RESUMO
This study aims to explore the pharmacological substance basis of Qi Ge Decoction (QG) in antihyperlipidemia through a combination of metabolomics and serum pharmacochemistry. We used ultra-performance liquid chromatography quadrupole-time-of-flight/MS (UPLC Q-TOF/MS) to analyze and identify the chemical constituents of QG in vitro and in blood chemical components. The metabolomics technology was used to analyze serum biomarkers of QG in preventing and treating hyperlipidemia. We constructed a mathematical model of the relationship between constituents absorbed into the blood and endogenous biomarkers and explored the potential therapeutic application of QG for the prevention and treatment of hyperlipidemia. Compared with the model group, the levels of total cholesterol and triglyceride in the QG group were significantly decreased (P < 0.01). A total of 12 chemical components absorbed into the blood were identified, and 48 biomarkers of the hyperlipidemia model were obtained from serum metabolomic analysis, of which 15 metabolites were backregulated after QG intervention. Puerarin, hesperetin, puerarin xyloside, calycosin, and monohydroxy-tetramethoxyflavone had a high correlation with the biomarkers regulated by QG. This study elucidated the material basis of QG in the intervention of hyperlipidemia, thereby facilitating future research aimed at further revealing the pharmacodynamic material basis of QG's antihyperlipidemic effects.
Assuntos
Medicamentos de Ervas Chinesas , Hiperlipidemias , Hipolipemiantes , Metabolômica , Metabolômica/métodos , Hipolipemiantes/sangue , Hipolipemiantes/farmacocinética , Hipolipemiantes/química , Cromatografia Líquida de Alta Pressão/métodos , Animais , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/sangue , Masculino , Biomarcadores/sangue , Ratos , Metaboloma/efeitos dos fármacos , Ratos Sprague-Dawley , Espectrometria de Massas/métodosRESUMO
The aim of this work was to explore the differences between various pharmaceutical processes in combined solutions of a single decoction (QGHBY) and a combined decoction (QGHJY) of Qi-Ge decoction from the perspective of chemical composition changes, so as to further guide the clinical application of drugs. A combined solution of a single decoction and a combined decoction of Astragali Radix, Puerariae Lobatae Radix and Citri Reticulatae Chachiensis Pericarpium was prepared with the same technological parameters. The chemical components of the two were detected and identified based on UPLC-Q-TOF/MS, and the different components were determined by principal component analysis. Eighty-eight compounds were identified in the pharmaceutical solution of Qi-Ge decoction. Principal component analysis revealed 11 different components of QGHBY and QGHJY with the conditions of Variable Importance in Projection (VIP) ≥ 1, fold change ≥ 2 and p < 0.05, among which hesperidin, hesperitin, isosinensetin, sinensetin and 5-demethylnobiletin were the components of Citri Reticulatae Chachiensis Pericarpium. The levels of these 11 different components in QGHJY were higher than those of QGHBY. The combined decoction is beneficial for the dissolution of flavonoids and other chemical components, and there is a significant difference in the content of chemical components between modern herbal concentrate granules and traditional decoctions.
Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Análise de Componente Principal , Flavonoides/análise , Flavonoides/químicaRESUMO
In this study, we focused on studying the changes in urine metabolites in hyperlipidemic rats using ultra-performance liquid chromatography coupled with quadrupole time-of-fight mass spectrometry (UPLC-Q-TOF/MS) and metabolomics, as well as the effect of Citri Reticulatae Chachiensis Pericarpium (CRCP) on hyperlipidemia. These urine samples were examined by UPLC-Q-TOF/MS to obtain MS data. The MS data were analyzed by principal component analysis and partial least squares-discriminant analysis to identify the differential metabolites. CRCP reduced the body weight and levels of triglycerides, total cholesterol and low-density lipoprotein cholesterol and abnormally decreased high-density lipoprotein cholesterol in hyperlipidemic rats, which were significantly raised by a high-fat diet. Twenty-seven potential biomarkers were identified within the complex sample matrix of urine. Fourteen biomarkers increased in the hyperlipidemia rats compared with normal rats. Meanwhile, 13 biomarkers decreased. CRCP reversed abnormal changes in biomarkers, including 5-l-glutamyl-taurine, 5-aminopentanoic acid, cis-4-octenedioic acid and 2-octenedioic acid. These biomarkers show that hyperlipidemia is related to the metabolic pathways of taurine and hypotaurine metabolism, fatty acid biosynthesis, and arginine and proline metabolism. CRCP mainly prevents hyperlipidemia by intervening in these metabolic pathways.
Assuntos
Citrus/química , Dieta Hiperlipídica , Metaboloma/efeitos dos fármacos , Preparações de Plantas , Substâncias Protetoras , Animais , Biomarcadores/urina , Frutas/química , Masculino , Metabolômica , Preparações de Plantas/química , Preparações de Plantas/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos TestesRESUMO
Although freeze-drying is an excellent method for preserving microorganisms, it inevitably reduces cell activity and function. Moreover, probiotic strains differ in terms of their sensitivity to the freeze-drying process. Therefore, it is necessary to optimize the variables relevant to this process. The pre-freezing temperature is a critical parameter of the freeze-drying process, but it remains unclear whether the optimal pre-freezing temperature differs among strains and protectants. This study explored the effects of 4 different pre-freezing temperatures on the survival rates of different Lactobacillus plantarum strains after freeze-drying in the presence of different protectants. Using phosphate-buffered saline solution and sorbitol as protectants, pre-freezing at -196°C, -40°C, and -20°C ensured the highest survival rates after freeze-drying for AR113, AR307, and WCFS1, respectively. Using trehalose, pre-freezing at -20°C ensured the best survival rate for AR113, and -60°C was the best pre-freezing temperature for AR307 and WCFS1. These results indicate that the pre-freezing temperature can be changed to improve the survival rate of L. plantarum, and that this effect is strain-specific. Further studies have demonstrated that pre-freezing temperature affected viability via changes in cell membrane integrity, membrane permeability, and lactate dehydrogenase activity. In summary, pre-freezing temperature is a crucial factor in L. plantarum survival after freeze-drying, and the choice of pre-freezing temperature depends on the strain and the protectant.
Assuntos
Crioprotetores/farmacologia , Lactobacillus plantarum/fisiologia , Probióticos , Trealose/farmacologia , Animais , Temperatura Baixa , Liofilização/veterinária , CongelamentoRESUMO
Breaking the intrinsic rule of semiconductors that conductivity increases with increase of temperature and realizing a dramatic dropping of conductivity at high temperature may arouse new intriguing applications, such as circuit overload or over-temperature protecting. This goal has now been achieved through T-type electron-transfer photochromism of one organic semiconductor assembled by intermolecular cationâ â â π interactions. Conductivity of the viologen-based model semiconductor (H2 bipy)(Hox)2 (H2 bipy=4,4'-bipyridin-1,1'-dium; ox=oxalate) increased by 2 orders of magnitude after photoinduced electron transfer (a record for photoswitchable organic semiconductors) and generation of radical cationâ â â π interactions, and fell by approximately 81 % at 100 °C through reverse electron transfer and degeneration of the radical cationâ â â π interactions. The model semiconductor has at least two different electron transfer pathways in the decoloration process.
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Formaldehyde (FA), a ubiquitous environmental pollutant, has long been suspected of causing adverse male reproductive effects. However, the molecular and cellular mechanisms underlying this phenomenon remain elusive. The overall aim of this study is to clarify the role of mammalian target of rapamycin (mTOR) in male reproductive injuries induced by FA exposure, by which we can further understand the molecular mechanism of FA male reproductive toxicity. In this study, immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction analysis were used to detect the expression of mTOR molecule in testicular tissues. We found that FA exposure inhibits the expression of mTOR in a dose-dependent manner. Combined with our earlier finding, we found the decreasing expression of mTOR in testicular tissue were consistent with the changes of testicular structure and autophagy levels. In summary, our data suggested that mTOR molecule might be involved in male reproductive injuries induced by FA exposure.
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A novel minor bisindole alkaloid, racemosin C (1), characterized by a naturally unprecedented 8-hydroxy-2,4,6-cyclooctatrienone ring fused with two indole systems, was isolated from the green alga Caulerpa racemosa, together with one known related metabolite, caulersin (2). The structure of 1 was elucidated on the basis of extensive spectroscopic analysis, and by comparison with the data of related known compounds. A plausible biosynthetic pathway of 1 was proposed. Compounds 1 and 2 exhibited significant PTP1B inhibitory activity with IC50 values of 5.86 ± 0.57 and 7.14 ± 1.00 µM, respectively, compared with the positive control oleanolic acid (IC50 = 3.03 ± 0.20 µM). On the basis of the data obtained, the Caulerpa bisindole alkaloids may be considered as a new class of PTP1B inhibitors.
Assuntos
Caulerpa/química , Alcaloides Indólicos/isolamento & purificação , Alcaloides Indólicos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Alcaloides Indólicos/química , Isoquinolinas , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oceanos e Mares , Ácido Oleanólico/químicaRESUMO
Pulmonary arterial hypertension (PAH) is a perilous disease that precipitates right ventricular hypertrophy, induces right heart failure, and exerts deleterious ramifications on prognostic outcomes. The establishment of atrial communication can create a right-to-left shunt, thereby ameliorating hemodynamic parameters. Previous reports suggested that opening of a patent foramen ovale (PFO) was common in patients with severe PAH, but exhibited no discernible impact on long-term survival. We reported the case of a 39-year-old man with severe idiopathic PAH, who underwent reopening of the PFO due to severe cough and hemoptysis, followed by a marked amelioration in symptoms and a substantial decrease in pulmonary arterial pressure. The patient has survived for more than 12 years, persisting in World Health Organization functional class â ¡ with mild PAH.
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Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells (ECs) that play an important role in liver development and regeneration. Additionally, it is involved in various pathological processes, including steatosis, inflammation, fibrosis and hepatocellular carcinoma. However, the rapid dedifferentiation of LSECs after culture greatly limits their use in vitro modeling for biomedical applications. In this study, we developed a highly efficient protocol to induce LSEC-like cells from human induced pluripotent stem cells (hiPSCs) in only 8 days. Using single-cell transcriptomic analysis, we identified several novel LSEC-specific markers, such as EPAS1, LIFR, and NID1, as well as several previously revealed markers, such as CLEC4M, CLEC1B, CRHBP and FCN3. These LSEC markers are specifically expressed in our LSEC-like cells. Furthermore, hiPSC-derived cells expressed LSEC-specific proteins and exhibited LSEC-related functions, such as the uptake of acetylated low density lipoprotein (ac-LDL) and immune complex endocytosis. Overall, this study confirmed that our novel protocol allowed hiPSCs to rapidly acquire an LSEC-like phenotype and function in vitro. The ability to generate LSECs efficiently and rapidly may help to more precisely mimic liver development and disease progression in a liver-specific multicellular microenvironment, offering new insights into the development of novel therapeutic strategies.
Assuntos
Diferenciação Celular , Células Endoteliais , Células-Tronco Pluripotentes Induzidas , Fígado , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/citologia , Fígado/metabolismo , Fígado/citologia , Análise de Célula Única/métodos , Células Cultivadas , Biomarcadores/metabolismo , Lipoproteínas LDL/metabolismo , Perfilação da Expressão GênicaRESUMO
Monodispersed microspheres play a major role in optical science and engineering, providing ideal building blocks for structural color materials. However, the method toward high solid content (HSC) monodispersed microspheres has remained a key hurdle. Herein, a facile access to harvest monodispersed microspheres based on the emulsion polymerization mechanism is demonstrated, where anionic and nonionic surfactants are employed to achieve the electrostatic and steric dual-stabilization balance in a synergistic manner. Monodispersed poly(styrene-butyl acrylate-methacrylic acid) colloidal latex with 55 wt% HSC is achieved, which shows an enhanced self-assembly efficiency of 280% compared with the low solid content (10 wt%) latex. In addition, Ag-coated colloidal photonic crystal (Ag@CPC) coating with near-zero refractive index is achieved, presenting the characteristics of metamaterials. And an 11-fold photoluminescence emission enhancement of CdSe@ZnS quantum dots is realized by the Ag@CPC metamaterial coating. Taking advantage of high assembly efficiency, easily large-scale film-forming of the 55 wt% HSC microspheres latex, robust Ag@CPC metamaterial coatings could be easily produced for passive cooling. The coating demonstrates excellent thermal insulation performance with theoretical cooling power of 30.4 W m-2, providing practical significance for scalable CPC architecture coatings in passive cooling.
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Two new prenylated para-xylenes, named caulerprenylols A (1) and B (2), were isolated from the green alga Caulerpa racemosa, collected from the Zhanjiang coastline, China. The structures of the two metabolites were elucidated on the basis of detailed spectroscopic analysis. This is the first report of prenylated para-xylenes from marine algae and from marine organisms as well. Moreover, caulerprenylol B (2) is also characterized by an uncommon indane ring system. In in vitro bioassays, the new compounds exhibited a broad spectrum of antifungal activity against Candida glabrata (537), Trichophyton rubrum (Cmccftla), and Cryptococcus neoformans (32609) with MIC80 values between 4 and 64 µg/mL when compared to amphotericin B (MIC80 values of 2.0, 1.0, and 4.0 µg/mL, respectively) as a positive control and showed no growth inhibition activity against the tumor cells HL60 and A549.
Assuntos
Antifúngicos/química , Caulerpa/química , Xilenos/química , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Candida glabrata/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Células HL-60 , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Trichophyton/efeitos dos fármacos , Xilenos/isolamento & purificação , Xilenos/farmacologiaRESUMO
By the coordination assembly of a redox photoactive functional motif and a cyanide-bridged moiety, a cyanide-bridged MnII-FeIII compound with large photoinduced magnetic change at room-temperature due to photoinduced electron transfer was obtanied. This compound also shows unprecedented radical-quenched spin glass in molecule based magnets.
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With the development of the social economy, unhealthy living habits and eating styles are gradually affecting people's health in recent years. As a chronic liver disease, NAFLD is deeply affected by unhealthy living habits and eating styles and has gradually become an increasingly serious public health problem. As a protein complex in clinical research, the inflammasomes play a crucial role in the development of NAFLD, atherosclerosis, and other diseases. This paper reviews the types, composition, characteristics of inflammasomes, and molecular mechanism of the inflammasome in NAFLD. Meanwhile, the paper reviews the drugs and non-drugs that target NLRP3 inflammasome in the treatment of NAFLD in the past decades. we also analyzed and summarized the related experimental models, mechanisms, and results of NAFLD. Although current therapeutic strategies for NAFLD are not effective, we expect that we will be able to find an appropriate treatment to address this problem in the future with further research on inflammasome.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fígado/metabolismoRESUMO
A new design strategy through the synergy of Mo(vi)-Mo(v) intervalence charge transfer and π(radical)-π(radical/cation) interactions is proposed to obtain semiconductors with photoresponsive ranges covering the whole UV-SWIR (ultraviolet-shortwave near-infrared; ca. 250-3000 nm) region. With this strategy, a viologen-based molybdate semiconductor with a UV-SWIR photoresponsive range was obtained through UV/X-ray irradiation or thermal annealing. The thermally annealed semiconductor has the highest conversion and the best photocurrent response in the range of 355-2400 nm.
RESUMO
Colloidal photonic crystals (CPCs) with a highly ordered crystal structure have attracted great attention in displays, colorimetric sensors and solar energy utilization fields. However, the easily cracking microstructure, inferior assembly efficiency and low refractive index contrast result in poor structural colors. Herein, we develop core-shell poly(styrene-acrylic)@polypyrrole (P(St-AA)@PPy) colloidal nanoparticles by the in situ chemical coupling reaction via droplet microfluidic technology. By membrane separation-assisted assembly (MSAA) and electrostatic spraying strategies, the P(St-AA)@PPy colloidal nanoparticles are assembled into the CPC film, which presents high assembly efficiency and saturated angle-independent structural colors, due to the light-absorbing PPy shell and hydrogen-bond interaction between nanoparticles. Benefitting from these outstanding performances, the P(St-AA)@PPy film shows excellent photothermal properties, which can realize a solar vaporization rate of 1.5825 kg m-2 h-1, corresponding to a light-to-vapor efficiency of 94.20%, under 1.0 sun solar irradiance conditions. Our findings open a path for the design of functional CPCs and new-generation photothermal applications.
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Potato virus X (PVX) is one of the most common plant viruses that cause great economic losses to solanaceous plants. We have previously reported the complete genomic sequence of the 2006 Chinese potato isolate FX21 and demonstrated that PVX isolates cluster into two groups: Eurasia and America. Here, we present the complete genomic sequence of one PVX isolate collected from potato in 1985 (PVX-1985). The genome of PVX-1985 is identical to that of FX21 in length and has the same genomic structure. PVX-1985, which like FX21 fell within the Eurasia group, clustered together with isolates from Europe, whereas FX21 clustered together with isolates of primarily Asian origin. Phylogenetic analyses of the complete genomic sequences and of CP gene sequences showed that Chinese PVX isolates have different origins and were introduced via multiple events. Though all the open reading frames of PVX are under negative/purifying selection, the central region of RNA-dependent RNA polymerase is under positive/diversifying selection.
Assuntos
Genoma Viral , Filogenia , Doenças das Plantas/virologia , Potexvirus/genética , Potexvirus/isolamento & purificação , RNA Viral/genética , Solanum tuberosum/virologia , China , Análise por Conglomerados , Epidemiologia Molecular , Dados de Sequência Molecular , Polimorfismo Genético , Potexvirus/classificação , Análise de Sequência de DNARESUMO
This study aimed to analyze changes in nuclear factor-kappa B (NF-kappaB), inflammation factors, and macrophages in pulmonary tissue under deep hypothermia circulatory arrest (DHCA) at different time points, which can be used to infer the role of early macrophage activation and NF-kappaB activity in pulmonary injury. The possible pathogenic mechanisms of DHCA-induced pulmonary injury were investigated in this study to provide an experimental basis for clinical lung protective strategies. Piglets (n = 12) were randomly divided into 2 groups, with 6 piglets in each group. The control group had ambient temperature cardiopulmonary bypass (CPB), and the experimental group had DHCA. Both groups had conventional CPB with 30 min of parallel circulation. Changes in NF-kappaB and inflammatory factors were examined in each group at 6 different time points. At 0.5 h after ischemia-reperfusion, NF-kappaB expression in the nucleus of pulmonary tissue reached its peak, and brown-stained nuclei were mainly polymorphonuclear antibodies. At 1 h after ischemia-reperfusion, plasma tumor-necrosis factor (TNF)-alpha in the experimental group was significantly increased compared with that before reperfusion (P < 0.05). The plasma levels of interleukin (IL)-8 and IL-6 in the experimental group were significantly increased at 1.5 h after ischemia-reperfusion compared with the levels before reperfusion (P < 0.05). Early activation of NF-kappaB under DHCA might play an important role in DHCA-induced pulmonary injury.
Assuntos
Parada Circulatória Induzida por Hipotermia Profunda/efeitos adversos , Lesão Pulmonar/fisiopatologia , Ativação de Macrófagos , NF-kappa B/sangue , Traumatismo por Reperfusão/fisiopatologia , Animais , Humanos , Imuno-Histoquímica , Interleucina-6/sangue , Interleucina-8/sangue , Lesão Pulmonar/etiologia , Distribuição Aleatória , Traumatismo por Reperfusão/etiologia , Suínos , Fator de Necrose Tumoral alfa/sangueRESUMO
Extending photoresponse ranges of semiconductors to the entire ultraviolet-visible (UV)-shortwave near-infrared (SWIR) region (ca. 200-3000 nm) is highly desirable to reduce complexity and cost of photodetectors or to promote power conversion efficiency of solar cells. The observed up limit of photoresponse for organic-based semiconductors is about 1800 nm, far from covering the UV-SWIR region. Here we develop a cyanide-bridged layer-directed intercalation approach and obtain a series of two viologen-based 2D semiconductors with multispectral photoresponse. In these compounds, infinitely π-stacked redox-active N-methyl bipyridinium cations with near-planar structures are sandwiched by cyanide-bridged MnII-FeIII or ZnII-FeIII layers. Radical-π interactions among the infinitely π-stacked N-methyl bipyridinium components favor the extension of absorption range. Both semiconductors show light/thermo-induced color change with the formation of stable radicals. They have intrinsic photocurrent response in the range of at least 355-2400 nm, which exceeds all reported values for known single-component organic-based semiconductors.
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Metal-organic framework (MOF)-directed photonic structure materials have inspired great attention for extended and enhanced functions. However, the direct construction of photonic crystals (PCs) with MOF particles as building blocks still remains a challenge. Herein, we designed and synthesized monodisperse polyamidoamine (PAMAM) dendrimer-modified zeolitic imidazolate framework (ZIF-8) particles (PAMAM@ZIF-8) via a postsynthetic method, rendering ZIF-8 with hydrophilicity. It was found that the PAMAM@ZIF-8 particles could directly assemble into a uniform photonic structure and effectively suppressed the coffee-ring effect, forming homogeneous PC films with different structural colors. A PC pattern with angle-dependent colors was also achieved, which might have potential applications in the field of anticounterfeiting printing. More importantly, by taking advantages of a membrane separation-assisted assembly process, a colorful and robust PC film was accomplished on the surface of reduced graphene oxide (rGO). The hierarchal PAMAM@ZIF-8/rGO film demonstrates a superior separation ability toward organic dye solutions, which enriches the function of PC materials. This work gives a new insight into the fabrication of MOF-based functional PC materials, which will extend the application of PCs in the high selective and effective separation field.
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Hydrophobic photonic crystals (PCs) has been increasingly appreciated as a promising functional material due to their distinct surface characteristic of structural color and hydrophobicity. However, it remains a challenge to fabricate hydrophobic PCs via a one-step process. Inspired by the development of high-performance waterborne coatings, we propose an easy-to-perform and high-efficiency strategy to construct hydrophobic building blocks (diameter of 221, 247, 276 and 305 nm), where the umbelli-form hydrophobic long chain (veova10 Cn > 9) was loaded onto polystyrene (PS) colloidal particles in situ. Taking advantage of the hydrophobic driving force between the colloidal particles, large-scale colloidal photonic crystals (CPCs) film with crack-free morphology was obtained efficiently. The derived CPCs exhibit robust mechanical stability, prominent hydrophobicity and excellent optical properties. In addition, the colloidal latex holds great potential toward PCs coatings on a variety of substrates (glass, plastic and steel) with excellent adhesiveness. Furthermore, we contrive to construct angle-independent structural color films and supraballs, and explore their application in quantum dots (QDs) fluorescence enhancement, which achieved an enhancement effect by more than eight times. From the standpoint of practical applications, we achieved the flexible high-brightness wearable light-emitting diode (LED) displays. This work will lay a foundation for the development of high-efficiency PCs building blocks, and indicate the direction for the meaningful application of CPCs.