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1.
EMBO Rep ; 23(6): e53932, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35403787

RESUMO

Aberrant activation of stimulator of interferon genes (STING) is tightly associated with multiple types of disease, including cancer, infection, and autoimmune diseases. However, the development of STING modulators for the therapy of STING-related diseases is still an unmet clinical need. We employed a high-throughput screening approach based on the interaction of small-molecule chemical compounds with recombinant STING protein to identify functional STING modulators. Intriguingly, the cyclin-dependent protein kinase (CDK) inhibitor Palbociclib was found to directly bind STING and inhibit its activation in both mouse and human cells. Mechanistically, Palbociclib targets Y167 of STING to block its dimerization, its binding with cyclic dinucleotides, and its trafficking. Importantly, Palbociclib alleviates autoimmune disease features induced by dextran sulphate sodium or genetic ablation of three prime repair exonuclease 1 (Trex1) in mice in a STING-dependent manner. Our work identifies Palbociclib as a novel pharmacological inhibitor of STING that abrogates its homodimerization and provides a basis for the fast repurposing of this Food and Drug Administration-approved drug for the therapy of autoinflammatory diseases.


Assuntos
Doenças Autoimunes , Neoplasias , Animais , Doenças Autoimunes/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Neoplasias/metabolismo , Piperazinas/farmacologia , Piridinas/farmacologia , Piridinas/uso terapêutico
2.
Entropy (Basel) ; 26(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38248173

RESUMO

This paper introduces the notion of multi-sensitivity with respect to a vector within the context of non-autonomous dynamical systems on uniform spaces and provides insightful results regarding N-sensitivity and strongly multi-sensitivity, along with their behaviors under various conditions. The main results established are as follows: (1) For a k-periodic nonautonomous dynamical system on a Hausdorff uniform space (S,U), the system (S,fk∘⋯∘f1) exhibits N-sensitivity (or strongly multi-sensitivity) if and only if the system (S,f1,∞) displays N-sensitivity (or strongly multi-sensitivity). (2) Consider a finitely generated family of surjective maps on uniform space (S,U). If the system (S,f1,∞) is N-sensitive, then the system (S,fk,∞) is also N-sensitive. When the family f1,∞ is feebly open, the converse statement holds true as well. (3) Within a finitely generated family on uniform space (S,U), N-sensitivity (and strongly multi-sensitivity) persists under iteration. (4) We present a sufficient condition under which an nonautonomous dynamical system on infinite Hausdorff uniform space demonstrates N-sensitivity.

3.
Small ; 15(8): e1804947, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30690874

RESUMO

Semiconductor quantum dots (QDs) are among the most promising next-generation optoelectronic materials. QDs are generally obtained through either epitaxial or colloidal growth and carry the promise for solution-processed high-performance optoelectronic devices such as light-emitting diodes (LEDs), solar cells, etc. Herein, a straightforward approach to synthesize perovskite QDs and demonstrate their applications in efficient LEDs is reported. The perovskite QDs with controllable crystal sizes and properties are in situ synthesized through one-step spin-coating from perovskite precursor solutions followed by thermal annealing. These perovskite QDs feature size-dependent quantum confinement effect (with readily tunable emissions) and radiative monomolecular recombination. Despite the substantial structural inhomogeneity, the in situ generated perovskite QDs films emit narrow-bandwidth emission and high color stability due to efficient energy transfer between nanostructures that sweeps away the unfavorable disorder effects. Based on these materials, efficient LEDs with external quantum efficiencies up to 11.0% are realized. This makes the technologically appealing in situ approach promising for further development of state-of-the-art LED systems and other optoelectronic devices.

4.
Proteomics ; 18(15): e1700388, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29901268

RESUMO

Non-small cell lung cancer (NSCLC) patients carrying EGFR activating mutations treated with gefitinib, a tyrosine kinase inhibitor, will develop drug resistance. Ubiquitylation is one of major posttranslational modifications of proteins affecting the stability or function of proteins. However, the role of protein ubiquitylation in gefitinib resistance is poorly understood. To systematically identify the global change in protein expression and ubiquitylation during gefitinib resistance, a quantitative global proteome and ubiquitylome study in a pair of gefitinib-resistant and sensitive NSCLC cells is carried out. Altogether, changes in expression of 3773 proteins are quantified, and changes in ubiquitylation of 2893 lysine sites in 1415 proteins are measured in both cells. Interestingly, lysosomal and endocytic pathways, which are involved in autophagy regulation, are enriched with upregulated proteins or ubiquitylated proteins in gefitinib-resistant cells. In addition, HMGA2 overexpression or ALOX5 knockdown suppresses gefitinib resistance in NSCLC cells by inhibiting autophagy. Overall, these results reveal the previously unknown global ubiquitylome and proteomic features associated with gefitinib resistance, uncover the opposing roles of HMGA2 or ALOX5 in regulating gefitinib resistance and autophagy, and will help to identify new therapeutic targets in overcoming gefitinib resistance.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Resistencia a Medicamentos Antineoplásicos , Gefitinibe/farmacologia , Lisossomos/metabolismo , Proteoma/análise , Ubiquitina/metabolismo , Araquidonato 5-Lipoxigenase/química , Araquidonato 5-Lipoxigenase/genética , Araquidonato 5-Lipoxigenase/metabolismo , Autofagia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Endossomos/metabolismo , Ontologia Genética , Proteína HMGA2/genética , Proteína HMGA2/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Espectrometria de Massas , Inibidores de Proteínas Quinases/farmacologia , Processamento de Proteína Pós-Traducional , Proteoma/efeitos dos fármacos , Células Tumorais Cultivadas , Ubiquitinação
5.
J Biol Chem ; 291(5): 2087-106, 2016 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-26504080

RESUMO

Tumor invasiveness depends on the ability of tumor cells to breach endothelial barriers. In this study, we investigated the mechanism by which the adhesion of melanoma cells to endothelium regulates adherens junction integrity and modulates tumor transendothelial migration (TEM) by initiating thrombin generation. We found that the B-Raf(V600E) mutation in metastatic melanoma cells up-regulated tissue factor (TF) expression on cell membranes and promoted thrombin production. Co-culture of endothelial monolayers with metastatic melanoma cells mediated the opening of inter-endothelial spaces near melanoma cell contact sites in the presence of platelet-free plasma (PFP). By using small interfering RNA (siRNA), we demonstrated that B-Raf(V600E) and TF silencing attenuated the focal disassembly of adherens junction induced by tumor contact. Vascular endothelial-cadherin (VE-cadherin) disassembly was dependent on phosphorylation of p120-catenin on Ser-879 and VE-cadherin on Tyr-658, Tyr-685, and Tyr-731, which can be prevented by treatment with the thrombin inhibitor, hirudin, or by silencing the thrombin receptor, protease-activated receptor-1, in endothelial cells. We also provided strong evidence that tumor-derived thrombin enhanced melanoma TEM by inducing ubiquitination-coupled VE-cadherin internalization, focal adhesion formation, and actin assembly in endothelium. Confocal microscopic analysis of tumor TEM revealed that junctions transiently opened and resealed as tumor cells accomplished TEM. In addition, in the presence of PFP, tumor cells preferentially transmigrated via paracellular routes. PFP supported melanoma transmigration under shear conditions via a B-Raf(V600E)-thrombin-dependent mechanism. We concluded that the activation of thrombin generation by cancer cells in plasma is an important process regulating melanoma extravasation by disrupting endothelial junction integrity.


Assuntos
Endotélio Vascular/metabolismo , Melanoma/metabolismo , Proteínas Proto-Oncogênicas B-raf/metabolismo , Neoplasias Cutâneas/metabolismo , Trombina/metabolismo , Tromboplastina/metabolismo , Antígenos CD/metabolismo , Caderinas/metabolismo , Adesão Celular , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Movimento Celular , Impedância Elétrica , Inativação Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Mutação , Metástase Neoplásica , Permeabilidade , Fosforilação , Plasma/metabolismo , RNA Interferente Pequeno/metabolismo , Ubiquitinação
6.
Cell Physiol Biochem ; 31(1): 56-65, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23343715

RESUMO

BACKGROUND/AIMS: MicroRNAs (miRNAs) play important roles in tumorigenesis. We investigated the roles and mechanisms of miR-138 in human non-small cell lung cancer (NSCLC). METHODS: The expression of miR-138 was first examined in NSCLC cell lines and tumour tissues by real-time PCR The in vitro and in vivo functional effect of miR-138 was examined further. A luciferase reporter assay was conducted to confirm target association between miR-138 and the enhancer of zeste homolog 2 (EZH2). RESULTS: miR-138 was frequently downregulated in NSCLC cells and tissues. Overexpression of miR-138 inhibited proliferation of NSCLC cells in vitro and tumor growth in vivo. The EZH2 oncogene, which is often overexpressed in various human cancers and acts as an important regulator of cell growth and tumor invasion, was identified as a novel target of miR-138. miR-138 can bind to the 3' untranslated region (3' UTR) of EZH2 and suppress the expression of EZH2 at both mRNA and protein levels. Furthermore, knockdown of EZH2 phenocopied the tumor suppressive effects of miR-138 in cell models, whereas ectopic expression of EZH2 rescued the suppressive effects of miR-138. CONCLUSION: These findings define a tumor suppressor function for miR-138 in NSCLC and further suggest that miR-138 may represent a potential therapeutic target for NSCLC patients.


Assuntos
MicroRNAs/metabolismo , Complexo Repressor Polycomb 2/metabolismo , Regiões 3' não Traduzidas , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica , Regulação para Baixo , Proteína Potenciadora do Homólogo 2 de Zeste , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , MicroRNAs/genética , Complexo Repressor Polycomb 2/genética , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Transplante Heterólogo
7.
Front Endocrinol (Lausanne) ; 14: 1213465, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37876543

RESUMO

Objective: Hyperthyroidism in Chinese children is relatively high and has been increasing in recent years, which has a significant impact on their healthy development. Hyperthyroidism is a polygenic disorder that presents greater challenges in terms of prediction and treatment than monogenic diseases. This study aims to elucidate the associated functions and gene sets of mutated genes in children with hyperthyroidism in terms of the gene ontology through GO enrichment analysis and in terms of biological signaling pathways through KEGG enrichment analysis, thereby enhancing our understanding of the expected effects of multiple mutated genes on hyperthyroidism in children. Methods: Whole-exome sequencing was performed on the DNA samples of children with hyperthyroidism. Screening for pathogenic genes related to hyperthyroidism in affected children was performed using the publicly available disease databases Malacards, MutationView, and Clinvar, and the functions and influences of the identified pathogenic genes were analyzed using statistical analysis and the gene enrichment approach. Results: Through GO enrichment analysis, it was found that the most significant gene ontology enrichment was the function "hormone activity" in terms of gene ontology molecular function. The corresponding mutated genes set that has common effects on hyperthyroidism in children included TG, CALCA, POMC, CGA, PTH, GHRL, FBN1, TRH, PRL, LEP, ADIPOQ, INS, GH1. The second most significant gene ontology enrichment was the function "response to peptide hormone" in terms of biological process. The corresponding mutated genes set that has common effects on hyperthyroidism in children included LRP6, TSC2, KANK1, COL1A1, CDKN1B, POMC, STAT1, MEN1, APC, GHRL, TSHR, GJB2, FBN1, GPT, LEP, ADIPOQ, INS, GH1. Through KEGG enrichment analysis, it was found that the most significant biological signaling pathway enrichment was the pathway "Thyroid hormone signaling pathway" function. The corresponding mutated genes set that has common effects on hyperthyroidism in children included NOTCH3, MYH7, TSC2, STAT1, MED13L, MAP2K2, SLCO1C1, SLC16A2, and THRB. The second most significant biological signaling pathway enrichment was the pathway "Hypertrophic cardiomyopathy" in terms of biological process. The corresponding mutated genes set that has common effects on hyperthyroidism in children included IGF1, CACNA1S, MYH7, IL6, TTN, CACNB2, LAMA2, and DMD. Conclusion: The mutated genes in children with hyperthyroidism were closely linked to function involved in "hormone activity" and "response to peptide hormone" in terms of the biological signaling pathway, and to the functional pathways involved in "Thyroid hormone signaling pathway" and "Hypertrophic cardiomyopathy" in terms of the biological signaling pathway.


Assuntos
Cardiomiopatias , Hipertireoidismo , Transportadores de Ânions Orgânicos , Simportadores , Humanos , Criança , Biologia Computacional , Pró-Opiomelanocortina , Hipertireoidismo/genética , Hormônios Tireóideos , Proteínas do Citoesqueleto , Proteínas Adaptadoras de Transdução de Sinal , Transportadores de Ácidos Monocarboxílicos
8.
Front Bioeng Biotechnol ; 11: 1253048, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37771575

RESUMO

The treatment of breast cancer (BC) is a serious challenge due to its heterogeneous nature, multidrug resistance (MDR), and limited therapeutic options. Nanoparticle-based drug delivery systems (NDDSs) represent a promising tool for overcoming toxicity and chemotherapy drug resistance in BC treatment. No bibliometric studies have yet been published on the research landscape of NDDS-based treatment of BC. In this review, we extracted data from 1,752 articles on NDDS-based treatment of BC published between 2012 and 2022 from the Web of Science Core Collection (WOSCC) database. VOSviewer, CiteSpace, and some online platforms were used for bibliometric analysis and visualization. Publication trends were initially observed: in terms of geographical distribution, China and the United States had the most papers on this subject. The highest contributing institution was Sichuan University. In terms of authorship and co-cited authorship, the most prolific author was Yu Zhang. Furthermore, Qiang Zhang and co-workers have made tremendous achievements in the field of NDDS-based BC treatment. The article titled "Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications" had the most citations. The Journal of Controlled Release was one of the most active publishers in the field. "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries" was the most cited reference. We also analysed "hot" and cutting-edge research for NDDSs in BC treatment. There were nine topic clusters: "tumour microenvironment," "nanoparticles (drug delivery)," "breast cancer/triple-negative breast cancer," "combination therapy," "drug release (pathway)," "multidrug resistance," "recent advance," "targeted drug delivery", and "cancer nanomedicine." We also reviewed the core themes of research. In summary, this article reviewed the application of NDDSs in the treatment of BC.

9.
Adv Mater ; 35(8): e2209002, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36493461

RESUMO

Pure-red perovskite LEDs (PeLEDs) based on CsPb(Br/I)3 nanocrystals (NCs) usually suffer from a compromise in emission efficiency and spectral stability on account of the surface halide vacancies-induced nonradiative recombination loss, halide phase segregation, and self-doping effect. Herein, a "halide-equivalent" anion of benzenesulfonate (BS- ) is introduced into CsPb(Br/I)3 NCs as multifunctional additive to simultaneously address the above challenging issues. Joint experiment-theory characterizations reveal that the BS- can not only passivate the uncoordinated Pb2+ -related defects at the surface of NCs, but also increase the formation energy of halide vacancies. Moreover, because of the strong electron-withdrawing property of sulfonate group, electrons are expected to transfer from the CsPb(Br/I)3 NC to BS- for reducing the self-doping effect and altering the n-type behavior of CsPb(Br/I)3 NCs to near ambipolarity. Eventually, synergistic boost in device performance is achieved for pure-red PeLEDs with CIE coordinates of (0.70, 0.30) and a champion external quantum efficiency of 23.5%, which is one of the best value among the ever-reported red PeLEDs approaching to the Rec. 2020 red primary color. Moreover, the BS- -modified PeLED exhibits negligible wavelength shift under different operating voltages. This strategy paves an efficient way for improving the efficiency and stability of pure-red PeLEDs.

10.
Adv Mater ; 35(45): e2303938, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37464982

RESUMO

Achieving high-performance perovskite light-emitting diodes (PeLEDs) with pure-red electroluminescence for practical applications remains a critical challenge because of the problematic luminescence property and spectral instability of existing emitters. Herein, high-efficiency Rec. 2020 pure-red PeLEDs, simultaneously exhibiting exceptional brightness and spectral stability, based on CsPb(Br/I)3 perovskite nanocrystals (NCs) capping with aromatic amino acid ligands featuring cation-π interactions, are reported. It is proven that strong cation-π interactions between the PbI6 -octahedra of perovskite units and the electron-rich indole ring of tryptophan (TRP) molecules not only chemically polish the imperfect surface sites, but also markedly increase the binding affinity of the ligand molecules, leading to high photoluminescence quantum yields and greatly enhanced spectral stability of the CsPb(Br/I)3 NCs. Moreover, the incorporation of small-size aromatic TRP ligands ensures superior charge-transport properties of the assembled emissive layers. The resultant devices emitting at around 635 nm demonstrate a champion external quantum efficiency of 22.8%, a max luminance of 12 910 cd m-2 , and outstanding spectral stability, representing one of the best-performing Rec. 2020 pure-red PeLEDs achieved so far.

11.
Cancer Cell Int ; 12(1): 32, 2012 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-22720671

RESUMO

BACKGROUND: EPCs were isolated primarily in 1997 by Asahara et al. and recent studies indicated that bone-marrow-derived EPCs contributed little to the endothelium of tumor vessels. Tumors of the CNS system demonstrate various features of angiogenesis. METHODS: EPCs derived from rat bone marrow were isolated and cultured in M199 medium without any induced factors. EPCs were studied using immunohistochemical staining, Flow cytometry and culture under three-dimensional condition to determine EPCs' characteristics in vitro. We also established an animal model by injecting EPCs marked with Hoechst 33342 into the back of BALB/c nude mice and performed hematoxylin-eosin (HE) and immunofluorescent staining to study EPCs' features in vivo. To research effect of EPCs on glioma, animals bearing tumors model with C6 glioma were established. About 27 day after injection, we performed immunohistochemical staining and Immunofluorescence staining. RESULTS: Our results showed that EPCs derived from rat bone marrow appeared typical morphological characteristics and were positive of CD34, CD133, KDR and CD31 antigens at different time in vitro under the special M199 medium without any induced factors. The percentage of cells that expressed CD133 decreased gradually. In brief, the present study showed that EPCs derived from rat bone marrow differentiated into ECs in medium the without any induced factors and formed tubular structures in three-dimensional circumstances. Animal experiments suggested that EPCs differentiated into ECs and other else non-endothelial cells, and that EPCs contributed M199 of glioma. DISCUSSION: These findings provides some novel results about biological characteristics of EPCs in vivo and ex vivo, and an update on the effect of EPCs on glioma and which would be helpful for the overall understanding of EPCs and make EPCs to be implied on the clinical therapy.

12.
Mol Biol Rep ; 39(4): 3549-56, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21713404

RESUMO

Metastasis of tumor cells is associated with epithelial-to-mesenchymal transition (EMT), which is a process whereby epithelial cells lose their polarity and acquire new features of mesenchyme. EMT has been reported to be induced by transforming growth factor-ß1 (TGF-ß1), but its mechanism remains elusive. In this study, we performed a study to investigate whether PI3K/Akt and MAPK/Erk1/2 signaling pathways involved in EMT in the human lung cancer A549 cells. The results showed that after treated with TGF-ß1 for 48 h, A549 cells displayed more fibroblast-like shape, lost epithelial marker E-cadherin and increased mesenchymal markers Vimentin and Fibronectin. Moreover, TGF-ß1-induced EMT after 48 h was accompanied by increased of cell migration and change of Akt and Erk1/2 phosphorylation. In addition, EMT was reversed by PI3K inhibitor LY294002 and MEK1/2 inhibitor U0126, which suggested that A549 cells under stimulation of TGF-ß1 undergo a switch into mesenchymal cells and PI3K/Akt and MAPK/Erk1/2 signaling pathways serve to regulate TGF-ß1-induced EMT of A549 cells.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pulmonares/enzimologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Fibronectinas/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Fenótipo , Vimentina/metabolismo
13.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 29(6): 1073-7, 2012 Dec.
Artigo em Zh | MEDLINE | ID: mdl-23469533

RESUMO

The present paper was aimed to study the relationship between the pneumonia clinical features and the pathogens of pneumonia in children by making use of association rules based on the clinical data of 6 300 cases of pneumonia. Through software analysis, the different association relationship can be obtained between different clinical features of pneumonia in children, such as gender, age and region, etc., and the pathogens of pneumonia. For example, children of different sex with the same pathogen showed different association relationships. Due to the different association relationships between the pneumonia clinical features and the pathogens of pneumonia in children of Guangzhou area, different methods in prevention and treatment of children's pneumonia should be adopted according to actual condition, in order to achieve the best results.


Assuntos
Pneumonia/microbiologia , Adolescente , Fatores Etários , Broncopneumonia/epidemiologia , Broncopneumonia/microbiologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Incidência , Lactente , Masculino , Pneumonia/epidemiologia , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/microbiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/microbiologia , Fatores Sexuais , Software
14.
J Environ Public Health ; 2022: 4064135, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35685862

RESUMO

Environmental problem is an international problem that transcends national boundaries and develops into regional and global environmental pollution and ecological problems. Facing the increasing environmental pollution, the international community has successively formulated many relevant environmental pollution prevention laws, but the world situation is complicated after all, environmental problems still emerge endlessly, and the protection of environmental rights has become the consensus of the international community. Environmental right is an integral part of human rights, and protecting environmental right is the concrete expression and proper meaning of protecting human rights. Using international criminal law to protect environmental rights will play a positive role in global environmental protection. As with the development of computer technology, the research of machine learning has gradually transferred to the field of social science, especially the judicial field. While sentencing is a crucial part of environmental crime, this paper studies the sentencing of environmental rights cases from the perspective of international criminal law and uses Convolutional Neural Networks (CNN) to determine the sentencing of environmental rights cases. Through the experiment on the Integrated Database (IDB) dataset, the results show that the introduction of CNN improves the effect of the sentencing term prediction model and the fine prediction model significantly. The CNN-based model scored 91.6542 in the sentencing term prediction model and 90.8890 in the fine prediction model.


Assuntos
Inteligência Artificial , Direito Penal , Humanos
15.
Mol Cell Biochem ; 355(1-2): 309-14, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21695462

RESUMO

Lung cancer is a highly malignant carcinoma, and most deaths of lung cancer are caused by metastasis. The alterations associated with epithelial-to-mesenchymal transition (EMT) may be related to the cancer cell metastasis. Nevertheless, the mechanism of lung cancer metastasis remains unclear. We conducted a study in vitro to investigate whether transforming growth factor-ß1 (TGF-ß1) could induce changes of, such as cell morphology, expression of relative protein markers, and cellular motile and invasive activities. In this research, the changes of cell morphology were first investigated under a phase contrast microscope, then western blotting was employed to detect the expression of E-cadherin, vimentin, and fibronectin, and finally cell motility and invasion were evaluated by cell wound-healing as well as invasion assays. The data indicated that human lung adenocarcinoma cell lines, A-549 and PC-9 cells of epithelial cell characteristics, were induced to undergo EMT by TGF-ß1. Following TGF-ß1 treatment, cells showed dramatic morphological changes assessed by phase contrast microscopy, accompanied by decreased epithelial marker E-cadherin and increased mesenchymal markers vimentin and fibronectin. More importantly, cell motility and invasion were also enhanced in the EMT process. These results indicated that TGF-ß1 may promote lung adenocarcinoma invasion and metastasis via the mechanism of EMT.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Adenocarcinoma , Caderinas/metabolismo , Linhagem Celular Tumoral , Ensaios de Migração Celular , Movimento Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Fibronectinas/metabolismo , Humanos , Neoplasias Pulmonares , Invasividade Neoplásica , Metástase Neoplásica , Fator de Crescimento Transformador beta1/fisiologia , Vimentina/metabolismo
16.
Zhonghua Zhong Liu Za Zhi ; 33(8): 590-3, 2011 Aug.
Artigo em Zh | MEDLINE | ID: mdl-22325218

RESUMO

OBJECTIVE: To investigate the effect of epithelial-mesenchymal transition (EMT) on the expression of microRNAs (miRNAs) in lung cancer A549 cells. METHODS: Transforming growth factor beta-1 (TGF-beta 1) in different concentrations was used to induce EMT in lung cancer A549 cells. The morphological changes were observed under phase-contrast microscope. The changes of EMT-related proteins were analyzed by Western blot. The changes of miRNAs expression after EMT were detected by microRNA (miRNA) array. Real time quantitative RT-PCR was applied to verify the reliability of miRNA array results. RESULTS: The lung cancer A549 cells became elongated and the cell-cell junction became loose after EMT. The epithelial protein marker E-cadherin was down-regulated and the mesenchymal protein markers vimentin and fibronectin up-regulated. There were 51 miRNAs showing statistically significant changes of expression more than double (P<0.05) after EMT. Among them 18 were up-regulated and 33 down-regulated. Of them, mir-33a was down-regulated by 92.8% and mir-193a-3p by 86.5%. Real time quantitative RT-PCR showed that mir-33a was down-regulated by 73.1% and mir-193a-3p by 56.6%. CONCLUSION: Epithelial-mesenchymal transition has effects on the expression of miRNAs, and miRNAs may regulate the invasion and metastasis of lung cancer cells via EMT.


Assuntos
Adenocarcinoma/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Caderinas/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibronectinas/metabolismo , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Fator de Crescimento Transformador beta1/administração & dosagem , Fator de Crescimento Transformador beta1/farmacologia , Vimentina/metabolismo
17.
Adv Mater ; 33(49): e2104381, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34632623

RESUMO

Perovskite light-emitting diodes (PeLEDs) have recently shown significant progress with external quantum efficiencies (EQEs) exceeding 20%. However, PeLEDs with pure-red (620-660 nm) light emission, an essential part for full-color displays, remain a great challenge. Herein, a general approach of spacer cation alloying is employed in Ruddlesden-Popper perovskites (RPPs) for efficient red PeLEDs with precisely tunable wavelengths. By simply tuning the alloying ratio of dual spacer cations, the thickness distribution of quantum wells in the RPP films can be precisely modulated without deteriorating their charge-transport ability and energy funneling processes. Consequently, efficient PeLEDs with tunable emissions between pure red (626 nm) and deep red (671 nm) are achieved with peak EQEs up to 11.5%, representing the highest values among RPP-based pure-red PeLEDs. This work opens a new route for color tuning, which will spur future developments of pure-red or even pure-blue PeLEDs with high performance.

18.
Aging (Albany NY) ; 13(8): 11381-11410, 2021 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-33839701

RESUMO

Interferon-gamma (IFN-γ) plays a complex role in modulating tumor microenvironment during lung adenocarcinoma (LUAD) development. In order to define the role of IFN-γ response genes in LUAD progression, we characterized the gene expression, mutation profile, protein-protein interaction of 24 IFN-γ response genes, which exhibited significant hazard ratio in overall survival. Two subgroups of LUAD from the TCGA cohort, which showed significant difference in the survival rate, were identified based on the expression of these genes. Furthermore, LASSO penalized cox regression model was used to derive a risk signature comprising seven IFN-γ response genes, including CD74, CSF2RB, PTPN6, MT2A, NMI, LATS2, and PFKP, which can serve as an independent prognostic predictor of LUAD. The risk signature was validated in an independent LUAD cohort. The high risk group is enriched with genes regulating cell cycle and DNA replication, as well as a high level of pro-tumor immune cells. In addition, the risk score is negatively correlated with the expression of immune metagenes, but positively correlated with DNA damage repair genes. Our findings reveal that seven-gene risk signature can be a valuable prognostic predictor for LUAD, and they are crucial participants in tumor microenvironment of LUAD.


Assuntos
Adenocarcinoma de Pulmão/mortalidade , Biomarcadores Tumorais/genética , Interferon gama/metabolismo , Neoplasias Pulmonares/mortalidade , Microambiente Tumoral/imunologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Biologia Computacional , Reparo do DNA/imunologia , Conjuntos de Dados como Assunto , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Estimativa de Kaplan-Meier , Pulmão/imunologia , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco/métodos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Taxa de Sobrevida , Transcriptoma/imunologia
19.
J Phys Chem Lett ; 12(26): 6041-6047, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34165316

RESUMO

Bandgap tuning through mixing halide anions is one of the most attractive features for metal halide perovskites. However, mixed halide perovskites usually suffer from phase segregation under electrical biases. Herein, we obtain high-performance and color-stable blue perovskite LEDs (PeLEDs) based on mixed bromide/chloride three-dimensional (3D) structures. We demonstrate that the color instability of CsPb(Br1-xClx)3 PeLEDs results from surface defects at perovskite grain boundaries. By effective defect passivation, we achieve color-stable blue electroluminescence from CsPb(Br1-xClx)3 PeLEDs, with maximum external quantum efficiencies of up to 4.5% and high luminance of up to 5351 cd m-2 in the sky-blue region (489 nm). Our work provides new insights into the color instability issue of mixed halide perovskites and can spur new development of high-performance and color-stable blue PeLEDs.

20.
J Phys Chem Lett ; 12(25): 5836-5843, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34138577

RESUMO

Amines are widely employed as additives for improving the performance of metal halide perovskite optoelectronic devices. However, amines are well-known for their high chemical reactivity, the impact of which has yet to receive enough attention from the perovskite light-emitting diode community. Here, by investigating an unusual positive aging effect of CH3NH3I/CsI/PbI2 precursor solutions as an example, we reveal that amines gradually undergo N-formylation in perovskite precursors over time. This reaction is initialized by hydrolysis of dimethylformamide in the acidic chemical environment. Further investigations suggest that the reaction products collectively impact perovskite crystallization and eventually lead to significantly enhanced external quantum efficiency values, increasing from ∼2% for fresh solutions to ≳12% for aged ones. While this case study provides a positive aging effect, a negative aging effect is possible in other perovksite systems. Our findings pave the way for more reliable and reproducible device fabrication and call for further attention to underlying chemical reactions within the perovskite inks once amine additives are included.

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