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The perovskite nanocrystals (PeNCs) are emerging as a promising emitter for light-emitting diodes (LEDs) due to their excellent optical and electrical properties. However, the ultrafast growth of PeNCs often results in large sizes exceeding the Bohr diameter, leading to low exciton binding energy and susceptibility to nonradiative recombination, while small-sized PeNCs exhibit a large specific surface area, contributing to an increased defect density. Herein, Zn2+ ions as a negative catalyst to realize quantum-confined FAPbBr3 PeNCs with high photoluminescence quantum yields (PL QY) over 90%. Zn2+ ions exhibit robust coordination with Br- ions is introduced, effectively retarding the participation of Br- ions in the perovskite crystallization process and thus facilitating PeNCs size control. Notably, Zn2+ ions neither incorporate into the perovskite lattice nor are absorbed on the surface of PeNCs. And the reduced growth rate also promotes sufficient octahedral coordination of PeNC that reduces defect density. The LEDs based on these optimized PeNCs exhibits an external quantum efficiency (EQE) of 21.7%, significantly surpassing that of the pristine PeNCs (15.2%). Furthermore, the device lifetime is also extended by twofold. This research presents a novel approach to achieving high-performance optoelectronic devices.
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Light-emitting diodes (LEDs) based on metal halide perovskites (PeLEDs) with high colour quality and facile solution processing are promising candidates for full-colour and high-definition displays1-4. Despite the great success achieved in green PeLEDs with lead bromide perovskites5, it is still challenging to realize pure-red (620-650 nm) LEDs using iodine-based counterparts, as they are constrained by the low intrinsic bandgap6. Here we report efficient and colour-stable PeLEDs across the entire pure-red region, with a peak external quantum efficiency reaching 28.7% at 638 nm, enabled by incorporating a double-end anchored ligand molecule into pure-iodine perovskites. We demonstrate that a key function of the organic intercalating cation is to stabilize the lead iodine octahedron through coordination with exposed lead ions and enhanced hydrogen bonding with iodine. The molecule synergistically facilitates spectral modulation, promotes charge transfer between perovskite quantum wells and reduces iodine migration under electrical bias. We realize continuously tunable emission wavelengths for iodine-based perovskite films with suppressed energy loss due to the decrease in bond energy of lead iodine in ionic perovskites as the bandgap increases. Importantly, the resultant devices show outstanding spectral stability and a half-lifetime of more than 7,600 min at an initial luminance of 100 cd m-2.
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Light-emitting diodes (LEDs) based on perovskite semiconductor materials with tunable emission wavelength in visible light range as well as narrow linewidth are potential competitors among current light-emitting display technologies, but still suffer from severe instability driven by electric field. Here, we develop a stable, efficient and high-color purity hybrid LED with a tandem structure by combining the perovskite LED and the commercial organic LED technologies to accelerate the practical application of perovskites. Perovskite LED and organic LED with close photoluminescence peak are selected to maximize photon emission without photon reabsorption and to achieve the narrowed emission spectra. By designing an efficient interconnecting layer with p-type interface doping that provides good opto-electric coupling and reduces Joule heating, the resulting green emitting hybrid LED shows a narrow linewidth of around 30 nm, a peak luminance of over 176,000 cd m-2, a maximum external quantum efficiency of over 40%, and an operational half-lifetime of over 42,000 h.
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GSPT1 plays crucial physiological functions, such as terminating protein translation, overexpressed in various tumors. It is a promising anti-tumor target, but is also considered as an "undruggable" protein. Recent studies have found that a class of small molecules can degrade GSPT1 through the "molecular glue" mechanism with strong antitumor activity, which is expected to become a new therapy for hematological malignancies. Currently available GSPT1 degraders are mostly derived from the scaffold of immunomodulatory imide drug (IMiD), thus more active compounds with novel structure remain to be found. In this work, using computer-assisted multi-round virtual screening and bioassay, we identified a non-IMiD acylhydrazone compound, AN5782, which can reduce the protein level of GPST1 and obviously inhibit the proliferation of tumor cells. Some analogs were obtained by a substructure search of AN5782. The structure-activity relationship analysis revealed possible interactions between these compounds and CRBN-GSPT1. Further biological mechanistic studies showed that AN5777 decreased GSPT1 remarkably through the ubiquitin-proteasome system, and its effective cytotoxicity was CRBN- and GSPT1-dependent. Furthermore, AN5777 displayed good antiproliferative activities against U937 and OCI-AML-2 cells, and dose-dependently induced G1 phase arrest and apoptosis. The structure found in this work could be good start for antitumor drug development.
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Antineoplásicos , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos , Bioensayo , Hidrazonas/química , Hidrazonas/farmacología , Hidrazonas/síntesis química , Apoptosis/efectos de los fármacosRESUMEN
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.
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Proteínas Quinasas Activadas por AMP , Amidinas , Medicamentos Herbarios Chinos , Animales , Pez Cebra , Estrés Oxidativo , Fatiga/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Inflamación/tratamiento farmacológico , Antioxidantes , Transducción de Señal , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéuticoRESUMEN
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.
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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.
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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.
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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.
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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.
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Leucemia , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ciclopirox/farmacología , Ciclopirox/metabolismo , Subfamilia K de Receptores Similares a Lectina de Células NK/metabolismo , Células Asesinas Naturales/metabolismo , Transducción de Señal , Leucemia/tratamiento farmacológico , Leucemia/metabolismo , Línea Celular TumoralRESUMEN
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.
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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.
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Neoplasias Pancreáticas , Vía de Señalización Wnt , Animales , Humanos , Ratones , Aciltransferasas/química , Aciltransferasas/genética , Aciltransferasas/metabolismo , beta Catenina/metabolismo , Ligandos , Proteínas de la Membrana/metabolismo , MutaciónRESUMEN
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.
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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.
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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 CâO in the carboxyl groups and Pb dangling bonds.
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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.
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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.
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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.