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1.
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.

2.
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
3.
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.

4.
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.

5.
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.

6.
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
7.
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
8.
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.

9.
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.

10.
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.

11.
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
12.
ACS Appl Mater Interfaces ; 12(22): 24965-24970, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32394700

RESUMO

Quasi-two-dimensional (Q-2D) perovskites featured with multidimensional quantum wells (QWs) have been the main candidates for optoelectronic applications. However, excessive low-dimensional perovskites are unfavorable to the device efficiency due to the phonon-exciton interaction and the inclusion of insulating large organic cations. Herein, the formation of low-dimensional QWs is suppressed by removing the organic cation 1-naphthylmethylamine iodide (NMAI) through ultrahigh vacuum (UHV) annealing. Perovskite light-emitting diode (PLED) devices based on films annealed with optimized UHV conditions show a higher external quantum efficiency (EQE) of 13.0% and wall-plug efficiency of 11.1% compared to otherwise identical devices with films annealed in a glovebox.

13.
Nat Commun ; 11(1): 891, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060279

RESUMO

Although perovskite light-emitting diodes (PeLEDs) have recently experienced significant progress, there are only scattered reports of PeLEDs with both high efficiency and long operational stability, calling for additional strategies to address this challenge. Here, we develop perovskite-molecule composite thin films for efficient and stable PeLEDs. The perovskite-molecule composite thin films consist of in-situ formed high-quality perovskite nanocrystals embedded in the electron-transport molecular matrix, which controls nucleation process of perovskites, leading to PeLEDs with a peak external quantum efficiency of 17.3% and half-lifetime of approximately 100 h. In addition, we find that the device degradation mechanism at high driving voltages is different from that at low driving voltages. This work provides an effective strategy and deep understanding for achieving efficient and stable PeLEDs from both material and device perspectives.

14.
Chem Sci ; 11(41): 11338-11343, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34094376

RESUMO

Metal halide perovskites have demonstrated impressive properties for achieving efficient monochromatic light-emitting diodes. However, the development of white perovskite light-emitting diodes (PeLEDs) remains a big challenge. Here, we demonstrate a single-emissive-layer all-perovskite white PeLED using a mixed halide perovskite film as the emissive layer. The perovskite film consists of separated mixed halide perovskite phases with blue and red emissions, which are beneficial for suppressing halide anion exchange and preventing charge transfer. As a result, the white PeLED shows balanced white light emission with Commission Internationale de L'Eclairage coordinates of (0.33, 0.33). In addition, we find that the achievement of white light emission from mixed halide perovskites strongly depends on effective modulation of the halide salt precursors, especially lead bromide and benzamidine hydrochloride in our case. Our work provides very useful guidelines for realizing single-emissive-layer all-perovskite white PeLEDs based on mixed halide perovskites, which will spur the development of high-performance white PeLEDs.

15.
Adv Mater ; 31(41): e1904243, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31456250

RESUMO

Ruddlesden-Popper perovskites (RPPs), consisting of alternating organic spacer layers and inorganic layers, have emerged as a promising alternative to 3D perovskites for both photovoltaic and light-emitting applications. The organic spacer layers provide a wide range of new possibilities to tune the properties and even provide new functionalities for RPPs. However, the preparation of state-of-the-art RPPs requires organic ammonium halides as the starting materials, which need to be ex situ synthesized. A novel approach to prepare high-quality RPP films through in situ formation of organic spacer cations from amines is presented. Compared with control devices fabricated from organic ammonium halides, this new approach results in similar (and even better) device performance for both solar cells and light-emitting diodes. High-quality RPP films are fabricated based on different types of amines, demonstrating the universality of the approach. This approach not only represents a new pathway to fabricate efficient devices based on RPPs, but also provides an effective method to screen new organic spacers with further improved performance.

16.
Oncol Rep ; 41(3): 1817-1826, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30628703

RESUMO

The cancer stem cell theory recently has received enormous attention in cancer biology. Lung cancer stem­like cells are a subpopulation of undifferentiated lung tumor cells critical for lung cancer tumorigenesis, metastasis and resistance to therapy and disease relapse. The neural EGFL like 1 (NELL1) is a potent growth factor believed to preferentially target cells committed to the osteochondral lineage; yet, its expression and function in lung cancer are largely unknown. In the present study, we used specific medium to accumulate lung cancer stem­like cells of 95­D cells in spheres and obtained these highly expressed CD133 cells through flow cytometric cell sorting of CD133­stained cells which were termed 95­D lung cancer stem­like cells (95­D LCSCs). These 95­D LCSCs highly expressed stemness genes CD133, Oct4 and Sox2 determined by western blot analysis and quantitative real­time polymerase chain reaction (qPCR) analysis. Notably, we found that overexpression of NELL1 significantly reduced colony formation and invasion of 95­D LCSCs tested by soft agar colony formation and cell invasion assay. In addition, as determined by cell proliferation assay, overexpression of NELL1 increased the chemotherapeutic sensitivity of 95­D LCSCs to carboplatin and cisplatin. NELL1 also reduced the expression of phospho­MET (p­MET), Notch3 and HES1, which suggests that NELL1 may induce 95­D LCSC differentiation by inhibiting the expression of c­MET­Notch signaling. Our results suggest that NELL1 induces lung cancer stem­like cell differentiation, which provides a new potential therapeutic target for cancer stem cells.


Assuntos
Diferenciação Celular , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/patologia , Proteínas do Tecido Nervoso/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas de Ligação ao Cálcio , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Separação Celular , Resistencia a Medicamentos Antineoplásicos , Citometria de Fluxo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais
17.
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.

18.
Cell Death Dis ; 9(10): 989, 2018 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-30250191

RESUMO

IL-2 is critical to the activation, growth, and survival of T cells and NK cells, and maintains the delicate balance between auto-immunity and anti-neoplasm surveillance. High IL-2 doses have clear antitumor capabilities, but also have severe side effects that limit its clinical use. Side effects include the vascular leak syndrome (VLS), which results in lung edema and liver damage. Therefore, a new version of IL-2 that does not induce organ toxicity would improve IL-2-based immunotherapy. We conducted a systematic screening by changing one amino acid at a time at the interaction area of IL-2 with its receptor IL-2R to select one particular mutant IL-2, FSD13, in which the proline at position 65 was substituted by lysine (P65L). FSD13 had a greater ability than wild-type IL-2 in stimulating CD4+ T, CD8+ T, and NK cell proliferation, enhancing the expression of CD69, CD183, CD44, and CD54 in these cells, and triggering cancer cell apoptosis. FSD13 had three-time lower than wild-type IL-2 in inducing CD4+ T to Tregs. Compared with wild-type IL-2, FSD13 greatly limited the growth, invasion into adjacent tissues, and metastasis of melanoma metastatic into the lung. In contrast to wild-type IL-2, high dose of FSD3 did not alter structures and induce any pathogenic changes in the liver and lung. Thus, we generated a novel the IL-2 mutant, FSD13, by targeting a different area than previously reported. FSD13 surpasses the wild-type IL-2's ability in stimulating the antitumor immune cell functions, but exerts much less systemic toxicity.


Assuntos
Antineoplásicos/efeitos adversos , Descoberta de Drogas/métodos , Imunoterapia , Interleucina-2/uso terapêutico , Neoplasias Pulmonares/terapia , Melanoma Experimental/terapia , Substituição de Aminoácidos , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Modelos Animais de Doenças , Humanos , Interleucina-2/efeitos adversos , Interleucina-2/genética , Células K562 , Células Matadoras Naturais/metabolismo , Neoplasias Pulmonares/patologia , Ativação Linfocitária/efeitos dos fármacos , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Resultado do Tratamento
19.
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
20.
J Mater Chem C Mater ; 6(26): 6996-7002, 2018 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-30713691

RESUMO

To achieve high-performance perovskite light-emitting diodes (PeLEDs), an appropriate functional layer beneath the perovskite emissive layer is significantly important to modulate the morphology of the perovskite film and to facilitate charge injection and transport in the device. Herein, for the first time, we report efficient n-i-p structured PeLEDs using solution-processed SnO2 as an electron transport layer. Three-dimensional perovskites, such as CH(NH2)2PbI3 and CH3NH3PbI3, are found to be more chemically compatible with SnO2 than with commonly used ZnO. In addition, SnO2 shows good transparency, excellent morphology and suitable energy levels. These properties make SnO2 a promising candidate in both three- and low-dimensional PeLEDs, among which a high external quantum efficiency of 7.9% has been realized. Furthermore, interfacial materials that are widely used to improve the device performances of ZnO-based PeLEDs are also applied on SnO2-based PeLEDs and their effects have been systematically studied. In contrast to ZnO, SnO2 modified by these interfacial materials shows detrimental effects due to photoluminescence quenching.

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