requirement of the metal oxides into TMDCs by the selenization/sulfurization processes, yielding a wide range of outstanding properties to poor electrical characteristics with nonuniform films. The large difference implies that the process is yet not fully understood. In particular, the selenization/sulfurization at low temperature leads to poor crystallinity films with poor electrical performance, hindering its practical development. A common approach to improve the quality of the selenized/sulfurized films is by further increasing the process temperature, thus requiring additional transfer in order to explore the electrical properties. Here, we show that by finely tuning the quality of the predeposited oxide the selenization/sulfurization temperature can be largely decreased, avoiding major substrate damage and allowing direct device fabrication. The direct relationship between the role of selecting different metal oxides prepared by e-beam evaporation and reactive sputtering and their oxygen deficiency/vacancy leading to quality influence of TMDCs was investigated in detail. Because of its outstanding physical properties, the formation of tungsten diselenide (WSe2) from the reduction of tungsten oxide (WO x) was chosen as a model for proof of concept. By optimizing the process parameters and the selection of metal oxides, layered WSe2 films with controlled atomic thickness can be demonstrated. Interestingly, the domain size and electrical properties of the layered WSe2 films are highly affected by the quality of the metal oxides, for which the layered WSe2 film with small domains exhibits a metallic behavior and the layered WSe2 films with larger domains provides clear semiconducting behavior. Finally, an 8'' wafer scale-layered WSe2 film was demonstrated, giving a step forward in the development of 2D TMDC electronics in the industry.

19.
Cell Rep ; 22(1): 286-298, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29298429

RESUMO

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.


Assuntos
Neoplasias Colorretais , Bases de Dados Genéticas , Genômica , Neoplasias Hepáticas , Proteínas de Neoplasias , Proteínas de Ligação a RNA , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Variações do Número de Cópias de DNA , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
20.
Nucleic Acids Res ; 46(D1): D85-D91, 2018 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-29059382

RESUMO

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.


Assuntos
Bases de Dados Genéticas , Pseudogenes , DNA/genética , DNA/metabolismo , Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Ligação Proteica/genética , RNA/genética , RNA/metabolismo , Processamento Pós-Transcricional do RNA , Proteínas de Ligação a RNA/metabolismo , Análise de Sequência de RNA
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