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1.
Proc Natl Acad Sci U S A ; 119(29): e2205827119, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35858338

RESUMO

Heterogeneous bubble nucleation is one of the most fundamental interfacial processes ranging from nature to technology. There is excellent evidence that surface topology is important in directing heterogeneous nucleation; however, deep understanding of the energetics by which nanoscale architectures promote nucleation is still challenging. Herein, we report a direct and quantitative measurement of single-bubble nucleation on a single silica nanoparticle within a microsized droplet using scanning electrochemical cell microscopy. Local gas concentration at nucleation is determined from finite element simulation at the corresponding faradaic current of the peak-featured voltammogram. It is demonstrated that the criteria gas concentration for nucleation first drops and then rises with increasing nanoparticle radius. An optimum nanoparticle radius around 10 nm prominently expedites the nucleation by facilitating the special topological nanoconfinements that consequently catalyze the nucleation. Moreover, the experimental result is corroborated by our theoretical calculations of free energy change based on the classic nucleation theory. This study offers insights into the impact of surface topology on heterogenous nucleation that have not been previously observed.

2.
Genet Sel Evol ; 56(1): 28, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594607

RESUMO

BACKGROUND: Enhancer RNAs (eRNAs) play a crucial role in transcriptional regulation. While significant progress has been made in understanding epigenetic regulation mediated by eRNAs, research on the construction of eRNA-mediated gene regulatory networks (eGRN) and the identification of critical network components that influence complex traits is lacking. RESULTS: Here, employing the pig as a model, we conducted a comprehensive study using H3K27ac histone ChIP-seq and RNA-seq data to construct eRNA expression profiles from multiple tissues of two distinct pig breeds, namely Enshi Black (ES) and Duroc. In addition to revealing the regulatory landscape of eRNAs at the tissue level, we developed an innovative network construction and refinement method by integrating RNA-seq, ChIP-seq, genome-wide association study (GWAS) signals and enhancer-modulating effects of single nucleotide polymorphisms (SNPs) measured by self-transcribing active regulatory region sequencing (STARR-seq) experiments. Using this approach, we unraveled eGRN that significantly influence the growth and development of muscle and fat tissues, and identified several novel genes that affect adipocyte differentiation in a cell line model. CONCLUSIONS: Our work not only provides novel insights into the genetic basis of economic pig traits, but also offers a generalizable approach to elucidate the eRNA-mediated transcriptional regulation underlying a wide spectrum of complex traits for diverse organisms.


Assuntos
Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Animais , Suínos/genética , Epigênese Genética , Regulação da Expressão Gênica , Músculos
3.
BMC Musculoskelet Disord ; 25(1): 428, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824518

RESUMO

OBJECTIVE: To develop an AI-assisted MRI model to identify surgical target areas in pediatric hip and periarticular infections. METHODS: A retrospective study was conducted on the pediatric patients with hip and periarticular infections who underwent Magnetic Resonance Imaging(MRI)examinations from January 2010 to January 2023 in three hospitals in China. A total of 7970 axial Short Tau Inversion Recovery (STIR) images were selected, and the corresponding regions of osteomyelitis (label 1) and abscess (label 2) were labeled using the Labelme software. The images were randomly divided into training group, validation group, and test group at a ratio of 7:2:1. A Mask R-CNN model was constructed and optimized, and the performance of identifying label 1 and label 2 was evaluated using receiver operating characteristic (ROC) curves. Calculation of the average time it took for the model and specialists to process an image in the test group. Comparison of the accuracy of the model in the interpretation of MRI images with four orthopaedic surgeons, with statistical significance set at P < 0.05. RESULTS: A total of 275 patients were enrolled, comprising 197 males and 78 females, with an average age of 7.10 ± 3.59 years, ranging from 0.00 to 14.00 years. The area under curve (AUC), accuracy, sensitivity, specificity, precision, and F1 score for the model to identify label 1 were 0.810, 0.976, 0.995, 0.969, 0.922, and 0.957, respectively. The AUC, accuracy, sensitivity, specificity, precision, and F1 score for the model to identify label 2 were 0.890, 0.957, 0.969, 0.915, 0.976, and 0.972, respectively. The model demonstrated a significant speed advantage, taking only 0.2 s to process an image compared to average 10 s required by the specialists. The model identified osteomyelitis with an accuracy of 0.976 and abscess with an accuracy of 0.957, both statistically better than the four orthopaedic surgeons, P < 0.05. CONCLUSION: The Mask R-CNN model is reliable for identifying surgical target areas in pediatric hip and periarticular infections, offering a more convenient and rapid option. It can assist unexperienced physicians in pre-treatment assessments, reducing the risk of missed and misdiagnosis.


Assuntos
Imageamento por Ressonância Magnética , Osteomielite , Humanos , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Criança , Estudos Retrospectivos , Adolescente , Osteomielite/diagnóstico por imagem , Pré-Escolar , Lactente , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Articulação do Quadril/patologia , China , Abscesso/diagnóstico por imagem , Abscesso/cirurgia , Curva ROC
4.
PLoS Genet ; 17(11): e1009910, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34780471

RESUMO

Natural and artificial directional selections have resulted in significantly genetic and phenotypic differences across breeds in domestic animals. However, the molecular regulation of skeletal muscle diversity remains largely unknown. Here, we conducted transcriptome profiling of skeletal muscle across 27 time points, and performed whole-genome re-sequencing in Landrace (lean-type) and Tongcheng (obese-type) pigs. The transcription activity decreased with development, and the high-resolution transcriptome precisely captured the characterizations of skeletal muscle with distinct biological events in four developmental phases: Embryonic, Fetal, Neonatal, and Adult. A divergence in the developmental timing and asynchronous development between the two breeds was observed; Landrace showed a developmental lag and stronger abilities of myoblast proliferation and cell migration, whereas Tongcheng had higher ATP synthase activity in postnatal periods. The miR-24-3p driven network targeting insulin signaling pathway regulated glucose metabolism. Notably, integrated analysis suggested SATB2 and XLOC_036765 contributed to skeletal muscle diversity via regulating the myoblast migration and proliferation, respectively. Overall, our results provide insights into the molecular regulation of skeletal muscle development and diversity in mammals.


Assuntos
Proteínas de Ligação à Região de Interação com a Matriz/genética , MicroRNAs/genética , Músculo Esquelético/crescimento & desenvolvimento , RNA Longo não Codificante/genética , Suínos/embriologia , Transcriptoma/genética , Animais , Diferenciação Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Deriva Genética , Genoma/genética , Desenvolvimento Muscular/genética , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , RNA Longo não Codificante/metabolismo , Suínos/genética , Suínos/metabolismo
5.
J Med Virol ; 95(2): e28513, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36661039

RESUMO

Mpox is caused by the mpox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. Animal hosts, such as African rodents, mice, prairie dogs, and non-human primates, play important roles in the development and transmission of outbreaks. Laboratory animal infection experiments have demonstrated that some animals are susceptible to mpox virus. This review summarizes the current progress on the animal hosts for mpox virus. The surveillance of mpox virus in animal hosts will provide important insights into virus tracing, analysis of mutation evolutionary patterns, transmission mechanisms, and development of control measures.


Assuntos
Monkeypox virus , Mpox , Animais , Camundongos , Especificidade de Hospedeiro , Primatas/virologia , Sciuridae/virologia , Mpox/veterinária
6.
Macromol Rapid Commun ; 44(11): e2200778, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36404104

RESUMO

Covalent organic frameworks (COFs) are a type of crystalline porous polymers that possess ordered structures and eternal pores. Because of their unique structural characteristics and diverse functional groups, COFs have been used in various application fields, such as adsorption, catalysis, separation, ion conduction, and energy storage. Among COFs, the fluorine-containing COFs (fCOFs) have been developed for special applications by virtue of special physical and chemical properties resulting from fluorine element, which is a nonmetallic halogen element and possesses strong electronegativity. In the organic chemistry field, introducing fluorine into chemicals enables those chemicals to exhibit many interesting properties, and fluorine chemistry increasingly plays an important role in the history of chemical development. The introduction of fluorine in COFs can enhance the crystallinity, porosity, and stability of COFs, making COFs having superior performances and some new applications. In this review, the synthesis and application of fCOFs are systematically summarized. The application involves photocatalytic production of hydrogen peroxide, photocatalytic water splitting, electrocatalytic CO2 reduction, adsorption for different substances (H2 , pesticides, per-/polyfluoroalkyl substances, polybrominated diphenyl ethers, bisphenols, and positively charged organic dye molecules), oil-water separation, energy storage (e.g., zinc-ion batteries, lithium-sulfur batteries), and proton conduction. Perspectives of remaining challenges and possible directions for fCOFs are also discussed.


Assuntos
Flúor , Estruturas Metalorgânicas , Halogênios , Polímeros
7.
Int J Mol Sci ; 24(15)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37569400

RESUMO

Utilizing large-scale epigenomics data, deep learning tools can predict the regulatory activity of genomic sequences, annotate non-coding genetic variants, and uncover mechanisms behind complex traits. However, these tools primarily rely on human or mouse data for training, limiting their performance when applied to other species. Furthermore, the limited exploration of many species, particularly in the case of livestock, has led to a scarcity of comprehensive and high-quality epigenetic data, posing challenges in developing reliable deep learning models for decoding their non-coding genomes. The cross-species prediction of the regulatory genome can be achieved by leveraging publicly available data from extensively studied organisms and making use of the conserved DNA binding preferences of transcription factors within the same tissue. In this study, we introduced DeepSATA, a novel deep learning-based sequence analyzer that incorporates the transcription factor binding affinity for the cross-species prediction of chromatin accessibility. By applying DeepSATA to analyze the genomes of pigs, chickens, cattle, humans, and mice, we demonstrated its ability to improve the prediction accuracy of chromatin accessibility and achieve reliable cross-species predictions in animals. Additionally, we showcased its effectiveness in analyzing pig genetic variants associated with economic traits and in increasing the accuracy of genomic predictions. Overall, our study presents a valuable tool to explore the epigenomic landscape of various species and pinpoint regulatory deoxyribonucleic acid (DNA) variants associated with complex traits.


Assuntos
Aprendizado Profundo , Animais , Humanos , Bovinos , Suínos , Camundongos , Galinhas/genética , Cromatina/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , DNA
8.
J Integr Plant Biol ; 65(3): 633-645, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36269601

RESUMO

Whole-genome genotyping methods are important for breeding. However, it has been challenging to develop a robust method for simultaneous foreground and background genotyping that can easily be adapted to different genes and species. In our study, we accidently discovered that in adapter ligation-mediated PCR, the amplification by primer-template mismatched annealing (PTMA) along the genome could generate thousands of stable PCR products. Based on this observation, we consequently developed a novel method for simultaneous foreground and background integrated genotyping by sequencing (FBI-seq) using one specific primer, in which foreground genotyping is performed by primer-template perfect annealing (PTPA), while background genotyping employs PTMA. Unlike DNA arrays, multiple PCR, or genome target enrichments, FBI-seq requires little preliminary work for primer design and synthesis, and it is easily adaptable to different foreground genes and species. FBI-seq therefore provides a prolific, robust, and accurate method for simultaneous foreground and background genotyping to facilitate breeding in the post-genomics era.


Assuntos
Genoma , Genótipo , Primers do DNA/genética , Reação em Cadeia da Polimerase/métodos
9.
Biochem Cell Biol ; 100(2): 142-151, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34990285

RESUMO

Metformin, a traditional first-line pharmacological treatment for type 2 diabetes, has recently been shown to have anti-cancer effects on hepatocellular carcinoma (HCC). However, the molecular mechanism underlying the anti-tumor activity of metformin remains unclear. The Sonic hedgehog (Shh) signaling pathway is closely associated with the initiation and progression of HCC. Therefore, the aim of the current study was to investigate the effects of metformin on the biological behavior of HCC and the underlying functional mechanism of metformin in the Shh pathway. HCC was induced in HepG2 cells using recombinant human Shh (rhShh). The effects of metformin on proliferation and metastasis were evaluated using in vitro proliferation, wound healing, and invasion assays. The mRNA and protein expression levels of proteins related to the Shh pathway were measured using western blotting, quantitative PCR, and immunofluorescence staining. Metformin inhibited rhShh-induced proliferation and metastasis. Furthermore, metformin decreased the mRNA and protein expression of Shh pathway components, including Shh, Ptch, Smo, and Gli-1. Silencing of AMPK in the presence of metformin revealed that metformin exerted its inhibitory effects via AMPK. Our findings demonstrate that metformin suppresses the migration and invasion of HepG2 cells via AMPK-mediated inhibition of the Shh pathway.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Metformina , Proteínas Quinases Ativadas por AMP/metabolismo , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Metformina/farmacologia , Transdução de Sinais , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína GLI1 em Dedos de Zinco/farmacologia
10.
J Org Chem ; 87(10): 6807-6811, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35507767

RESUMO

We report herein the synthesis of 1,3-enynes via palladium-catalyzed cross-coupling between enone derivatives and alkynylsilanes. The employment of an appropriate pyridine-oxazoline ligand is the key to the C-C cleavage and the high E/Z stereoselectivity. This protocol features broad substrate scope and wide functional-group tolerance, affording the desired products in moderate-to-good yields. Late-stage diversification of natural product ß-ionone further demonstrated the synthetic utility of this protocol.


Assuntos
Paládio , Catálise , Ligantes , Paládio/química
11.
Cell Biol Int ; 46(2): 213-221, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34719075

RESUMO

Sorafenib is the important first-standard drug for patients with advanced hepatocellular carcinoma (HCC). A major obstacle to successful treatment is sorafenib resistance. However, the mechanism of sorafenib resistance is unclear. The present study aimed to determine the involvement of dipeptidyl peptidase-8 (DPP8) in sorafenib resistance. DPP8 expression was detected using quantitative real-time PCR (qPCR) and western blot analysis. The effect of DPP8 on sorafenib resistance was examined using terminal deoxynulceotidyl transferase nick-end-labeling (TUNEL), colony formation, flow cytometry, luciferase reporter, immunofluorescence, and immunoprecipitation (IP) assays. We found that DPP8 mRNA and protein levels were dramatically upregulated in HCC. Gene set enrichment analysis (GSEA) illustrated that DPP8 might be involved in apoptosis regulation. Downregulation of DPP8 substantially promoted the sensitivity of HCC cells to sorafenib. Further analysis showed that DPP8 might regulate nuclear factor kappa B (NF-κB) signaling, which was confirmed using a luciferase reporter assay. Downregulation of DPP8 decreased the expression levels of downstream genes of the NF-κB pathway. IP showed that DPP8 can interact with NF-κB subunit c-Rel, an important protein of NF-κB signaling. Finally, a drug combination of sorafenib and Val-boroPro induced higher mortality of HCC cells than sorafenib alone in DPP8-upregulated cells. Our findings indicated that using the inhibitor Val-boroPro might be a promising method to enhance sorafenib sensitivity in advanced HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptose , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Dipeptidil Peptidases e Tripeptidil Peptidases/metabolismo , Dipeptidil Peptidases e Tripeptidil Peptidases/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , NF-kappa B/metabolismo , Sorafenibe/farmacologia
12.
Genet Sel Evol ; 54(1): 62, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104777

RESUMO

BACKGROUND: The genetic mechanisms that underlie phenotypic differentiation in breeding animals have important implications in evolutionary biology and agriculture. However, the contribution of cis-regulatory variants to pig phenotypes is poorly understood. Therefore, our aim was to elucidate the molecular mechanisms by which non-coding variants cause phenotypic differences in pigs by combining evolutionary biology analyses and functional genomics. RESULTS: We obtained a high-resolution phased chromosome-scale reference genome with a contig N50 of 18.03 Mb for the Luchuan pig breed (a representative eastern breed) and profiled potential selective sweeps in eastern and western pigs by resequencing the genomes of 234 pigs. Multi-tissue transcriptome and chromatin accessibility analyses of these regions suggest that tissue-specific selection pressure is mediated by promoters and distal cis-regulatory elements. Promoter variants that are associated with increased expression of the lysozyme (LYZ) gene in the small intestine might enhance the immunity of the gastrointestinal tract and roughage tolerance in pigs. In skeletal muscle, an enhancer-modulating single-nucleotide polymorphism that is associated with up-regulation of the expression of the troponin C1, slow skeletal and cardiac type (TNNC1) gene might increase the proportion of slow muscle fibers and affect meat quality. CONCLUSIONS: Our work sheds light on the molecular mechanisms by which non-coding variants shape phenotypic differences in pigs and provides valuable resources and novel perspectives to dissect the role of gene regulatory evolution in animal domestication and breeding.


Assuntos
Genoma , Genômica , Animais , Evolução Molecular , Fenótipo , Análise de Sequência de DNA , Suínos/genética
13.
J Chem Phys ; 156(10): 104701, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35291796

RESUMO

The microstructural features and charge-potential relation of an electric double layer (EDL) at a stepped Pt(553)/water interface are investigated using ab initio molecular dynamics simulation. The results indicate that the chemisorbed O-down water molecules gather at the (110) step sites, while the (111) terrace sites are covered by the H-down water molecules, which greatly weakens the push-back effect of interface water on the spillover electrons of the stepped surface and, therefore, results in a much more positive potential of zero charge (PZC) than the extended low-index Pt surfaces. It is further revealed that around the PZC, the change in the surface charge density is dominated by the change in the coverage of chemisorbed water molecules, while EDL charging is the main cause of the change in the surface charge density at potential away from the PZC, thus leading to an S-shaped charge-potential relation and a maximum interface capacitance around PZC. Our results make up for the current lack of the atomic-scale understanding of the EDL microstructures and charge-potential relation on the real electrode surfaces with plentiful step and defect sites.

14.
J Clin Nurs ; 31(11-12): 1620-1627, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34459049

RESUMO

BACKGROUND: The vital-sign monitoring strategy of patients with acute aortic dissection in the emergency department is mainly based on traditional experience. This study attempts to explore the significance of the national early warning score (NEWS) in monitoring the condition of patients with acute aortic dissection during emergency observation and to provide evidence for emergency nurses in optimal and scientific monitoring of patients. METHODS: The case-control method was used to continuously enrol patients with acute aortic dissection who had been in the emergency department; the STROBE checklist was used in this process. Based on patients' clinical deterioration, they were divided into two groups: clinical deterioration and non-clinical deterioration. The NEWS at each time point was compared by independent-samples t-test, and the predictive power of NEWS was evaluated according to the area under the receiver operating characteristic curve. RESULTS: A total of 290 patients with acute aortic dissection were included: 46 patients showed clinical deterioration and 244 did not. There were significant differences in the NEW scores of the two groups at admission time and at 12, 8, 4 and 0.5 h before clinical deterioration. The NEW scores of the clinical deterioration group showed an upward trend, while the non-clinical deterioration group showed a relatively stable trend. The NEWS can be used to predict the occurrence of clinical deterioration earlier at 4 h before clinical deterioration. Simultaneously, the patient's respiration rate and SpO2 had better predictive performance than other vital signs. CONCLUSION: The NEWS can be used to triage patients with acute aortic dissection admitted to the emergency department. Continuous use of the NEWS for monitoring can play a vital role in early warning of clinical deterioration in patients with acute aortic dissection. In clinical care, attention should also be paid when patients with acute aortic dissection have abnormal respiration rate and SpO2 .


Assuntos
Dissecção Aórtica , Deterioração Clínica , Escore de Alerta Precoce , Dissecção Aórtica/diagnóstico , Estudos de Casos e Controles , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Curva ROC , Estudos Retrospectivos
15.
Int J Mol Sci ; 23(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35682680

RESUMO

Myogenesis is a central step in prenatal myofiber formation, postnatal myofiber hypertrophy, and muscle damage repair in adulthood. RNA-Seq technology has greatly helped reveal the molecular mechanism of myogenesis, but batch effects in different experiments inevitably lead to misinterpretation of differentially expressed genes (DEGs). We previously applied the robust rank aggregation (RRA) method to effectively circumvent batch effects across multiple RNA-Seq datasets from 3T3-L1 cells. Here, we also used the RRA method to integrate nine RNA-Seq datasets from C2C12 cells and obtained 3140 robust DEGs between myoblasts and myotubes, which were then validated with array expression profiles and H3K27ac signals. The upregulated robust DEGs were highly enriched in gene ontology (GO) terms related to muscle cell differentiation and development. Considering that the cooperative binding of transcription factors (TFs) to enhancers to regulate downstream gene expression is a classical epigenetic mechanism, differentially expressed TFs (DETFs) were screened, and potential novel myogenic factors (MAF, BCL6, and ESR1) with high connection degree in protein-protein interaction (PPI) network were presented. Moreover, KLF5 cooperatively binds with the three key myogenic factors (MYOD, MYOG, and MEF2D) in C2C12 cells. Motif analysis speculates that the binding of MYOD and MYOG is KLF5-independent, while MEF2D is KLF5-dependent. It was revealed that KLF5-binding sites could be exploited to filter redundant MYOD-, MYOG-, and MEF2D-binding sites to focus on key enhancers for myogenesis. Further functional annotation of KLF5-binding sites suggested that KLF5 may regulate myogenesis through the PI3K-AKt signaling pathway, Rap1 signaling pathway, and the Hippo signaling pathway. In general, our study provides a wealth of untapped candidate targets for myogenesis and contributes new insights into the core regulatory mechanisms of myogenesis relying on KLF5-binding signal.


Assuntos
Desenvolvimento Muscular , Fosfatidilinositol 3-Quinases , Diferenciação Celular/genética , Desenvolvimento Muscular/genética , Mioblastos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fatores de Transcrição/metabolismo
16.
Pak J Pharm Sci ; 35(4): 1055-1066, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36008902

RESUMO

The present study aimed to evaluate the spectrum-effect relationships between high-performance liquid chromatography fingerprints and anti-inflammatory effects of Tetrastigma planicaule(Hook.)Gagnep. Chemical fingerprints of ten batches of Tetrastigma planicaule from various sources were obtained by HPLC. The anti-inflammatory activity was investigated by a model of ear swelling in mice caused by xylene and a model of cotton pellet granuloma. Hierarchical cluster analysis (HCA) results showed that all the samples were clustered into four categories, which was basically consistent with the principal component analysis (PCA) results. The results of the joint grey relational analysis (GRA) and partial least squares regression analysis (PLSR) showed that peaks 1, 2 and 12 were positively correlated with the anti-acute inflammatory effect (ear swelling) in mice, and peaks 3, 5, 6 and 11 were positively correlated with the anti-chronic inflammatory effect (cotton pellet granuloma) in mice. The anti-inflammatory effect of Tetrastigma planicaule is the result of the synergistic effect of multiple components, which provides a basis for further exploring the anti-inflammatory substances and quality evaluation of the herb.


Assuntos
Medicamentos de Ervas Chinesas , Vitaceae , 1-Butanol , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Camundongos , Análise de Componente Principal
17.
Am J Hum Genet ; 102(6): 1031-1047, 2018 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-29754769

RESUMO

Analysis of de novo mutations (DNMs) from sequencing data of nuclear families has identified risk genes for many complex diseases, including multiple neurodevelopmental and psychiatric disorders. Most of these efforts have focused on mutations in protein-coding sequences. Evidence from genome-wide association studies (GWASs) strongly suggests that variants important to human diseases often lie in non-coding regions. Extending DNM-based approaches to non-coding sequences is challenging, however, because the functional significance of non-coding mutations is difficult to predict. We propose a statistical framework for analyzing DNMs from whole-genome sequencing (WGS) data. This method, TADA-Annotations (TADA-A), is a major advance of the TADA method we developed earlier for DNM analysis in coding regions. TADA-A is able to incorporate many functional annotations such as conservation and enhancer marks, to learn from data which annotations are informative of pathogenic mutations, and to combine both coding and non-coding mutations at the gene level to detect risk genes. It also supports meta-analysis of multiple DNM studies, while adjusting for study-specific technical effects. We applied TADA-A to WGS data of ∼300 autism-affected family trios across five studies and discovered several autism risk genes. The software is freely available for all research uses.


Assuntos
Mapeamento Cromossômico , Predisposição Genética para Doença , Mutação/genética , Estatística como Assunto , Sequenciamento Completo do Genoma , Transtorno Autístico/genética , Calibragem , Elementos Facilitadores Genéticos/genética , Humanos , Anotação de Sequência Molecular , Taxa de Mutação , Splicing de RNA/genética , Fatores de Risco , Sequenciamento do Exoma
18.
Cell Biol Int ; 45(9): 1906-1916, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33969575

RESUMO

Sorafenib was the first systemic therapy approved by the Food and Drug Administration to treat advanced hepatocellular carcinoma (HCC). However, sorafenib therapy is frequently accompanied by drug resistance. We aimed to explore the mechanisms of sorafenib resistance and provide feasible solutions to increase the response to sorafenib in patients with advanced HCC. The expression profile of discoidin domain receptor 2 (DDR2) in HCC tissues and cells was detected using quantitative real-time PCR (qPCR) and western blotting assays. The effects of DDR2 on sorafenib resistance were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation, TdT-mediated dUTP nick end labeling, and flow cytometry assays. The effect of DDR2 on the nuclear factor kappa B (NF-κB) signaling pathway was evaluated by luciferase reporter, immunofluorescence, qPCR and flow cytometry assays. We demonstrated that DDR2 expression was dramatically upregulated in sorafenib-resistant HCC tissues relative to sensitive tissues. Downregulation of DDR2 sensitized HCC cell lines to sorafenib cytotoxicity. Further analysis showed that DDR2 could increase the nuclear location of REL proto-oncogene, a NF-κB subunit, to mediate NF-κB signaling. Blocking NF-κB signaling using the NF-κB signaling inhibitor, bardoxolone methyl, increased the response of HCC cells to sorafenib. Further analysis showed that DNA amplification of DDR2 is an important mechanism leading to DDR2 overexpression in HCC. Our results demonstrated that DDR2 is a potential therapeutic target in patients with HCC, and targeting DDR2 represents a promising approach to increase sorafenib sensitivity in patients with HCC.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Receptor com Domínio Discoidina 2/fisiologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/farmacologia , Adulto , Idoso , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Nanotechnology ; 32(47)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34384073

RESUMO

Lithium-sulfur battery is expected to become a new generation of commercial battery owing to its ultra-high theoretical specific capacity, low-cost, and environmental benign. However, the inherent insulation of sulfur and the shuttle effect of lithium polysulfide between electrodes limit the application of lithium-sulfur battery. In order to solve these problems, we focus on the design of carbon-sulfur composite structure. Herein, CS-CNTs homojunctions featured with the carbon nanotubes (CNTs)in situgrown on carbon sphere (CS) is designed and synthesized by simple polymerization and heat treatment. The composites of CS with interconnected pore networks and CNTs with high conductivity not only offer a conductive framework to promote fast electron transmission, but also provide a larger space to load sulfur and effectively capture polysulfides. The CS-CNTs@S cathode shows better electrochemical performance compared with CS-CPs@S and CS@S. The first discharge specific capacity is 1053 mAh g-1at 0.1 C. After 200 cycles, the specific capacity still remains at 427 mAh g-1.

20.
RNA Biol ; 18(sup1): 439-450, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34314293

RESUMO

RNA editing generates genetic diversity in mammals by altering amino acid sequences, miRNA targeting site sequences, influencing the stability of targeted RNAs, and causing changes in gene expression. However, the extent to which RNA editing affect gene expression via modifying miRNA binding site remains unexplored. Here, we first profiled the dynamic A-to-I RNA editome across tissues of Duroc and Luchuan pigs. The RNA editing events at the miRNA binding sites were generated. The biological function of the differentially edited gene in skeletal muscle was further characterized in pig muscle-derived satellite cells. RNA editome analysis revealed a total of 171,909 A-to-I RNA editing sites (RESs), and examination of its features showed that these A-to-I editing sites were mainly located in SINE retrotransposons PRE-1/Pre0_SS element. Analysis of differentially edited sites (DESs) revealed a total of 4,552 DESs across tissues between Duroc and Luchuan pigs, and functional category enrichment analysis of differentially edited gene (DEG) sets highlighted a significant association and enrichment of tissue-developmental pathways including TGF-beta, PI3K-Akt, AMPK, and Wnt signaling pathways. Moreover, we found that RNA editing events at the miRNA binding sites in the 3'-UTR of HSPA12B mRNA could prevent the miRNA-mediated mRNA downregulation of HSPA12B in the muscle-derived satellite (MDS) cell, consistent with the results obtained from the Luchuan skeletal muscle. This study represents the most systematic attempt to characterize the significance of RNA editing in regulating gene expression, particularly in skeletal muscle, constituting a new layer of regulation to understand the genetic mechanisms behind phenotype variance in animals.Abbreviations: A-to-I: Adenosine-to-inosine; ADAR: Adenosine deaminase acting on RNA; RES: RNA editing site; DEG: Differentially edited gene; DES: Differentially edited site; FDR: False discovery rate; GO: Gene Ontology; KEGG: Kyoto Encyclopaedia of Genes and Genomes; MDS cell: musclederived satellite cell; RPKM: Reads per kilobase of exon model in a gene per million mapped reads; UTR: Untranslated coding regions.


Assuntos
Regiões 3' não Traduzidas/genética , Regulação da Expressão Gênica , MicroRNAs/genética , Edição de RNA , RNA Mensageiro/genética , Retroelementos , Animais , MicroRNAs/metabolismo , Especificidade de Órgãos , RNA Mensageiro/metabolismo , Suínos
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