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1.
J Ethnopharmacol ; 328: 118058, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38513778

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Baoyuan Decoction (BYD) was initially recorded in the classic of "Bo Ai Xin Jian" in the Ming dynasty. It is traditionally used for treating weakness and cowardice, and deficiency of vital energy. In researches related to anti-fatigue effects, the reciprocal regulation of AMPK and circadian clocks likely plays an important role in anti-fatigue mechanism, while it has not yet been revealed. Therefore, we elucidated the anti-fatigue mechanism of BYD through AMPK/CRY2/PER1 pathway. AIM OF THE STUDY: To investigate the effect and mechanism of BYD in reducing fatigue, using pharmacodynamics, network pharmacology and transcriptomics through the AMPK/CRY2/PER1 signaling pathway. MATERIALS AND METHODS: Firstly, the chemical constituents of BYD were qualitatively identified by UHPLC-Q-Exactive Orbitrap/MS, establishing a comprehensive strategy with an in-house library, Xcalibur software and Pubchem combined. Secondly, a Na2SO3-induced fatigue model and 2,2'-Azobis (2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress model were developed to evaluate the anti-fatigue and anti-oxidant activities of BYD using AB zebrafish. The anti-inflammatory activity of BYD was evaluated using CuSO4-induced and tail cutting-induced Tg (lyz: dsRed) transgenic zebrafish inflammation models. Then, target screening was performed by Swiss ADME, GeneCards, OMIM and DrugBank databases, the network was constructed using Cytoscape 3.9.0. Transcriptome and network pharmacology technology were used to investigate the related signaling pathways and potential mechanisms after treatment with BYD, which were verified by real-time quantitative PCR (RT-qPCR). RESULTS: In total, 114 compounds from the water extract of BYD were identified as major compounds. Na2SO3-induced fatigue model and AAPH-induced oxidative stress model indicated that BYD has significant anti-fatigue and antioxidant effects. Meanwhile, BYD showed significant anti-inflammatory effects on CuSO4-induced and tail cutting-induced zebrafish inflammation models. The KEGG result of network pharmacology showed that the anti-fatigue function of BYD was mainly effected through AMPK signaling pathway. Besides, transcriptome analysis indicated that the circadian rhythm, AMPK and IL-17 signaling pathways were recommended as the main pathways related to the anti-fatigue effect of BYD. The RT-qPCR results showed that compared with a model control group, the treatment of BYD significantly elevated the expression mRNA of AMPK, CRY2 and PER1. CONCLUSION: Herein, we identified 114 chemical constituents of BYD, performed zebrafish activity validation, while demonstrated that BYD can relieve fatigue by AMPK/CRY2/PER1 signaling pathway through network pharmacology and transcriptome.


Assuntos
Proteínas Quinases Ativadas por AMP , Amidinas , Medicamentos de Ervas Chinesas , Animais , Peixe-Zebra , Estresse Oxidativo , Fadiga/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/tratamento farmacológico , Antioxidantes , Transdução de Sinais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
2.
Nat Prod Bioprospect ; 14(1): 18, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38421454

RESUMO

The aberrant activation of the Wnt/ß-catenin signaling pathway is closely associated with the development of various carcinomas, especially colorectal cancers (CRCs), where adenomatous colorectal polyposis (APC) mutations are the most frequently observed, which limits the anti-tumor efficiency of inhibitors targeting the upstream of Wnt/ß-catenin pathway. The anti-tumor activity of the naturally occurring alkaloid cepharanthine (CEP) extracted from the plant Stephania cepharantha Hayata has been reported in various types of tumors. We previously observed that its derivatives inhibited the Wnt/ß-catenin signaling in liver cancer; however, the specific mechanism remains unknown. In this study, we confirmed CEP can effectively inhibit APC-mutant CRC cell lines (SW480, SW620, LoVo) through disturbing of the Wnt/ß-catenin signaling and elucidated the underlying mechanisms. Here, we demonstrate that CEP attenuates the Wnt/ß-catenin signaling by decreasing the ß-catenin, subsequently impeding the proliferation of APC-mutant CRCs. Moreover, CEP induced ß-catenin transcription inhibition rather than the instability of ß-catenin protein and mRNA contributes to reduction of ß-catenin. Taken together, our findings identify CEP as the first ß-catenin transcriptional inhibitor in the modulation of Wnt/ß-catenin signaling and indicate CEP as a potential therapeutic option for the treatment of APC-mutated CRCs.

3.
Nat Prod Bioprospect ; 14(1): 3, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38169019

RESUMO

Phosphoinositide 3-kinase (PI3Ks) are lipid kinases widely involved in cell proliferation, metastasis and differentiation. Constitutive activation of the PI3K/Akt/mTOR signaling are well confirmed in colorectal cancers (CRCs). In this study, we identified isopropyl 9-ethyl-1-(naphthalen-1-yl)-9 H-pyrido[3,4-b] indole-3-carboxylate (Z86), as a novel PI3Kα inhibitor with the IC50 value of 4.28 µM. The binding of Z86 to PI3Kα was further confirmed with DARTS and CETSA assay. Immunofluorescence analysis and western blotting data demonstrated that Z86 effectively attenuated PI3K/AKT pathway. Z86 caused dramatic proliferation inhibition of CRCs through G0/G1 cycle arrest rather than apoptosis induction. Besides, the migration of CRCs was also relieved by Z86. The present study not only identified Z86 as a novel PI3Kα inhibitor with potent inhibitory efficiency on PI3K-mediated CRCs growth and migration, but also elucidated a reasonable molecular mechanism of Z86 in the Wnt signaling pathway inhibition.

4.
Nature ; 622(7983): 493-498, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37557914

RESUMO

Lead halide perovskite light-emitting diodes (PeLEDs) have demonstrated remarkable optoelectronic performance1-3. However, there are potential toxicity issues with lead4,5 and removing lead from the best-performing PeLEDs-without compromising their high external quantum efficiencies-remains a challenge. Here we report a tautomeric-mixture-coordination-induced electron localization strategy to stabilize the lead-free tin perovskite TEA2SnI4 (TEAI is 2-thiopheneethylammonium iodide) by incorporating cyanuric acid. We demonstrate that a crucial function of the coordination is to amplify the electronic effects, even for those Sn atoms that aren't strongly bonded with cyanuric acid owing to the formation of hydrogen-bonded tautomeric dimer and trimer superstructures on the perovskite surface. This electron localization weakens adverse effects from Anderson localization and improves ordering in the crystal structure of TEA2SnI4. These factors result in a two-orders-of-magnitude reduction in the non-radiative recombination capture coefficient and an approximately twofold enhancement in the exciton binding energy. Our lead-free PeLED has an external quantum efficiency of up to 20.29%, representing a performance comparable to that of state-of-the-art lead-containing PeLEDs6-12. We anticipate that these findings will provide insights into the stabilization of Sn(II) perovskites and further the development of lead-free perovskite applications.

5.
Front Chem ; 11: 1191498, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37234201

RESUMO

Three series of podophyllotoxin derivatives with various nitrogen-containing heterocycles were designed and synthesized. The antitumor activity of these podophyllotoxin derivatives was evaluated in vitro against a panel of human tumor cell lines. The results showed that podophyllotoxin-imidazolium salts and podophyllotoxin-1,2,4-triazolium salts a1-a20 exhibited excellent cytotoxic activity. Among them, a6 was the most potent cytotoxic compound with IC50 values of 0.04-0.29 µM. Podophyllotoxin-1,2,3-triazole derivatives b1-b5 displayed medium cytotoxic activity, and podophyllotoxin-amine compounds c1-c3 has good cytotoxic activity with IC50 value of 0.04-0.58 µM. Furthermore, cell cycle and apoptosis experiments of compound a6 were carried out and the results exhibited that a6 could induce G2/M cell cycle arrest and apoptosis in HCT-116 cells.

6.
Biochem Biophys Res Commun ; 659: 10-19, 2023 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-37030020

RESUMO

The activating receptor natural killer group 2D (NKG2D) expressed by Natural killer (NK) cells functions as a "master-switch" in governing the awakening status of NK cells. The NKG2D-mediated cytotoxicity has been declared to be related with the expression levels of NKG2D ligands (NKG2DLs) expressed on tumor cells. Therefore, selective induction of NKG2DLs could be a reliable approach to enhance the efficacy of NK cell-mediated immunotherapy. Our existing study demonstrated that Ciclopirox Olamine (CPX), an off-patent antifungal agent, effectively elevated the expression of NKG2DLs on leukemia cells and sensitized leukemia cells to NK-cell mediated cytolysis. Induction of ROS production and AKT phosphorylation by CPX is essential for the up-regulation of NKG2DLs expressions. Inhibition of AKT by using AKT inhibitor MK2206 decreased both NKG2DLs expressions and NK cell cytotoxicity. These data indicated that increased sensitivity of CPX-treated leukemia cells to NK cell cytolysis was attributed to higher NKG2DLs expressions, resulting from activated AKT signaling pathway. Our findings support the ongoing development of CPX as an anti-tumor agent and suggest its promising immunotherapeutic value in the medication of leukemia.


Assuntos
Leucemia , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ciclopirox/farmacologia , Ciclopirox/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Células Matadoras Naturais/metabolismo , Transdução de Sinais , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Linhagem Celular Tumoral
7.
Eur J Pharmacol ; 945: 175628, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36858339

RESUMO

Wnt/ß-catenin signaling pathway is a classical and crucial oncogenic pathway in many carcinomas, and Porcupine (PORCN) is an O-acyltransferase, which is indispensable and highly specific for catalyzing palmitoylation of Wnt ligands and facilitating their secretion and biofunction. Targeting PORCN provides a promising approach to specifically cure Wnt-driven cancers from the root. In this study, we designed series of pyridonyl acetamide compounds, and discovered a novel PORCN inhibitor WHN-88 with a unique di-iodinated pyridone structural fragment, which is significantly different from the reported inhibitors. We demonstrated that WHN-88 effectively abolished palmitoylation of Wnt ligands and prevented their secretion and the subsequent Wnt/ß-catenin signaling transduction. Further experiments showed that, at well-tolerated doses, WHN-88 remarkably suppressed the spontaneous occurrence and growth of MMTV-Wnt1 murine breast tumors. Consistently, WHN-88 also notably restrained the progress of xenografted Wnt-driven human tumors, including PA-1 teratocarcinoma with high autocrine Wnt signaling and Aspc-1 pancreatic carcinoma with Wnt-sensitizing RNF43 mutation. Additionally, we disclosed that WHN-88 inhibited cancer cell stemness obviously. Together, we verified WHN-88 is a novel PORCN inhibitor with potent efficacy against the Wnt-driven cancers. Our findings enriched the structural types of PORCN inhibitors, and facilitated the development and application of PORCN inhibiting therapy in clinic.


Assuntos
Neoplasias Pancreáticas , Via de Sinalização Wnt , Animais , Humanos , Camundongos , Aciltransferases/química , Aciltransferases/genética , Aciltransferases/metabolismo , beta Catenina/metabolismo , Ligantes , Proteínas de Membrana/metabolismo , Mutação
8.
Front Neurol ; 14: 1089067, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937532

RESUMO

Aims: Depression in bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), leading to mistreatments and poor clinical outcomes in many bipolar patients. Herein, we report direct comparisons between medication-free patients with BD and those with UD in terms of the microstructure and neurometabolites in eight brain regions. Methods: A total of 20 patients with BD, 30 with UD patients, and 20 matched healthy controls (HCs) underwent 3.0T magnetic resonance imaging with chemical exchange saturation transfer (CEST) for glutamate (Glu; GluCEST) imaging, multivoxel magnetic resonance spectroscopy, and diffusion kurtosis imaging. Results: Compared with HCs, patients with UD showed significantly lower levels of multiple metabolites, GluCEST% values, and diffusional kurtosis [mean kurtosis (MK)] values in most brain regions. In contrast, patients with BD presented significantly higher levels of Glu in their bilateral ventral prefrontal white matter (VPFWM), higher choline (Cho)-containing compounds in their left VPFWM and anterior cingulate cortex (ACC), and higher GluCEST% values in their bilateral VPFWM and ACC; moreover, reduced MK in these patients was more prominent in the left VPFWM and left thalamus. Conclusion: The findings demonstrated that both patients with UD and BD have abnormal microstructure and metabolic alterations, and the changes are not completely consistent in the prefrontal lobe region. Elevated Glu, Cho, and GluCEST% in the ACC and VPFWM of patients with UD and BD may help in differentiating between these two disorders. Our findings support the significance for the microstructural integrity and brain metabolic changes of the prefrontal lobe region in BD and UD.

9.
Chem Soc Rev ; 52(4): 1519, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36756836

RESUMO

Correction for 'Atomically flat semiconductor nanoplatelets for light-emitting applications' by Bing Bai et al., Chem. Soc. Rev., 2023, 52, 318-360, https://doi.org/10.1039/D2CS00130F.

10.
Small ; 19(16): e2207260, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36651021

RESUMO

Solution-processed perovskite-based light-emitting diodes (PeLEDs) are promising candidates for low-cost, large-area displays, while severe deterioration of the perovskite light-emitting layer occurs during deposition of electron transport layers from solution in an issue. Herein, core/shell ZnO/ZnS nanoparticles as a solution-processed electron transport layer in PeLED based on quasi-2D PEA2 Csn-1 Pbn Br3n+1 (PEA = phenylethylammonium) perovskite are employed. The deposition of ZnS shell mitigates trap states on ZnO core by anchoring sulfur to oxygen vacancies, and at the same time removes residual hydroxyl groups, which helps to suppress the interfacial trap-assisted non-radiative recombination and the deprotonation reaction between the perovskite layer and ZnO. The core/shell ZnO/ZnS nanoparticles show comparably high electron mobility to pristine ZnO nanoparticles, combined with the reduced energy barrier between the electron transport layer and the perovskite layer, improving the charge injection balance in PeLEDs. As a result, the optimized PeLEDs employing core/shell ZnO/ZnS nanoparticles as a solution-processed electron transport layer exhibit high peak luminance reaching 32 400 cd m-2 , external quantum efficiency of 10.3%, and 20-fold extended longevity as compared to the devices utilizing ZnO nanoparticles, which represents one of the highest overall performances for solution-processed PeLEDs.

11.
Nano Lett ; 23(3): 985-992, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36715576

RESUMO

Despite the rapid progress in perovskite light-emitting diodes (PeLEDs), the electroluminescence performance of large-area perovskite devices lags far behind that of laboratory-size ones. Here, we report a 3.5 cm × 3.5 cm large-area PeLED with a record-high external quantum efficiency of 12.1% by creating an amphipathic molecular interface modifier of betaine citrate (BC) between the perovskite layer and the underlying hole transport layer (HTL). It is found that the surface wettability for various HTLs can be efficiently improved as a result of the coexistence of methyl and carboxyl groups in the BC molecules that makes favorable groups to selectively contact with the HTL surface and increases the surface free energy, which greatly facilitates the scalable process of solution-processed perovskite films. Moreover, the luminous performance of perovskite emitters is simultaneously enhanced through the coordination between C═O in the carboxyl groups and Pb dangling bonds.

12.
Chem Soc Rev ; 52(1): 318-360, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36533300

RESUMO

The last decade has witnessed extensive breakthroughs and significant progress in atomically flat two-dimensional (2D) semiconductor nanoplatelets (NPLs) in terms of synthesis, growth mechanisms, optical and electronic properties and practical applications. Such NPLs have electronic structures similar to those of quantum wells in which excitons are predominantly confined along the vertical direction, while electrons are free to move in the lateral directions, resulting in unique optical properties, such as extremely narrow emission line width, short photoluminescence (PL) lifetime, high gain coefficient, and giant oscillator strength transition (GOST). These unique optical properties make NPLs favorable for high color purity light-emitting applications, in particular in light-emitting diodes (LEDs), backlights for liquid crystal displays (LCDs) and lasers. This review article first introduces the intrinsic characteristics of 2D semiconductor NPLs with atomic flatness. Subsequently, the approaches and mechanisms for the controlled synthesis of atomically flat NPLs are summarized followed by an insight on recent progress in the mediation of core/shell, core/crown and core/crown@shell structures by selective epitaxial growth of passivation layers on different planes of NPLs. Moreover, an overview of the unique optical properties and the associated light-emitting applications is elaborated. Despite great progress in this research field, there are some issues relating to heavy metal elements such as Cd2+ in NPLs, and the ambiguous gain mechanisms of NPLs and others are the main obstacles that prevent NPLs from widespread applications. Therefore, a perspective is included at the end of this review article, in which the current challenges in this stimulating research field are discussed and possible solutions to tackle these challenges are proposed.

13.
Sci Bull (Beijing) ; 67(5): 529-536, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36546174

RESUMO

Emerging quantum dots (QDs) based light-emitting field-effect transistors (QLEFETs) could generate light emission with high color purity and provide facile route to tune optoelectronic properties at a low fabrication cost. Considerable efforts have been devoted to designing device structure and to understanding the underlying physics, yet the overall performance of QLEFETs remains low due to the charge/exciton loss at the interface and the large band offset of a QD layer with respect to the adjacent carrier transport layers. Here, we report highly efficient QLEFETs with an external quantum efficiency (EQE) of over 20% by employing a dielectric-QDs-dielectric (DQD) sandwich structure. Such DQD structure is used to control the carrier behavior by modulating energy band alignment, thus shifting the exciton recombination zone into the emissive layer. Also, enhanced radiative recombination is achieved by preventing the exciton loss due to presence of surface traps and the luminescence quenching induced by interfacial charge transfer. The DQD sandwiched design presents a new concept to improve the electroluminescence performance of QLEFETs, which can be transferred to other material systems and hence can facilitate exploitation of QDs in a new type of optoelectronic devices.

14.
Front Hum Neurosci ; 16: 985986, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36226262

RESUMO

Aims: Alcohol consumption could lead to a series of health problems and social issues. In the current study, we investigated the resting-state functional brain networks of healthy volunteers before and after drinking through graph-theory analysis, aiming to ascertain the effects of acute alcohol intake on topology and information processing mode of the functional brain networks. Materials and methods: Thirty-three healthy volunteers were enrolled in this experiment. Each volunteer accepted alcohol breathalyzer tests followed by resting-state magnetic resonance imaging at three time points: before drinking, 0.5 h after drinking, and 1 h after drinking. The data obtained were grouped based on scanning time into control group, 0.5-h group and 1-h group, and post-drinking data were regrouped according to breath alcohol concentration (BrAC) into relative low BrAC group (A group; 0.5-h data, n = 17; 1-h data, n = 16) and relative high BrAC group (B group; 0.5-h data, n = 16; 1-h data, n = 17). The graph-theory approach was adopted to construct whole-brain functional networks and identify the differences of network topological properties among all the groups. Results: The network topology of most groups was altered after drinking, with the B group presenting the most alterations. For global network measures, B group exhibited increased global efficiency, Synchronization, and decreased local efficiency, clustering coefficient, normalized clustering coefficient, characteristic path length, normalized characteristic path length, as compared to control group. Regarding nodal network measures, nodal clustering coefficient and nodal local efficiency of some nodes were lower in B group than control group. These changes suggested that the network integration ability and synchrony improved, while the segregation ability diminished. Conclusion: This study revealed the effects of acute alcohol intake on the topology and information processing mode of resting-state functional brain networks, providing new perceptions and insights into the effects of alcohol on the brain.

15.
Angew Chem Int Ed Engl ; 61(40): e202210322, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-35945694

RESUMO

The lagging development of deep-blue perovskite light-emitting diodes (PeLEDs) heavily impedes their practical applications in full-color display due to the absence of spectrally stable emitters and the mismatch of carrier injection capacity. Herein, we report highly efficient deep-blue PeLEDs through a new chemical strategy that addresses the dilemma for simultaneously constant electroluminescence (EL) spectra and high-purify phase in reduced-dimensional perovskites. The success lies in the control of adsorption-energy differences between phenylbutylamine (PBA) and ethylamine (EA) interacting with perovskites, which facilitates narrow n-value distribution. This approach leads to an increased exciton binding energy and enhanced surface potential, hence improving radiative recombination. As a result, an external quantum efficiency of 4.62 % is achieved in PeLEDs with a stable EL peak at 457 nm, demonstrating the best reported result for deep-blue PeLEDs so far.

16.
Adv Mater ; 34(43): e2205217, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35921550

RESUMO

Metal halide perovskites combine excellent electronic and optical properties, such as defect tolerance and high photoluminescence efficiency, with the benefits of low-cost, large-area, solution-based processing. Composition- and dimension-tunable properties of perovskites have already been utilized in bright and efficient light-emitting diodes (LEDs). At the same time, there are still great challenges ahead to achieving operational and spectral stability of these devices. In this review, the origins of instability of perovskite materials, and reasons for their degradation in LEDs are considered. Then, strategies for improving the stability of perovskite materials are reviewed, such as compositional engineering, dimensionality control, defect passivation, suitable encapsulation matrices, and fabrication of core/shell perovskite nanocrystals. For improvement of the operational stability of perovskite LEDs, the use of inorganic charge-transport layers, optimization of charge balance, and proper thermal management are considered. The review is concluded with a detailed account of the current challenges and a perspective on the key approaches and opportunities on how to reach the goal of stable, bright, and efficient perovskite LEDs.

17.
J Fungi (Basel) ; 8(5)2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35628798

RESUMO

Cytochalasans from the endophytic fungi featured structure diversity. Our previous study has disclosed that cytochalasans from the endophytic fungus Phomopsis sp. shj2 exhibited an antimigratory effect. Further chemical investigation on Phomopsis sp. shj2 has led to the discovery of seven new cytochalasans (1-7), together with four known ones. Their structures were elucidated through extensive spectroscopic data interpretation and single-crystal X-ray diffraction analysis. Compounds 1-3 and 8-11 exhibited antimigratory effects against MDA-MB-231 in vitro with IC50 values in the range of 1.01-10.42 µM.

18.
Nano Lett ; 22(10): 4246-4252, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35575706

RESUMO

Significant advancements in perovskite light-emitting diodes (PeLEDs) based on ITO glass substrates have been realized in recent years, yet the overall performance of flexible devices still lags far behind, mainly being ascribed to the high surface roughness and poor optoelectronic properties of flexible electrodes. Here, we report efficient and robust flexible PeLEDs based on a mixed-dimensional (0D-1D-2D-3D) composite electrode consisting of 0D Ag nanoparticles (AgNPs)/1D Ag nanowires (AgNWs)/2D MXene/3D poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). Our designed MXene-based electrodes combine the advantages of facile formation of a film of low-dimensional materials and excellent optical and electrical properties of metal, inorganic, and organic semiconductors, which endow the electrodes with high electrical/thermal conductivity, flexibility, a smooth surface, and good transmittance. Consequently, the resulting flexible PeLEDs (without a light-coupling structure) demonstrate a record external quantum efficiency of 16.5%, a high luminance of close to 50000 cd/m2, a large emitting area of 8 cm2, and significantly enhanced mechanical stability.

19.
Eur J Med Chem ; 236: 114355, 2022 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35413617

RESUMO

The incidence of malignant tumor with high mortality is increasing yearly. CRBN E3 ubiquitin ligase was proved to be an antitumor target. It was found that thalidomide and its analogs could bind to CRBN E3 ubiquitin ligase and modulate CRBN. CRBN modulators could promote the binding of CRBN to specific target proteins or block the binding of CRBN to some endogenous proteins. In this way, CRBN modulators suppress various tumor cells by modulating the interactions between CRBN and various antitumor target proteins. However, almost all CRBN modulators reported include glutarimide scaffold. Therefore, the aim of this study is to developed novel CRBN modulators. Virtual screening methods and bioassay methods, including structural similarity search, molecular docking, substructure search, antitumor evaluation and apoptosis assay were used to search novel potential CRBN modulators in Specs database. Finally, 15 compounds exhibited strong inhibition activity against A549 cells. Among these active compounds, The IC50 value against A549 of AG6033 was 0.853 ± 0.030 µM. Apoptosis assay demonstrated that AG6033 could promote apoptosis of A549 cells. Further mechanism studies suggested that AG6033 caused remarkable decrease of GSPT1 and IKZF1, the substrates of CRBN, and AG6033 induced cytotoxic effects was CRBN-dependent.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Talidomida , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Bioensaio , Simulação de Acoplamento Molecular , Peptídeo Hidrolases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
20.
Small ; 18(19): e2200498, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35419974

RESUMO

The electroluminescence performance and long-term stability of perovskite light-emitting diodes (PeLEDs) are greatly affected by the film quality of perovskite emitting layer. Herein, the authors employ an ionic liquid, 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIm]OTf), to manipulate the growth of quasi-2D perovskite films by providing heterogeneous nucleation sites. The [BMIm]OTf molecules simultaneously realize uniform perovskite films by reducing the contact angles of precursor solution on the hole transport layer (HTL), and eliminate defect states through bonding [BMIm]+ cations to negatively-charged uncoordinated Br and OTf- anions to uncoordinated Pb2+ defects that effectively suppresses the defect states assisted nonradiative recombination in perovskite films. As a result, the efficiency and the operational lifetime of the resultant PeLED are enhanced by more than twofold and threefold, respectively, achieving a maximum external quantum efficiency of 17.6% and an operational lifetime of over 500 min at an initial brightness of 100 cd m-2 .

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