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1.
Cell ; 182(1): 245-261.e17, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32649877

RESUMO

Genomic studies of lung adenocarcinoma (LUAD) have advanced our understanding of the disease's biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD remain poorly understood. We carried out a comprehensive proteomics analysis of 103 cases of LUAD in Chinese patients. Integrative analysis of proteome, phosphoproteome, transcriptome, and whole-exome sequencing data revealed cancer-associated characteristics, such as tumor-associated protein variants, distinct proteomics features, and clinical outcomes in patients at an early stage or with EGFR and TP53 mutations. Proteome-based stratification of LUAD revealed three subtypes (S-I, S-II, and S-III) related to different clinical and molecular features. Further, we nominated potential drug targets and validated the plasma protein level of HSP 90ß as a potential prognostic biomarker for LUAD in an independent cohort. Our integrative proteomics analysis enables a more comprehensive understanding of the molecular landscape of LUAD and offers an opportunity for more precise diagnosis and treatment.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Proteômica , Adenocarcinoma de Pulmão/genética , Povo Asiático/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Sistemas de Liberação de Medicamentos , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação/genética , Estadiamento de Neoplasias , Fosfoproteínas/metabolismo , Análise de Componente Principal , Prognóstico , Proteoma/metabolismo , Resultado do Tratamento , Proteína Supressora de Tumor p53/genética
2.
BMC Genomics ; 25(1): 373, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627659

RESUMO

The common dolphin (Delphinus delphis) is widely distributed worldwide and well adapted to various habitats. Animal genomes store clues about their pasts, and can reveal the genes underlying their evolutionary success. Here, we report the first high-quality chromosome-level genome of D. delphis. The assembled genome size was 2.56 Gb with a contig N50 of 63.85 Mb. Phylogenetically, D. delphis was close to Tursiops truncatus and T. aduncus. The genome of D. delphis exhibited 428 expanded and 1,885 contracted gene families, and 120 genes were identified as positively selected. The expansion of the HSP70 gene family suggested that D. delphis has a powerful system for buffering stress, which might be associated with its broad adaptability, longevity, and detoxification capacity. The expanded IFN-α and IFN-ω gene families, as well as the positively selected genes encoding tripartite motif-containing protein 25, peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, and p38 MAP kinase, were all involved in pathways for antiviral, anti-inflammatory, and antineoplastic mechanisms. The genome data also revealed dramatic fluctuations in the effective population size during the Pleistocene. Overall, the high-quality genome assembly and annotation represent significant molecular resources for ecological and evolutionary studies of Delphinus and help support their sustainable treatment and conservation.


Assuntos
Golfinhos Comuns , Animais , Evolução Biológica , Cromossomos/genética , Imunidade Inata/genética , Filogenia
3.
Small ; 20(29): e2310825, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38342581

RESUMO

Bifunctional electrocatalysts with excellent activity and durability are highly desirable for alkaline overall water splitting, yet remain a significant challenge. In this contribution, palm-like Mo5N6/Ni3S2 heterojunction arrays anchored in conductive Ni foam (denoted as Mo5N6-Ni3S2 HNPs/NF) are developed. Benefiting from the optimized electronic structure configuration, hierarchical branched structure and abundant heterogeneous interfaces, the as-synthesized Mo5N6-Ni3S2 HNPs/NF electrode exhibits remarkably stable bifunctional electrocatalytic activity in 1 m KOH solution. It only requires ultralow overpotentials of 59 and 190 mV to deliver a current density of 10 mA cm-2 for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in 1 m KOH solution, respectively. Importantly, the overall water splitting electrolyzer assembled by Mo5N6-Ni3S2 HNPs/NF exhibits an exceptionally low cell voltage (1.48 V@10 mA cm-2) and outstanding durability, surpassing most of the reported Ni-based bifunctional materials. Density functional theory (DFT) further confirms the heterostructure can optimize the Gibbs free energies of H and O-containing intermediates (OH, O, OOH) during HER and OER processes, thereby accelerating the catalytic kinetics of electrochemical water splitting. The findings provide a new design strategy toward low-cost and excellent catalysts for overall water splitting.

4.
Toxicol Appl Pharmacol ; 484: 116840, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307258

RESUMO

Isoprenaline hydrochloride (IH) is a ß-adrenergic receptor agonist commonly used in the treatment of hypotension, shock, asthma, and other diseases. However, IH-induced cardiotoxicity limits its application. A large number of studies have shown that long noncoding RNA (lncRNA) regulates the occurrence and development of cardiovascular diseases. This study aimed to investigate whether abnormal lncRNA expression is involved in IH-mediated cardiotoxicity. First, the Sprague-Dawley (SD) rat myocardial injury model was established. Circulating exosomes were extracted from the plasma of rats and identified. In total, 108 differentially expressed (DE) lncRNAs and 150 DE mRNAs were identified by sequencing. These results indicate that these lncRNAs and mRNAs are substantially involved in chemical cardiotoxicity. Further signaling pathway and functional studies indicated that lncRNAs and mRNAs regulate several biological processes, such as selective mRNA splicing through spliceosomes, participate in sphingolipid metabolic pathways, and play a certain role in the circulatory system. Finally, we obtained 3 upregulated lncRNAs through reverse transcription-quantitative PCR (RT-qPCR) verification and selected target lncRNA-mRNA pairs according to the regulatory relationship of lncRNA/mRNA, some of which were associated with myocardial injury. This study provides valuable insights into the role of lncRNAs as novel biomarkers of chemical-induced cardiotoxicity.


Assuntos
Exossomos , RNA Longo não Codificante , Ratos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Isoproterenol/toxicidade , Redes Reguladoras de Genes , Ratos Sprague-Dawley , Cardiotoxicidade , Exossomos/genética , Exossomos/metabolismo , RNA Mensageiro/metabolismo
5.
Artigo em Inglês | MEDLINE | ID: mdl-38662093

RESUMO

Ketamine has demonstrated rapid and sustained antidepressant effects, marking its emergence as an innovative treatment of depression. Despite the growing number of preclinical and clinical studies exploring the antidepressant effects of ketamine and its enantiomers, a comprehensive bibliometric analysis in this field has yet to be conducted. This study employs bibliometric methods and visualization tools to examine the literature and identify key topics related to the antidepressant effects of ketamine and its enantiomers. We sourced publications on the antidepressant effects of ketamine and its enantiomers from the Web of Science Core Collection (WOSCC) database, covering the period from 2000 to 2023. Tools such as VOSviewer, CiteSpace and the R package "bibliometrix" were utilized for visual analysis. The study included 4,274 publications, with a notable increase in publications peaking in 2022. Co-occurrence analysis highlighted two primary research focal points: the efficacy and safety of ketamine and its enantiomers in treating depression, and the mechanisms behind their antidepressant effects. In conclusion, this analysis revealed a significant increase in research on the antidepressant effects of ketamine and its enantiomers over the past two decades, leading to the approval of esketamine nasal spray for treatment-resistant depression. The rapid antidepressant effects of ketamine have spurred further studies into its mechanisms of action and the search for new antidepressants with fewer side effects.

6.
Proc Natl Acad Sci U S A ; 118(37)2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34503999

RESUMO

The ancestors of marine mammals once roamed the land and independently committed to an aquatic lifestyle. These macroevolutionary transitions have intrigued scientists for centuries. Here, we generated high-quality genome assemblies of 17 marine mammals (11 cetaceans and six pinnipeds), including eight assemblies at the chromosome level. Incorporating previously published data, we reconstructed the marine mammal phylogeny and population histories and identified numerous idiosyncratic and convergent genomic variations that possibly contributed to the transition from land to water in marine mammal lineages. Genes associated with the formation of blubber (NFIA), vascular development (SEMA3E), and heat production by brown adipose tissue (UCP1) had unique changes that may contribute to marine mammal thermoregulation. We also observed many lineage-specific changes in the marine mammals, including genes associated with deep diving and navigation. Our study advances understanding of the timing, pattern, and molecular changes associated with the evolution of mammalian lineages adapting to aquatic life.


Assuntos
Adaptação Fisiológica , Evolução Molecular , Genoma , Genômica , Mamíferos/fisiologia , Filogenia , Termogênese/genética , Animais , Fatores de Transcrição NFI/genética , Fatores de Transcrição NFI/metabolismo , Seleção Genética , Semaforinas/genética , Semaforinas/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
7.
J Virol ; 96(14): e0073822, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35762755

RESUMO

Respiratory coronaviruses cause serious health threats to humans and animals. Porcine respiratory coronavirus (PRCoV), a natural transmissible gastroenteritis virus (TGEV) mutant with partial spike deletion, causes mild respiratory disease and is an interesting animal respiratory coronavirus model for human respiratory coronaviruses. However, the absence of robust ex vivo models of porcine airway epithelium hinders an understanding of the pathogenesis of PRCoV infection. Here, we generated long-term porcine airway organoids (AOs) derived from basal epithelial cells, which recapitulate the in vivo airway complicated epithelial cellularity. Both 3D and 2D AOs are permissive for PRCoV infection. Unlike TGEV, which established successful infection in both AOs and intestinal organoids, PRCoV was strongly amplified only in AOs, not intestinal organoids. Furthermore, PRCoV infection in AOs mounted vigorous early type I and III interferon (IFN) responses and upregulated the expression of overzealous inflammatory genes, including pattern recognition receptors (PRRs) and proinflammatory cytokines. Collectively, these data demonstrate that stem-derived porcine AOs can serve as a promising disease model for PRCoV infection and provide a valuable tool to study porcine respiratory infection. IMPORTANCE Porcine respiratory CoV (PRCoV), a natural mutant of TGEV, shows striking pathogenetic similarities to human respiratory CoV infection and provides an interesting animal model for human respiratory CoVs, including SARS-CoV-2. The lack of an in vitro model recapitulating the complicated cellularity and structure of the porcine respiratory tract is a major roadblock for the study of PRCoV infection. Here, we developed long-term 3D airway organoids (AOs) and further established 2D AO monolayer cultures. The resultant 3D and 2D AOs are permissive for PRCoV infection. Notably, PRCoV mediated pronounced IFN and inflammatory responses in AOs, which recapitulated the inflammatory responses associated with PRCoV in vivo infection. Therefore, porcine AOs can be utilized to characterize the pathogenesis of PRCoV and, more broadly, can serve as a universal platform for porcine respiratory infection.


Assuntos
Imunidade Inata , Organoides , Coronavirus Respiratório Porcino , Sistema Respiratório , Animais , COVID-19 , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Modelos Animais de Doenças , Humanos , Organoides/imunologia , Organoides/virologia , Sistema Respiratório/imunologia , Sistema Respiratório/virologia , SARS-CoV-2 , Suínos
8.
Microb Pathog ; 180: 106149, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37169314

RESUMO

The abundance of specific gut microorganisms is strongly associated with the concentrations of microbially modified bile acids. This study aimed to investigate the composition of intestinal microbiota in rats subjected to bile duct ligation or biliary drainage. Extrahepatic bile duct ligation was conducted to induce bile duct obstruction in rats. The bile was drained via a percutaneous biliary drainage catheter to cause bile deficiency. The total DNA extracted from fecal samples was sequenced with 16S DNA sequencing. Taxonomic classifications were conducted using the Mothur algorithm and SILVA138 database and were presented along with the abundance presented using a heatmap. The inter- and intra-group differences in the intestinal microbiome composition were analyzed by ANOSIM test. The biomarker microorganisms were screened using the Linear discriminant analysis Effect size method. The possible functional pathways were predicted using the Tax4Fun package. A total of 3277 operational taxonomic units (OTUs) were examined, with 2410 in the Kongbai group, 2236 in the Gengzu group, and 1763 in the Yinliu group. The composition of microorganisms at the levels of phylum, class, order, family, and genus was altered in rats with bile duct obstruction. This composition was then restored by biliary drainage. The top 10 predominant microorganisms were identified that led to the inter-group differences. Functional annotation revealed that the potential functions of the microorganisms with significant differences were enriched in metabolism, cellular processes, and genetic and environmental information processing. The intestinal microbial community was significantly changed in rats with bile duct obstruction. The changes in the abundance of intestinal microbiota Prevotellaceae and Enterobacteriaceae were statistically significant after biliary drainage treatment.


Assuntos
Colestase , Microbioma Gastrointestinal , Ratos , Animais , Drenagem/métodos , Bile , Ácidos e Sais Biliares
9.
Macromol Rapid Commun ; 44(23): e2300412, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37713720

RESUMO

Polydiacetylenes, as a class of conjugated polymers with alternating conjugated C═C and C≡C bonds, have emerged as a promising probe material for biomedical Raman imaging, given their ultrastrong Raman scattering intensity. However, the relationship between the structure, especially the molecular length of polydiacetylenes, and their Raman scattering intensity remains unclear. In this work, a series of water-soluble polydiacetylenes, namely poly(deca-4,6-diynedioic acid) (PDDA) with different molecular weights (MWs), is prepared through controlled polymerization and degradation. The ultraviolet-visible (UV-vis) absorption spectroscopic and Raman spectroscopic studies on these polymers reveal that the Raman scattering intensity of PDDA increases nonlinearly with the MW. The MW-Raman scattering intensity relationship in the polymerization process is completely different from that in the degradation process. In contrast, the Raman scattering intensity increases more linearly with the maximal absorbance of the polymer, and the relationship between the Raman scattering intensity and the maximal absorbance of PDDA in the polymerization process is consistent with that in the degradation process. The Raman scattering intensity of PDDA hence exhibits a better dependence on the effective conjugation length of the polymer, which should guide the future design of conjugated polymers for Raman imaging applications.


Assuntos
Polímeros , Análise Espectral Raman , Polímeros/química , Análise Espectral Raman/métodos , Polímero Poliacetilênico/química , Peso Molecular
10.
Environ Res ; 216(Pt 4): 114800, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36379233

RESUMO

Fe as an important redox-active transition metal plays a key role in the carbon cycle of ecosystems. To date, the mechanisms by which Fe affects organic carbon (soil respiration rate [Rs] and dissolved organic carbon [DOC] structure) remain unclear, because most studies only focused on the effect of Fe on soil organic carbon content. To understand these effects, a 30-day laboratory incubation experiment was conducted using forest swamp soils from northeastern China amended with different concentrations of exogenous Fe (no exogenous Fe added [L0], add exogenous Fe at 1 time the soil background value [L1], add exogenous Fe at 2 times the soil background value [L2]). Our results showed that exogenous Fe addition reduced the soil respiration rate by 54.8% during the incubation time. The DOC concentration decreased by 40.5% with exogenous Fe addition during the incubation time. The dissolved organic matter (DOM) characteristic parameters showed apparent variations (p < 0.05), including significant increases in the fluorescence and biological index and significant decreases in the humification index, which indicate that exogenous Fe addition reduced humification, which may lead to the increased fixation of dissolved organic carbon. In addition significant increases in tryptophan-like DOM was observed when exogenous Fe addition resulted in a soil Fe concentration of twice the background value (p < 0.05). These findings indicate that exogenous Fe addition promotes the production of endogenous soil DOC by microorganisms. Overall, Our study uses three-dimensional fluorescence spectroscopy techniques combined with the parallel factor analysis (PARAFAC) to characterize the dissolved organic matter components in soil samples under exogenous Fe addition conditions, with a view to exploring the differences in the effects of Fe on the DOC concentration and structure of wetland soils, providing a theoretical basis for the mechanisms of soil carbon fixation and soil organic matter transformation in wetland soils.


Assuntos
Solo , Áreas Alagadas , Solo/química , Carbono , Matéria Orgânica Dissolvida , Ecossistema , Taxa Respiratória , Florestas , China
11.
Cell Mol Life Sci ; 79(7): 382, 2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35751755

RESUMO

BACKGROUND: Osteosarcoma is one of the five leading causes of cancer death among all pediatric malignancies. Recent advances in non-coding RNAs suggested that many long noncoding RNAs (lncRNAs) are dysregulated in cancer tissues and play important roles in carcinogenesis. We aimed to further explore the mechanisms of Long Intergenic Non-Protein Coding RNA 313 (LINC00313)-promoted malignant phenotypes of osteosarcoma. METHODS: The mRNA expressions were determined by quantitative real-time PCR. Protein levels were detected using Western blotting or immunohistochemistry staining. Protein binding to genomic DNA and RNA were measured using chromatin and RNA immunoprecipitation assay, respectively. CCK-8 and EdU incorporation assay were adopted to detect cell proliferation. Transwell assay was employed to assess the capacity of cell migration and invasion. The roles of LINC00313 and its target genes in tumorigenesis and metastasis of osteosarcoma were evaluated using subcutaneous xenograft models and tail vein inoculation models. RESULTS: LINC00313 was elevated in osteosarcoma tissues compared with adjacent normal tissues. Higher LINC00313 was associated with advanced grades of osteosarcoma. LINC00313 promoted cell proliferation, migration, invasion in vitro and tumor growth as well as metastasis in vivo through inhibiting PTEN expression to promote AKT phosphorylation. Mechanistically, LINC00313 favored the interaction between FUS and EZH2, leading to the prolonged half-life of EZH2 mRNA, thereby in turn up-regulating EZH2 proteins and increasing EZH2-mediated epigenetic silence of PTEN. CONCLUSION: LINC00313 exerted oncogene-like actions through increasing EZH2 mRNA stability, leading to PTEN deficiency in osteosarcoma.


Assuntos
Neoplasias Ósseas , Osteossarcoma , RNA Longo não Codificante , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Osteossarcoma/genética , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Estabilidade de RNA/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética
12.
Opt Lett ; 47(22): 6021-6024, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37219162

RESUMO

An autoencoder-residual (AE-Res) network is designated to assist the linearization of the wideband photonic scanning channelized receiver. It is capable of adaptively suppressing spurious distortions over multiple octaves of signal bandwidth, obviating the need for calculating the multifactorial nonlinear transfer functions. Proof-of-concept experiments indicate that the improvement of the third-order spur-free dynamic range (SFDR2/3) is 17.44 dB. Moreover, the results for real wireless communication signals demonstrate that the improvement of the spurious suppression ratio (SSR) is 39.69 dB and the reduction of the noise floor is ∼10 dB.

13.
BMC Bioinformatics ; 22(1): 231, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952199

RESUMO

BACKGROUND: Epitope prediction is a useful approach in cancer immunology and immunotherapy. Many computational methods, including machine learning and network analysis, have been developed quickly for such purposes. However, regarding clinical applications, the existing tools are insufficient because few of the predicted binding molecules are immunogenic. Hence, to develop more potent and effective vaccines, it is important to understand binding and immunogenic potential. Here, we observed that the interactive association constituted by human leukocyte antigen (HLA)-peptide pairs can be regarded as a network in which each HLA and peptide is taken as a node. We speculated whether this network could detect the essential interactive propensities embedded in HLA-peptide pairs. Thus, we developed a network-based deep learning method called DeepNetBim by harnessing binding and immunogenic information to predict HLA-peptide interactions. RESULTS: Quantitative class I HLA-peptide binding data and qualitative immunogenic data (including data generated from T cell activation assays, major histocompatibility complex (MHC) binding assays and MHC ligand elution assays) were retrieved from the Immune Epitope Database database. The weighted HLA-peptide binding network and immunogenic network were integrated into a network-based deep learning algorithm constituted by a convolutional neural network and an attention mechanism. The results showed that the integration of network centrality metrics increased the power of both binding and immunogenicity predictions, while the new model significantly outperformed those that did not include network features and those with shuffled networks. Applied on benchmark and independent datasets, DeepNetBim achieved an AUC score of 93.74% in HLA-peptide binding prediction, outperforming 11 state-of-the-art relevant models. Furthermore, the performance enhancement of the combined model, which filtered out negative immunogenic predictions, was confirmed on neoantigen identification by an increase in both positive predictive value (PPV) and the proportion of neoantigen recognition. CONCLUSIONS: We developed a network-based deep learning method called DeepNetBim as a pan-specific epitope prediction tool. It extracted the attributes of the network as new features from HLA-peptide binding and immunogenic models. We observed that not only did DeepNetBim binding model outperform other updated methods but the combination of our two models showed better performance. This indicates further applications in clinical practice.


Assuntos
Aprendizado Profundo , Algoritmos , Epitopos , Antígenos HLA/genética , Antígenos HLA/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe II , Humanos , Ligação Proteica
14.
Genet Mol Biol ; 44(2): e20200365, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33821876

RESUMO

The Irrawaddy dolphin (Orcaella brevirostris) is an endangered, small cetacean species which is widely distributed in rivers, estuaries, and coastal waters throughout the tropical and subtropical Indo-Pacific. Despite the extensive distribution of this species, little is known of individual movements or genetic exchange among regions in Thailand. Here, we evaluate the genetic diversity and genetic structure of O. brevirostris in the eastern, northern and western Gulf of Thailand, and Andaman Sea. Although phylogenetic relationships and network analysis based on 15 haplotypes obtained from 32 individuals reveal no obvious divergence, significant genetic differentiation in mitochondrial DNA (overall FST = 0.226, P < 0.001; ΦST = 0.252, P < 0.001) is apparent among regions. Of 18 tested microsatellite loci, 10 are polymorphic and successfully characterized in 28 individuals, revealing significant genetic differentiation (overall FST = 0.077, P < 0.05) among the four sampling sites. Structure analysis reveals two inferred genetic clusters. Additionally, Mantel analysis demonstrates individual-by-individual genetic distances and geographic distances follow an isolation-by-distance model. We speculate that the significant genetic structure of O. brevirostris in Thailand is associated with a combination of geographical distribution patterns, environmental and anthropogenic factors, and local adaptations.

15.
Cancer Sci ; 111(12): 4558-4566, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32970347

RESUMO

Diagnostic markers for both colorectal cancer (CRC) and its precursor lesions are lacking. Although aberrant methylation of the secretin receptor (SCTR) gene was observed in CRC, the diagnostic performance has not been evaluated. Therefore, this study aimed to assess and verify the diagnostic value of SCTR methylation of CRC and its precursor lesions through integrating the largest methylation data. The diagnostic performance of SCTR methylation was analyzed in the discovery set from The Cancer Genome Atlas (TCGA) CRC methylation data (N = 440), and verified in a large-scale test set (N = 938) from the Gene Expression Omnibus (GEO). Targeted bisulfite sequencing analysis was developed and applied to detect the methylation status of SCTR in our independent validation set (N = 374). Our findings revealed that the SCTR gene was frequently hypermethylated at its CpG islands in CRC. In the TCGA discovery set, the diagnostic score was constructed using 4 CpG sites (cg01013590, cg20505223, cg07176264, and cg26009192) and achieved high diagnostic performance (area under the ROC curve [AUC] = 0.964). In the GEO test set, the diagnostic score had robust diagnostic ability to distinguish CRC (AUC = 0.948) and its precursor lesions (AUC = 0.954) from normal samples. Moreover, hypermethylation of the SCTR gene was also found in cell-free DNA samples collected from CRC patients, but not in those from healthy controls. In the validation set, consistent results were observed using the targeted bisulfite sequencing array. Our study highlights that hypermethylation at CpG islands of the SCTR gene is a potential diagnostic biomarker in CRCs and its precursor lesions.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores dos Hormônios Gastrointestinais/metabolismo , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres , Neoplasias Colorretais/diagnóstico , Ilhas de CpG , Expressão Gênica , Humanos , Leucócitos/metabolismo , Metilação , Análise Serial de Proteínas , Receptores Acoplados a Proteínas G/genética , Receptores dos Hormônios Gastrointestinais/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
Chemistry ; 26(9): 2041-2050, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31785014

RESUMO

A green and convenient solid-state method assisted by mechanical energy is employed for the synthesis of boron (B) and nitrogen (N) co-doped porous carbons (B,N-Cs). Glutamic acid (Glu) and boric acid (H3 BO3 ) are used as the N-containing carbon precursor and boron source, respectively. This method is easy to perform and proved to be efficient towards co-doping B and N into the carbon matrix with high contents of B (7 atom %) and N (10 atom %). By adjusting the molar ratio of H3 BO3 to Glu, the surface chemical states of B and N could be readily modulated. When increasing H3 BO3 dosage, the pore size of B,N-Cs could be tuned ranging from micropores to mesopores with a Brunauer-Emmett-Teller (BET) surface area up to 940 m2 g-1 . Finally, the B,N-Cs were applied as metal-free catalysts for the cycloaddition of CO2 to epoxides, which outperform the N-doped carbon catalyst (NC-900) and the physically mixed catalyst of NC-900/B4 C. The enhanced activity is attributed to the cooperative effect between B and N sites. X-ray photoelectron spectroscopy (XPS) analysis reveals that BN3 in the B,N-Cs serves as a critical active site for the cooperative catalysis.

18.
Trends Genet ; 32(12): 815-827, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27836208

RESUMO

Geneticists have long sought the ability to manipulate vertebrate genomes by directly altering the information encoded in specific genes. The recently discovered clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonuclease has the ability to bind single loci within vertebrate genomes and generate double-strand breaks (DSBs) at those sites. These DSBs induce an endogenous DSB repair response that results in small insertions or deletions at the targeted site. Alternatively, a template can be supplied, in which case homology-directed repair results in the generation of engineered alleles at the break site. These changes alter the function of the targeted gene facilitating the analysis of gene function. This tool has been widely adopted in the zebrafish model; we discuss the development of this system in the zebrafish and how it can be manipulated to facilitate genome engineering.


Assuntos
Sistemas CRISPR-Cas/genética , Engenharia Genética , Peixe-Zebra/genética , Animais , Quebras de DNA de Cadeia Dupla , Deleção de Genes , Genoma , Mutagênese Insercional
19.
Bioconjug Chem ; 30(1): 29-33, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30585717

RESUMO

Amyloid fibril assembly is associated with many human disorders, and to approach an inhibitor of amyloid formation that is effective at ultralow stoichiometric concentrations remains a big challenge. Taking fibril assembly of human islet amyloid polypeptide (IAPP) as a model system, we demonstrate here that conjugating a rationally designed sequence-specific nanobody inhibitor M1 with gold nanoparticles (AuNPs) can significantly enhance the inhibition potency of M1, leading to complete inhibition of IAPP amyloid fibrillation at very low M1:IAPP molar ratios. Thioflavin T kinetics fluorescence assays, dynamic light scattering measurements, far-UV circular dichroism, and transmission electron microscopy all indicate that M1-AuNP conjugates prevent IAPP fibrillation at M1:IAPP molar ratios of as low as 1:50, while free M1 is unable to prevent fibrillation at the same substoichiometric concentrations. This strategy represents a prototype of the facile development of a variety of highly potent amyloid inhibitors with enhanced therapeutic effects.


Assuntos
Ouro/química , Imunoconjugados/química , Imunoconjugados/imunologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/imunologia , Nanopartículas Metálicas/química , Anticorpos de Domínio Único/imunologia , Sequência de Aminoácidos , Animais , Benzotiazóis/química , Materiais Biocompatíveis , Dicroísmo Circular , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Cinética , Microscopia Eletrônica de Transmissão , Ratos
20.
Clin Oral Investig ; 23(4): 1615-1623, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30145662

RESUMO

BACKGROUND: It is more common to need dual antiplatelet therapy (DAPT) for patients who had recently inserted coronary artery stent. However, the postoperative bleeding risk of patients in DAPT could significantly increase. The dental management of patients with antithrombotic therapy has always been a controversial problem. Focusing on this issue, this review discussed the available evidence to provide optimal strategy for patients taking dual antiplatelet agents in the dental setting. METHODS: We searched the PubMed, Embase, ScienceDirect, Web of Science (WOS), Cochrane Library, and China National Knowledge Infrastructure (CNKI) which was performed in May 2018. Relevant articles were included according to our inclusion and exclusion criteria. Meta-analysis was conducted with fixed effects models. Subgroup analysis was used due to different dental surgeries. RESULTS: Our meta-analysis included ten studies (continue DAPT vs. placebo, 535 patients vs.2907 patients). The quantitative results indicated that the risk of postoperative bleeding with continuing DAPT experienced significantly increase (RR = 1.95 95% CI [1.07, 3.54]; p = 0.03). There was no statistically significant difference between the postoperative bleeding rate and different dental surgeries (p = 0.72). CONCLUSION: On the current studies, postoperative hemorrhage is exacerbated with DAPT, but it could be controlled by enhancing hemostasis methods. We recommend continuing long-term DAPT before tooth extraction. CLINICAL RELEVANCE: In this work, we systematically evaluated and summarized the results of small clinical trials after reviewing the present literatures on this topic, so that we could propose more objective and more accurate evidence-based recommendations on dental management for patient with dual antiplatelet therapy.


Assuntos
Terapia Antiplaquetária Dupla , Inibidores da Agregação Plaquetária , Hemorragia Pós-Operatória , China , Assistência Odontológica , Quimioterapia Combinada , Terapia Antiplaquetária Dupla/efeitos adversos , Humanos
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