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IL-1R-associated kinases (IRAKs) are signal transducers of the TLR/IL-1R-MyD88-TRAF6 pathways. Vertebrates possess two IRAK lineages, IRAK1/2/3 and IRAK4. In mammals, IRAK4/IRAK1 and IRAK4/IRAK2 are pathway enhancers, whereas IRAK3 is a repressor. However, in bony fish, IRAK2 is absent, and it remains elusive how fish IRAK1/3/4 functionally differ from their mammalian counterparts. In this study, we explored this using the zebrafish model. First, we showed that in human 293T cells, zebrafish IRAK1 and IRAK4 were components of the Myddosome (MyD88-IRAK4-IRAK1) complex, with IRAK1 serving as a potent pathway enhancer. Then, we discovered two zebrafish IRAK3 variants: one (IRAK3a) contains an N-terminal Death domain, a middle pseudokinase domain, and a C-terminal TRAF6-binding domain, whereas the other (IRAK3b) lost both the kinase and TRAF6-binding domains. This truncation of IRAK3 variants could be a conserved phenomenon in fish, because it is also observed in trout and grass carp. We proceeded to show that zebrafish IRAK3a acts as a pathway enhancer by binding with MyD88 and TRAF6, but its activity is milder than IRAK1, possibly because it has no kinase activity. Zebrafish IRAK3b, however, plays a sheer negative role, apparently because of its lack of kinase and TRAF6-binding domains. Moreover, zebrafish IRAK3a/3b inhibit the activity of IRAK1/4, not by interacting with IRAK1/4 but possibly by competing for MyD88 and TRAF6. Finally, we have verified the essential activities of zebrafish IRAK1/3a/3b/4 in zebrafish cells and embryos. In summary, to our knowledge, our findings provide new insights into the molecular functions of fish IRAKs and the evolution of the IRAK functional modes in vertebrates.
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Quinases Associadas a Receptores de Interleucina-1 , Fator 88 de Diferenciação Mieloide , Transdução de Sinais , Fator 6 Associado a Receptor de TNF , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Quinases Associadas a Receptores de Interleucina-1/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Fator 6 Associado a Receptor de TNF/genética , Humanos , Transdução de Sinais/imunologia , Células HEK293 , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genéticaRESUMO
BACKGROUND: The prognosis of fibrolamellar carcinoma (FLC) versus conventional hepatocellular carcinoma (HCC) remains controversial. Thus, this study aimed to compare the prognosis of FLC and HCC. METHODS: Patients with FLC and HCC in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2015 were included. Propensity score matching (PSM) was performed to balance the clinical characteristics between FLC and HCC. Cox regression and Kaplan-Meier analysis were applied to identify the effect of pathology in prognosis before and after match in the whole cohort, as well as in subgroups of fibrosis score, AJCC stage and therapy. RESULTS: A total of 213 patients with FLC and 33365 patients with HCC between 2000 and 2015 were identified. Before matching, the overall survival (OS) and cancer-specific survival (CSS) were significantly better in FLC than HCC. After matching, FLC patients had better OS than HCC patients, but the CSS was similar between groups. Further analyses found that in patients at early stage (AJCC I-III) and/or accepted curative therapy, the prognosis was comparable between HCC and FLC. In patients without cirrhosis (F0), the HCC patients had similar prognosis with FLC patients. Prognosis benefit of FLC was observed in subgroups of AJCC stage IV and non-curative therapy, however, the concomitant diseases may affect the results. CONCLUSIONS: The prognosis of FLC was significantly better than HCC before matching. However, after matching for clinical characteristics, the CSS was comparable between FLC and HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Pontuação de Propensão , Prognóstico , Estudos RetrospectivosRESUMO
The sensitivity of fluorescent lateral flow immunoassay (LFIA) test strips is compromised by the low fluorescence intensity of the signaling molecules. In this study, we synthesized novel phosphorus-doped carbon-dot-based dendritic mesoporous silica nanoparticles (DMSNs-BCDs) with a quantum yield as high as 93.7% to break this bottleneck. Meanwhile, the in situ growth method increased the loading capacity of carbon dots on dendritic mesoporous silica, effectively enhancing the fluorescence intensity of the composite nanospheres. Applied DMSNs-BCDs in LFIA can not only semi-quantitatively detect a single component in a short time frame (procalcitonin (PCT), within 15 min) but also detect the dual components with a low limit of detection (LOD) (carbohydrate antigen 199 (CA199) LOD: 1 U/mL; alpha-fetoprotein (AFP) LOD: 0.01 ng/mL). And the LOD of PCT detection (0.01 ng/mL) is lower by 1.7 orders of magnitude compared to conventional colloidal gold strips. For CA199, the LOD is reduced by a factor of four compared to LFIA using gold nanoparticles as substrates, and for AFP, the LOD is lowered by two orders of magnitude compared to colloidal gold LFIA. Furthermore, the coefficients of variation (CV) for intra-assay and inter-assay measurements are both less than 11%.
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Nanopartículas Metálicas , alfa-Fetoproteínas , Ouro , Corantes , Carbono , Coloide de Ouro , ImunoensaioRESUMO
BACKGROUND/PURPOSE: Both psoriasis and periodontal diseases are characterized by an exaggerated immune response to the microbiota residing on epithelial surfaces. This study aimed to explore the associations between the severity of psoriasis and periodontal destruction in patients with psoriasis. METHODS: Thirty-three patients diagnosed with psoriasis were referred from the dermatology clinic of National Taiwan University Hospital. Full-mouth periodontal examination was performed and saliva was collected after patients signed informed consent forms. The Psoriasis Area Severity Index (PASI) as well as clinical periodontal parameters including probing depth (PD), plaque index (PI), gingival index (GI), and clinical attachment level (CAL) were evaluated. Salivary cytokines including interleukin (IL)-1ß, IL-12, IL-17, interferon-γ, and tumor necrosis factor (TNF)-α were tested with the Luminex Bio-Plex system. Anti-inflammatory medication, tobacco use, and underlying comorbidities were included in the analysis. RESULTS: Baseline PASI was significantly associated with PI. PASI at follow-up was positively correlated with CAL ≥ 4 mm (%) and saliva IL-1ß levels. Psoriasis patients who used non-steroidal anti-inflammatory drugs or topical steroids had significantly lower GI, PD ≥ 4 mm (%), and saliva IL-1ß and TNF-α levels. Moreover, a history of tobacco use was associated with higher PD ≥ 4 mm (%). CONCLUSION: PI, CAL, and salivary IL-1ß were associated with PASI. Periodontal severity was associated with psoriasis involvement. Periodontal inflammation in psoriasis may be modified by anti-inflammatory medication and tobacco use. Additional large-scale longitudinal and mechanistic studies are needed.
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Periodontite , Psoríase , Citocinas , Humanos , Interferon gama , Interleucina-12 , Interleucina-17 , Interleucina-1beta , Periodontite/complicações , Psoríase/complicações , Fator de Necrose Tumoral alfaRESUMO
With the development of open source software (OSS), software reliability has become an important issue. Due to the complexity of OSS development and testing environment, the fault detection rate of OSS will show a variety of changes. The existing OSS reliability models cannot fully adapt to the complex changes of OSS fault detection. In this paper, we proposed a multi-release OSS reliability model based on three-parameter lifetime distribution. The proposed model can effectively adapt to the complicated changes of fault detection in the processes of development and testing of OSS. Experimental results indicate that the proposed model has the better fitting and predictive performance compared with other multi-release OSS reliability models. Moreover, the proposed model can better adapt to the variety of OSS fault detection environment, and assist developers to evaluate the reliability of OSS.
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The global COVID-19 pandemic has severely impacted human health and socioeconomic development, posing an enormous public health challenge. Extensive research has been conducted into the relationship between environmental factors and the transmission of COVID-19. However, numerous factors influence the development of pandemic outbreaks, and the presence of confounding effects on the mechanism of action complicates the assessment of the role of environmental factors in the spread of COVID-19. Direct estimation of the role of environmental factors without removing the confounding effects will be biased. To overcome this critical problem, we developed a Double Machine Learning (DML) causal model to estimate the debiased causal effects of the influencing factors in the COVID-19 outbreaks in Chinese cities. Comparative experiments revealed that the traditional multiple linear regression model overestimated the impact of environmental factors. Environmental factors are not the dominant cause of widespread outbreaks in China in 2022. In addition, by further analyzing the causal effects of environmental factors, it was verified that there is significant heterogeneity in the role of environmental factors. The causal effect of environmental factors on COVID-19 changes with the regional environment. It is therefore recommended that when exploring the mechanisms by which environmental factors influence the spread of epidemics, confounding factors must be handled carefully in order to obtain clean quantitative results. This study offers a more precise representation of the impact of environmental factors on the spread of the COVID-19 pandemic, as well as a framework for more accurately quantifying the factors influencing the outbreak.
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OBJECTIVE: The objective of this review is to conduct a comprehensive and systematic assessment of the efficacy of Yoga as an intervention for knee osteoarthritis (KOA). METHODS: We searched PubMed, Cochrane Library, Embase, Web of Science, and PEDro as of January 3, 2024. Retrieved a total of 200 articles. Standardised mean differences (SMDs) and 95% confidence intervals (CI) were calculated. RESULTS: The study included a total of 8 trials and involved 756 KOA patients. The results indicated that compared to the control group, Yoga exercise showed significant improvements in alleviating pain (SMD = -0.92; 95% CI = -1.64 ~ - 0.20; P = 0.01, I2 = 94%), stiffness (SMD = -0.51; 95% CI = -0.91 ~ -0.12; P = 0.01; I2 = 66%) and physical function (SMD = -0.53; 95% CI = -0.89 ~ -0.17; P = 0.004; I2 = 59%) among KOA patients. However, there was no significant improvement observed in terms of activities of activity of daily living (ADL) (SMD = 1.03; 95% CI = -0.01 ~ 2.07; P = 0.05; I2 = 84%), and quality of life (QOL) (SMD = 0.21; 95% CI = -0.33 ~ 0.74; P = 0.44; I2 = 83%) with the practice of Yoga. CONCLUSIONS: In general, Yoga has been found to be effective in reducing pain and stiffness in KOA patients, it can also improve the physical function of patients. However, there is limited evidence to suggest significant improvements in terms of ADL and QOL.
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Osteoartrite do Joelho , Ensaios Clínicos Controlados Aleatórios como Assunto , Yoga , Humanos , Osteoartrite do Joelho/terapia , Osteoartrite do Joelho/fisiopatologia , Qualidade de Vida , Atividades Cotidianas , Resultado do TratamentoRESUMO
Hepatocellular carcinoma (HCC) treatment is a major challenge. Although andrographolide (Andro) has an anti-proliferation effect on HCC, its underlying mechanism is not yet elucidated, and whether Andro can inhibit HCC metastasis has not been reported. The present study aimed to clarify whether Andro inhibits SK-Hep-1 cell proliferation and HCC metastasis, and the mechanisms. The results showed that Andro significantly reduced the survival of HCC cells and tumor weight and volume in tumor-bearing nude mice. Andro also triggered apoptosis of HCC cells and upregulated MIR22HG, Cleaved Caspase 9/7/3 expression levels, and downregulated BCL-2 mRNA, BCL-2 expression levels. Knockdown of MIR22HG or overexpression of HuR attenuated the effects of Andro on the signal transduction of mitochondrial apoptotic pathway and proliferation ability in HCC cells. Moreover, Andro significantly reduced the invasive ability of the cells and the level of HCC cell lung metastasis, upregulated miR-22-3p expression level and downregulated HMGB1 and MMP-9 expression levels. MIR22HG or miR-22-3p knockdown attenuated the effects of Andro on the signaling of HMGB1/MMP-9 pathway and invasive ability in HCC cells, while the overexpression of HMGB1 attenuated the inhibitory effects of Andro on the MMP-9 expression level and invasive ability in HCC cells. Thus, the regulation of MIR22HG-HuR/BCL-2 and MIR22HG/HMGB1 signaling pathways is involved in the anti-HCC proliferation and metastasis effects of Andro. This study provided a new pharmacological basis for Andro in HCC treatment and, for the first time, identified a natural product molecule capable of positively regulating MIR22HG, which has a robust biological function.
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Carcinoma Hepatocelular , Proteína HMGB1 , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Proteína HMGB1/farmacologia , Proteína HMGB1/uso terapêutico , Metaloproteinase 9 da Matriz/farmacologia , Metaloproteinase 9 da Matriz/uso terapêutico , Camundongos Nus , Linhagem Celular Tumoral , MicroRNAs/genética , Proliferação de Células , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2 , Movimento CelularRESUMO
PURPOSE: Radiation-induced bystander effect (RIBE) frequently is seen as DNA damage in unirradiated bystander cells, but the repair processes initiated in response to that DNA damage are not well understood. RIBE-mediated formation of micronuclei (MN), a biomarker of persistent DNA damage, was previously observed in bystander normal fibroblast (AG01522) cells, but not in bystander human chondrosarcoma (HTB94) cells. The molecular mechanisms causing this disparity are not clear. Herein, we investigate the role of DNA repair in the bystander responses of the two cell lines. METHODS: Cells were irradiated with X-rays and immediately co-cultured with un-irradiated cells using a trans-well insert system in which they share the same medium. The activation of DNA damage response (DDR) proteins was detected by immunofluorescence staining or Western blotting. MN formation was examined by the cytokinesis-block MN assay, which is a robust method to detect persistent DNA damage. RESULTS: Immunofluorescent foci of γH2AX and 53BP1, biomarkers of DNA damage and repair, revealed a greater capacity for DNA repair in HTB94 cells than in AG01522 cells in both irradiated and bystander populations. Autophosphorylation of ATR at the threonine 1989 site was expressed at a greater level in HTB94 cells compared to AG01522 cells at the baseline and in response to hydroxyurea treatment or exposure to 1 Gy of X-rays. An inhibitor of ATR, but not of ATM, promoted MN formation in bystander HTB94 cells. In contrast, no effect of either inhibitor was observed in bystander AG01522 cells, indicating that ATR signaling might be a pivotal pathway to preventing the MN formation in bystander HTB94 cells. Supporting this idea, we found an ATR-dependent increase in the fractions of bystander HTB94 cells with pRPA2 S33 and RAD51 foci. A blocker of RAD51 facilitated MN formation in bystander HTB94 cells. CONCLUSION: Our results indicate that HTB94 cells were likely more efficient in DNA repair than AG01522 cells, specifically via ATR signaling, which inhibited the bystander signal-induced MN formation. This study highlights the significance of DNA repair efficiency in bystander cell responses.
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Proteínas Mutadas de Ataxia Telangiectasia , Efeito Espectador , Condrossarcoma , Reparo do DNA , Rad51 Recombinase , Transdução de Sinais , Humanos , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Efeito Espectador/efeitos da radiação , Linhagem Celular Tumoral , Condrossarcoma/metabolismo , Condrossarcoma/radioterapia , Dano ao DNA , Histonas/metabolismo , Rad51 Recombinase/metabolismoRESUMO
For LiCoO2 (LCO) operated beyond 4.55 V (vs Li/Li+), it usually suffers from severe surface degradation. Constructing a robust cathode/electrolyte interphase (CEI) is effective to alleviate the above issues, however, the correlated mechanisms still remain vague. Herein, a progressively reinforced CEI is realized via constructing ZrâO deposits (ZrO2 and Li2ZrO3) on LCO surface (i.e., Z-LCO). Upon cycle, these ZrâO deposits can promote the decomposition of LiPF6, and progressively convert to the highly dispersed ZrâOâF species. In particular, the chemical reaction between LiF and ZrâOâF species further leads to the densification of CEI, which greatly reinforces its toughness and conductivity. Combining the robust CEI and thin surface rock-salt layer of Z-LCO, several benefits are achieved, including stabilizing the surface lattice oxygen, facilitating the interface Li+ transport kinetics, and enhancing the reversibility of O3/H1-3 phase transition, etc. As a result, the Z-LCO||Li cells exhibit a high capacity retention of 84.2% after 1000 cycles in 3-4.65 V, 80.9% after 1500 cycles in 3-4.6 V, and a high rate capacity of 160 mAh g-1 at 16 C (1 C = 200 mA g-1). This work provides a new insight for developing advanced LCO cathodes.
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BACKGROUND: We aimed to establish a prognostic predictive model based on machine learning (ML) methods to predict the 28-day mortality of acute-on-chronic liver failure (ACLF) patients, and to evaluate treatment effectiveness. METHODS: ACLF patients from six tertiary hospitals were included for analysis. Features for ML models' development were selected by LASSO regression. Models' performance was evaluated by area under the curve (AUC) and accuracy. Shapley additive explanation was used to explain the ML model. RESULTS: Of the 736 included patients, 587 were assigned to a training set and 149 to an external validation set. Features selected included age, hepatic encephalopathy, total bilirubin, PTA, and creatinine. The eXtreme Gradient Boosting (XGB) model outperformed other ML models in the prognostic prediction of ACLF patients, with the highest AUC and accuracy. Delong's test demonstrated that the XGB model outperformed Child-Pugh score, MELD score, CLIF-SOFA, CLIF-C OF, and CLIF-C ACLF. Sequential assessments at baseline, day 3, day 7, and day 14 improved the predictive performance of the XGB-ML model and can help clinicians evaluate the effectiveness of medical treatment. CONCLUSIONS: We established an XGB-ML model to predict the 28-day mortality of ACLF patients as well as to evaluate the treatment effectiveness.
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Background and Aims: The impact of the characteristics of extrahepatic organ failure (EHOF) including the onset time, number, type, and sequence on the prognosis of acute-on-chronic liver failure (ACLF) patients remains unknown. This study aimed to identify the association between the characteristics of EHOF and the prognosis of ACLF patients. Methods: ACLF subjects enrolled at six hospitals in China were included in the analysis. The risk of mortality based on the characteristics of EHOF was evaluated. Survival of study groups was compared by Kaplan-Meier analysis and log-rank tests. Results: A total of 736 patients with ACLF were included. EHOF was observed in 402 patients (54.6%), of which 295 (73.4%) developed single EHOF (SEHOF) and 107 (26.6%) developed multiple EHOF (MEHOF). The most commonly observed EHOF was coagulation failure (47.0%), followed by renal (13.0%), brain (4.9%), respiratory (4.3%), and circulatory (2.3%) failure. Survival analysis found that MEHOF or SEHOF patients with brain failure had a worse prognosis. However, no significant outcome was found in the analysis of the effect of onset time and sequence of failed organs on prognosis. Patients were further divided into three risk subgroups by the EHOF characteristics. Kaplan-Meier analysis showed that risk stratification resulted in the differentiation of patients with different risks of mortality both in the training and validation cohorts. Conclusions: The mortality of ACLF patients was determined by the number and type, but not the onset time and sequence of EHOF. Risk stratification applicable to clinical practice was established.
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Diffuse large B-cell lymphoma (DLBCL) is a commonly diagnosed, aggressive non-Hodgkin's lymphoma. While R-CHOP chemoimmunotherapy is potentially curative, about 40% of DLBCL patients will fail, highlighting the need to identify biomarkers to optimize management. SAMHD1 has a dNTPase-independent role in promoting resection to facilitate DNA double-strand break (DSB) repair by homologous recombination. We evaluated the relationship of SAMHD1 levels with sensitivity to DSB-sensitizing agents in DLBCL cells and the association of SAMHD1 expression with clinical outcomes in 79 DLBCL patients treated with definitive therapy and an independent cohort dataset of 234 DLBCL patients. Low SAMHD1 expression, Vpx-mediated, or siRNA-mediated degradation/depletion in DLBCL cells was associated with greater sensitivity to doxorubicin and PARP inhibitors. On Kaplan-Meier log-rank survival analysis, low SAMHD1 expression was associated with improved overall survival (OS), which on subset analysis remained significant only in patients with advanced stage (III-IV) and moderate to high risk (2-5 International Prognostic Index (IPI)). The association of low SAMHD1 expression with improved OS remained significant on multivariate analysis independent of other adverse factors, including IPI, and was validated in an independent cohort. Our findings suggest that SAMHD1 expression mediates doxorubicin resistance and may be an important prognostic biomarker in advanced, higher-risk DLBCL patients.
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20E (20-Hydroxyecdysone) is a central steroid hormone that orchestrates developmental changes and metamorphosis in arthropods. While its molecular mechanisms have been recognized for some time, detailed elucidation has primarily emerged in the past decade. PCD (Programmed cell death), including apoptosis, necrosis, efferocytosis, pyroptosis, ferroptosis, and autophagy, plays a crucial role in regulated cell elimination, which is vital for cells' development and tissue homeostasis. This review summarizes recent findings on 20E signaling regulated autophagy and apoptosis in insects, including Drosophila melanogaster, Bombyx mori, Helicoverpa armigera, and other species. Firstly, we comprehensively explore the biosynthesis of the sterol hormone 20E and its subsequent signal transduction in various species. Then, we focus on the involvement of 20E in regulating autophagy and apoptosis, elucidating its roles in both developmental contexts and bacterial infection scenarios. Furthermore, our discussion unfolds as a panoramic exposition, where we delve into the fundamental questions with our findings, anchoring them within the grander scheme of our study in insects. Deepening the understanding of 20E-autophagy/apoptosis axis not only underscores the intricate tapestry of endocrine networks, but also offers fresh perspectives on the adaptive mechanisms that have evolved in the face of environmental challenges.
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Sustainable food supply is affected by high energy consumption and negative environmental effects. Regarding the national strategy of "carbon peaking and carbon neutrality targets", the decoupling between energy consumption and economic growth in China's agriculture has received significant attention. Therefore, this study first presents a descriptive analysis of the energy consumption in China's agricultural sector from 2000 to 2019, before analyzing the decoupling state between energy consumption and agricultural economic growth at the national and provincial levels using the Tapio decoupling index. Finally, the logarithmic mean divisia index method is used to decompose the decoupling driving factors. The study draws the following conclusions: (1) At the national level, the decoupling of agricultural energy consumption from economic growth fluctuates among expansive negative decoupling, expansive coupling, and weak decoupling, before stabilizing in the last state. (2) The decoupling process also differs by geographic region. Strong negative decoupling is found in North and East China, and strong decoupling lasts longer in Southwest and Northwest China. (3) The factors driving decoupling are similar at both the levels. The economic activity effect promotes the decoupling of energy consumption. The industrial structure and energy intensity effects are the two main suppressive factors, whereas the population and energy structure effects have relatively weaker impacts. Therefore, based on the empirical results, this study provides evidence for regional governments to formulate policies on the relationship between the agricultural economy and energy management from the perspective of effect driven policies.
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The development of orange-red/red thermally activated delayed fluorescence (TADF) materials with both high emission efficiencies and short lifetimes is highly desirable for electroluminescence (EL) applications, but remains a formidable challenge owing to the strict molecular design principles. Herein, two new orange-red/red TADF emitters, namely AC-PCNCF3 and TAC-PCNCF3, composed of pyridine-3,5-dicarbonitrile-derived electron-acceptor (PCNCF3) and acridine electron-donors (AC/TAC) are developed. These emitters in doped films exhibit excellent photophysical properties, including high photoluminescence quantum yields of up to 0.91, tiny singlet-triplet energy gaps of 0.01 eV, and ultrashort TADF lifetimes of less than 1 µs. The TADF-organic light-emitting diodes employing the AC-PCNCF3 as emitter achieve orange-red and red EL with high external quantum efficiencies of up to 25.0% and nearly 20% at doping concentrations of 5 and 40 wt%, respectively, both accompanied by well-suppressed efficiency roll-offs. This work provides an efficient molecular design strategy for developing high-performance red TADF materials.
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The development of highly efficient orange and red thermally activated delayed fluorescence (TADF) materials for constructing full-color and white organic light-emitting diodes (OLEDs) remains insufficient because of the formidable challenges in molecular design, such as the severe radiationless decay and the intrinsic trade-off between the efficiencies of radiative decay and reverse intersystem crossing (RISC). Herein, we design two high-efficiency orange and orange-red TADF molecules by constructing intermolecular noncovalent interactions. This strategy could not only ensure high emission efficiency via suppression of the nonradiative relaxation and enhancement of the radiative transition but also create intermediate triplet excited states to ensure the RISC process. Both emitters exhibit typical TADF characteristics, with a fast radiative rate and a low nonradiative rate. Photoluminescence quantum yields (PLQYs) of the orange (TPA-PT) and orange-red (DMAC-PT) materials reach up to 94 and 87%, respectively. Benefiting from the excellent photophysical properties and stability, OLEDs based on these TADF emitters realize orange to orange-red electroluminescence with high external quantum efficiencies reaching 26.2%. The current study demonstrates that the introduction of intermolecular noncovalent interactions is a feasible strategy for designing highly efficient orange to red TADF materials.
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Endometriosis is a benign gynecological disease. Accumulating evidence has revealed the participation of dysregulated miRNAs in the progression of endometriosis. Here, the function and molecular mechanism of miR-143-3p in endometriosis were investigated. The levels of vasohibin 1 (VASH1) and miR-143-3p in endometrial tissues and endometriotic stromal cells (ESCs) were detected by RT-qPCR. Migrative and invasive phenotypes of ESCs were tested by Transwell assays. The protein expression of VASH1, TGF-ß signaling markers, and epithelial to mesenchymal transition (EMT) markers was examined by western blotting. The targeted relationship between miR-143-3p and VASH1 was confirmed by bioinformatics analysis and luciferase reporter assay. We found that miR-143-3p expression was significantly upregulated in ectopic endometrial tissues compared to that in eutopic and normal endometrial tissues. MiR-143-3p knockdown restrained EMT process, invasive and migrative behaviors of ESCs. Mechanically, miR-143-3p targeted VASH1 and negatively regulated VASH1. VASH1 downregulation reserved the effects of miR-143-3p knockdown in ESCs. MiR-143-3p activated TGF-ß signaling via targeting VASH1. Furthermore, activation of TGF-ß signaling counteracted the miR-143-3p knockdown-caused suppression of migration, invasion and EMT process in ESCs. Overall, miR-143-3p activates TGF-ß signaling by targeting VASH1 to facilitate migration and invasion of ESCs.
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Endometriose , MicroRNAs , Células Estromais , Proteínas de Ciclo Celular/metabolismo , Movimento Celular/genética , Endometriose/genética , Endometriose/metabolismo , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Células Estromais/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
Cardiomyocyte like cells derived from human pluripotent stem cells (hPSC-CMs) have a good application perspective in many fields such as disease modeling, drug screening and clinical treatment. However, these are severely hampered by the fact that hPSC-CMs are immature compared to adult human cardiomyocytes. Therefore, many approaches such as genetic manipulation, biochemical factors supplement, mechanical stress, electrical stimulation and three-dimensional culture have been developed to promote the maturation of hPSC-CMs. Recently, establishing in vitro synthetic artificial microenvironments based on the in vivo development program of cardiomyocytes has achieved much attention due to their inherent properties such as stiffness, plasticity, nanotopography and chemical functionality. In this review, the achievements and deficiency of reported synthetic microenvironments that mainly discussed comprehensive biological, chemical, and physical factors, as well as three-dimensional culture were mainly discussed, which have significance to improve the microenvironment design and accelerate the maturation of hPSC-CMs.