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Multi-resonance thermally activated delayed fluorescence (MR-TADF) materials hold great promise for advanced high-resolution organic light-emitting diode (OLED) displays. However, persistent challenges, such as severe aggregation-caused quenching (ACQ) and slow spin-flip, hinder their optimal performance. We propose a synergetic steric-hindrance and excited-state modulation strategy for MR-TADF emitters, which is demonstrated by two blue MR-TADF emitters, IDAD-BNCz and TIDAD-BNCz, bearing sterically demanding 8,8-diphenyl-8H-indolo[3,2,1-de]acridine (IDAD) and 3,6-di-tert-butyl-8,8-diphenyl-8H-indolo[3,2,1-de]acridine (TIDAD), respectively. These rigid and bulky IDAD/TIDAD moieties, with appropriate electron-donating capabilities, not only effectively mitigate ACQ, ensuring efficient luminescence across a broad range of dopant concentrations, but also induce high-lying charge-transfer excited states that facilitate triplet-to-singlet spin-flip without causing undesired emission redshift or spectral broadening. Consequently, implementation of a high doping level of IDAD-BNCz resulted in highly efficient narrowband electroluminescence, featuring a remarkable full-width at half-maximum of 34â nm and record-setting external quantum efficiencies of 34.3 % and 31.8 % at maximum and 100â cd m-2, respectively. The combined steric and electronic effects arising from the steric-hindered donor introduction offer a compelling molecular design strategy to overcome critical challenges in MR-TADF emitters.
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Malnutrition has been reported to be associated with reduced survival and deficient anticancer immunity, and undernourishment is a frequent comorbidity in head and neck cancer (HNC) patients. In this study, we evaluated the relationship between nutritional status and immunologic factors, and its prognostic value for HNC. We retrospectively reviewed 212 HNC patients who had undergone a nutrition evaluation based on the Patient-Generated Subjective Global Assessment (PG-SGA) and curative radiotherapy (RT). The role of nutritional status in the prognosis of HNC and its correlation with anticancer immune response was assessed in HNC patients, and in the 4-nitroquinoline 1-oxide (4NQO)-induced tongue tumor animal model. Our data revealed that malnutrition (high PG-SGA scores) was significantly associated with more advanced disease, lower body mass index, lower RT completion rates, and reduced survival. Patients in the group with high PG-SGA scores had a higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived suppressor cells (MDSCs), and elevated IL-6 levels in the peripheral circulation. Patients with increased PG-SGA scores following treatment were more likely to developing locoregional failure. In the 4NQO-induced tumor model, nutritional supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. Following ectopic tumor implantation in an immunocompetent host, nutrition supplements decreased tumor growth in association with attenuated MDSC recruitment and lower IL-6 expression. In conclusion, malnutrition by PG-SGA was associated with poor prognosis in HNC patients. Based on the data of HNC patients and the 4NQO-tumor model, adequate nutritional supplementation might improve the prognosis associated with augmented anticancer immunity.
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Neoplasias de Cabeza y Cuello , Desnutrición , Humanos , Estado Nutricional , Pronóstico , Estudios Retrospectivos , Interleucina-6 , Desnutrición/complicaciones , Microambiente TumoralRESUMEN
Rationally tuning the emission position and narrowing the full width at half-maximum (FWHM) of an emitter is of great importance for many applications. By synergistically improving rigidity, strengthening the resonant strength, inhibiting molecular bending and rocking, and destabilizing the HOMO energy level, a deep-blue emitter (CZ2CO) with a peak wavelength of 440â nm and an ultranarrow spectral FWHM of 16â nm (0.10â eV) was developed via intramolecular cyclization in a carbonyl/N resonant core (QAO). The dominant υ0-0 transition character of CZ2CO gives a Commission Internationale de I'Éclairage coordinates (CIE) of (0.144, 0.042), nicely complying with the BT.2020 standard. Moreover, a hyper-fluorescent device based on CZ2CO shows a high maximum external quantum efficiency (EQEmax ) of 25.6 % and maintains an EQE of 22.4 % at a practical brightness of 1000â cd m-2 .
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The development of photoinduced luminescent radicals with dynamic emission color is still challenging. Herein we report a novel molecular radical system (TBIQ) that shows photo-controllable luminescence, leading to a wide range of ratiometric color changes via light excitation. The conjugated skeleton of TBIQ is decorated with steric-demanding tertiary butyl groups that enable appropriate intermolecular interaction to make dynamic intermolecular coupling possible for controllable behaviors. We reveal that the helicenic pseudo-planar conformation of TBIQ experiences a planarization process after light excitation, leading to more compactly stacked supermolecules and thus generating radicals via intermolecular charge transfer. The photo-controllable luminescent radical system is employed for a high-level information encryption application. This study may offer unique insight into molecular dynamic motion for optical manufacturing and broaden the scope of smart-responsive materials for advanced applications.
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Thermally activated delayed fluorescence (TADF) materials with extremely small singlet-triplet energy offsets have opened new horizons for the development of metal-free photosensitizers for photodynamic therapy (PDT) in recent years. However, the exploration of near-infrared (NIR) TADF emitters for efficient two-photon-excited (TPE) PDT is still a formidable challenge, thus it has not been reported yet. In this study, purely organic photosensitizers (PSs) based on the TADF nanoparticles (NIR-TADF NPs) are designed for efficient TPE-PDT, which show excellent singlet oxygen generation ability. Thanks to the intrinsic two-photon excitation and NIR emission characteristics, the NIR-TADF NPs demonstrate promising potential in both single-photon-excited (SPE) and TPE NIR imaging. More importantly, the anti-tumor efficiency and biosafety of TADF-based PSs at the small animal level are confirmed in A549 tumor xenograft models under TPE laser irradiance, which will facilitate the practical biomedical applications of TADF materials. This work not only provides a promising strategy to develop metal-free PSs, but also expands the applied scope of TADF-based nanotherapeutics and advances their possible clinical translation in cancer therapy.
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Nanopartículas , Fotoquimioterapia , Animales , Fluorescencia , Humanos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Oxígeno SingleteRESUMEN
Adequately harvesting all excitons in a single molecule and inhibiting exciton losses caused by intermolecular interactions are two important factors for achieving high efficiencies thermally activated delayed fluorescence (TADF). One potential approach for optimizing these is to tune alignment of various excited state energy levels by using different doping concentrations. Unfortunately, emission efficiencies of most TADF emitters decrease rapidly with concentrations which limits the window for energy level tunning. In this work, by introducing a spiro group to increase steric hindrance of a TADF emitter (BPPXZ) with a phenoxazine and a dibenzo[a,c]phenazine, emission efficiency of the resulting molecule (BPSPXZ) is much less affected by concentration increase. This enables exploitation of the concentration effects to tune energy levels of its excited states for obtaining simultaneously small singlet-triplet energy offset and large spin-orbital coupling, leading to high-efficiency reverse intersystem crossing. With these merits, organic light-emitting diodes (OLEDs) using the BPSPXZ emitter from 5 to 60 wt% doping can all deliver EQE of over 20%. More importantly, record-high EQEs of 33.4% and 15.8% are respectively achieved in the optimized and nondoped conditions. This work proposes a strategy for developing red TADF emitters by optimizing the intermolecular interaction and energy level alignments to facilitate exciton utilization over wide doping concentrations.
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BACKGROUND: We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps. METHODS: From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (n = 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable. RESULTS: Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age < 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm, margin > 4 mm, extranodal extension (ENE), and adjuvant therapy (all p < 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival [OS]), age ≥ 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio [HR] 1.26, 82%/77%; p = 0.0100) and OS (HR 1.21, 73%/68%; p = 0.0079). CONCLUSIONS: After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.
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Colgajos Tisulares Libres , Neoplasias de Cabeza y Cuello , Anciano , Humanos , Masculino , Estadificación de Neoplasias , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
BACKGROUND: This study aimed to investigate the prognostic factors and the utility of the neoadjuvant rectal (NAR) score for patients who have locally advanced rectal cancer (LARC) treated with preoperative short-course radiotherapy (SRT) or long-course concurrent chemoradiotherapy (CRT). METHODS: Of 314 consecutive stage 2 or 3 rectal cancer patients enrolled from January 2006 to December 2017, 205 underwent preoperative SRT (2500 cGy/5 fractions), and 109 underwent preoperative CRT (4200-5080 cGy/21-28 fractions) after total mesorectal excision (TME). The study calculated NAR scores using the following equation: [5 pN - 3(cT - pT) + 12]2/9.61. RESULTS: The multivariate analysis showed that age above 65 years, pT4, pN2, NAR scores higher than 16, and distance from anal verges (< 8 cm) were significant prognostic factors for overall survival (OS), whereas, pN2, NAR scores lower than 16, and distance from anal verges (< 8 cm) were significant prognostic factors for disease-free survival (DFS) and distant metastasis (DM). The patients with an NAR score higher than 16, had a 5-year OS rate of 67.6%, a DFS rate of 56.9%, a locoregional recurrence (LRR) rate of 7.7%, and a DM rate of 35% compared with corresponding rates of 87.6%, 76.7%, 5.4%, and 7.2% for the patients with an NAR score of 16 or lower (p < 0.001 for OS, < 0.001 for DFS, 0.25 for LRR, and < 0.001 for DM). CONCLUSIONS: For patients who undergo SRT or CRT for LARC, a higher NAR score is associated with worse OS and DFS and higher DM rates at 5 years. The NAR score could be used as a short-term surrogate end point after neoadjuvant therapy for LARC.
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Neoplasias del Recto , Anciano , Quimioradioterapia , Supervivencia sin Enfermedad , Humanos , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Pronóstico , Neoplasias del Recto/patología , Neoplasias del Recto/terapiaRESUMEN
BACKGROUND: This study evaluated the treatment outcomes of the primary surgery (PS) or concurrent chemoradiotherapy (CCRT) as the initial treatment for hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: This retrospective cohort study included patients with stages III-IV HPSCC from four tertiary referral centers consecutively enrolled from 2003 to 2012; of them, 213 (32.6%) and 439 (67.4%) had received PS and CCRT as their primary treatments, respectively. The 5-year overall survival (OS) and disease-free survival (DFS) rates were analyzed using the Kaplan-Meier method and Cox regression models. RESULTS: In patients undergoing PS and CCRT, OS rates were 45.0% and 33.1% (p < 0.001), respectively, and DFS rates were 36.2% and 28.9% (p = 0.003), respectively. In subgroup analysis, in patients with stage IVA HPSCC, PS was associated with higher OS rate (p = 0.002), particularly in those with T4 or N2 classification (p = 0.021 and 0.002, respectively). Multivariate analysis indicated that stage IVA HPSCC, stage IVB HPSCC, and CCRT were independent adverse prognostic factors for OS rate (p = 0.004, < 0.001, and 0.014, respectively). Furthermore, in patients with stage IVA HPSCC aged ≥ 65 years and with N2 classification, CCRT was significantly associated with lower OS rates than was PS (p = 0.027 and 0.010, respectively). CONCLUSIONS: In patients with advanced HPSCC, PS was significantly associated with better prognosis than CCRT. PS could be a favorable primary treatment modality for the management of patients with stage IVA HPSCC, particularly those aged ≥ 65 years and with T4 and N2 classification.
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Quimioradioterapia/estadística & datos numéricos , Neoplasias Hipofaríngeas/terapia , Faringectomía/estadística & datos numéricos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Factores de Edad , Anciano , Toma de Decisiones Clínicas , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hipofaríngeas/mortalidad , Neoplasias Hipofaríngeas/patología , Hipofaringe/patología , Hipofaringe/cirugía , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Selección de Paciente , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been reported to be both a prognostic biomarker for cancer and associated with inflammation, but its predictive role in tumor immunity is not clear. The present study examined the correlations of the NLR and immune suppression with the prognoses in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We performed a retrospective review of 1168 patients who were newly diagnosed with stage T1N(+) and T2-T4 ESCC at our hospital. The NLR of each ESCC patient prior to treatment was calculated, and the associations of the NLR with various clinicopathological parameters and prognoses were then examined. In addition, correlations of the proportion of myeloid-derived suppressor cells (MDSCs) and level of interleukin (IL)-6 with the NLR were assessed in 242 ESCC patients. RESULTS: An elevated NLR was significantly correlated with advanced-stage disease and reduced overall survival (OS) of ESCC patients. Furthermore, the levels of IL-6 in tumors and MDSCs in the peripheral circulation were significantly correlated with the prognoses of ESCC, and the NLR was positively correlated with MDSC levels in the circulation and IL-6 staining intensity in tumor specimens. Moreover, a high NLR was significantly associated with reduced OS in the 926 patients treated with concomitant chemoradiotherapy, but not in the 242 patients who underwent surgical intervention. CONCLUSION: The NLR may represent a clinically useful biomarker to guide ESCC treatment decisions. Patients with a higher NLR may be an optimal subgroup for IL-6- and MDSC-targeted therapy.
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Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/patología , Quimioradioterapia/mortalidad , Neoplasias Esofágicas/patología , Linfocitos/patología , Recurrencia Local de Neoplasia/patología , Neutrófilos/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/terapia , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
We explored the effects of various parameters on taste impairments (TIs) in head-and-neck (H&N) cancer patients receiving intensity-modulated radiotherapy (IMRT). From January 2014 to September 2017, 88 H&N cancer patients subjected to curative or postoperative IMRT were enrolled in this prospective study. All patients underwent at least 1 year of follow-up after IMRT. Quality-of-life assessments in terms of patient-reported gustatory function were measured using the taste-related questions of the European Organization for Research and Treatment of Cancer H&N35 questionnaires. At a median follow-up time of 27 months, 27 of 88 patients (30.7%) reported long-term TIs. In multivariate analyses, glossectomy most significantly predicted TIs (P = 0.04). The percentage of TIs (61.5%) was significantly (P = 0.03) higher in patients who underwent partial or total glossectomy than in patients who did not undergo surgery (28.0%) and those who underwent radical surgery without glossectomy (20.0%). When we excluded surgical patients from analyses, the mean radiation dose to the oral cavity was of borderline significance in terms of TI prediction (P = 0.05). Only 10.5% of patients suffered from TIs when the mean radiation dose was <5000 cGy compared with 38.7% when the mean dose was ≥5000 cGy. In conclusion, glossectomy is the major cause of long-term TIs in H&N cancer patients receiving IMRT. In patients who do not undergo glossectomy, reduction of the mean radiation dose to the oral cavity may reduce TIs after IMRT.
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Glosectomía/efectos adversos , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Boca/cirugía , Radioterapia de Intensidad Modulada/efectos adversos , Trastornos del Gusto/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Calidad de Vida , Dosis de Radiación , Adulto JovenRESUMEN
OBJECTIVE: To study the impacts of aluminum chloride (AlCl3) on the sperm quality, sperm mitochondrial membrane potential (MMP) and sperm mitochondrial membrane permeability transition pore (MPTP) function of male rats, and the possible mechanisms of AlCl3 inducing the declination of sperm quality. METHODS: According to the median lethal dose (LD50) of AlCl3ã»6H2O in drinking water, we randomly assigned 96 male Wistar rats weighing 180ï¼200 g to four groups of equal number and fed them with AlCl3 aqueous drinking water at 256.72 mg/kg/d (1/5 LD50, high-dose group), 128.36 mg/kg/d (1/10 LD50, medium-dose group), 64.18 mg/kg/d (1/20 LD50, low-dose group) and 0 mg/kg/d (control group), respectively, all for 16 weeks. Then, we examined the quality of the epididymal sperm of the rats, observed the morphology of the sperm mitochondria under the transmission electron microscope, and determined the MMP level of the sperm mitochondria and the function of the MPTP by flow cytometry. RESULTS: The percentage of progressively motile sperm was significantly decreased in the low-, medium- and high-dose AlCl3 groups as compared with that in the control group (ï¼»46.49 ± 5.37ï¼½%, ï¼»33.50 ± 8.75ï¼½% and ï¼»16.94 ± 5.00ï¼½% vs ï¼»66.28 ± 5.68ï¼½%, P < 0.01), that of dead sperm was remarkably increased (ï¼»19.73 ± 5.57ï¼½%, ï¼»35.80 ± 5.90ï¼½% and ï¼»55.19 ± 4.97ï¼½% vs ï¼»12.71 ± 4.84ï¼½%, P < 0.01), and so was that of morphologically abnormal sperm (ï¼»19.06 ± 2.44ï¼½%, ï¼»23.78 ± 3.29ï¼½% and ï¼»32.06 ± 4.65ï¼½% vs ï¼»14.56 ± 1.62ï¼½%, P < 0.01). Sperm mitochondrial swelling was aggravated in the AlCl3-exposed rats in a dose-dependent manner. The sperm MMP level was significantly lower in the low-, medium- and high-dose AlCl3 groups than in the control (ï¼»60.88 ± 7.37ï¼½%, ï¼»51.54 ± 6.12ï¼½% and ï¼»37.70 ± 7.44ï¼½% vs ï¼»74.35±4.67ï¼½%, P < 0.01), with a negative correlation to the dose of AlCl3 (rs = ï¼0.819, P < 0.01), while the pathologically open MPTP was markedly higher in the former three than in the latter group (ï¼»27.80 ± 5.74ï¼½%, ï¼»36.58 ± 6.67ï¼½% and ï¼»64.95 ± 8.07ï¼½% vs ï¼»15.37 ± 7.13ï¼½%, P < 0.01), with a positive correlation to the dose of AlCl3 (rs = 0.867, P < 0.01). CONCLUSIONS: Exposure to aluminum can cause sperm mitochondrial swelling, decrease the sperm MMP level, induce pathological opening of the MPTP, and consequently reduce sperm quality in male rats.
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Aluminio/toxicidad , Mitocondrias/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Animales , Epidídimo , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Microscopía Electrónica de Transmisión , Mitocondrias/ultraestructura , Proteínas de Transporte de Membrana Mitocondrial/efectos de los fármacos , Poro de Transición de la Permeabilidad Mitocondrial , Distribución Aleatoria , Ratas , Ratas Wistar , Espermatozoides/ultraestructuraRESUMEN
Developing red thermally activated delayed fluorescence (TADF) emitters, attainable for both high-efficient red organic light-emitting diodes (OLEDs) and non-doped deep red/near-infrared (NIR) OLEDs, is challenging. Now, two red emitters, BPPZ-PXZ and mDPBPZ-PXZ, with twisted donor-acceptor structures were designed and synthesized to study molecular design strategies of high-efficiency red TADF emitters. BPPZ-PXZ employs the strictest molecular restrictions to suppress energy loss and realizes red emission with a photoluminescence quantum yield (ΦPL ) of 100±0.8 % and external quantum efficiency (EQE) of 25.2 % in a doped OLED. Its non-doped OLED has an EQE of 2.5 % owing to unavoidable intermolecular π-π interactions. mDPBPZ-PXZ releases two pyridine substituents from its fused acceptor moiety. Although mDPBPZ-PXZ realizes a lower EQE of 21.7 % in the doped OLED, its non-doped device shows a superior EQE of 5.2 % with a deep red/NIR emission at peak of 680â nm.
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Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and significantly increased in cancer stem-like cells. In the present study, the role of ALDH1 in esophageal squamous cell carcinoma (ESCC) was investigated. We retrospectively analyzed the clinical outcomes of 148 ESCC and examined its correlation with ALDH1 levels. Furthermore, we preformed cellular and animal experiments to investigate the role of ALDH1 in tumor progression and microenvironment. Our data revealed that ALDH1 staining was positively linked to a higher clinical stage, higher loco-regional failure rate, and shorter survival time. Furthermore, there was a positive link between ALDH1 expression and IL-6 signaling according to the data of clinical specimens and cellular experiments. Using animal model, ALDH1-positive tumors were associated with aggressive tumor growth, increased IL-6, augmented epithelial-mesenchymal transition (EMT), and activation of myeloid-derived suppressor cells (MDSCs). Blockade of COX-2 attenuated the aggressive tumor growth of ALDH1-positive cancer cells. In conclusion, our findings suggested that ALDH1 played an important role in tumor aggressiveness and associated with a tumor-promoting microenvironment in esophageal cancer. Directly targeting ALDH1 or using a COX-2 inhibitor could be a promising strategy for the treatment of ESCC.
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Carcinoma de Células Escamosas/enzimología , Neoplasias Esofágicas/enzimología , Isoenzimas/metabolismo , Retinal-Deshidrogenasa/metabolismo , Microambiente Tumoral , Adulto , Anciano , Anciano de 80 o más Años , Familia de Aldehído Deshidrogenasa 1 , Animales , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Inhibidores de la Ciclooxigenasa/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Humanos , Interleucina-6/metabolismo , Masculino , Ratones Desnudos , Persona de Mediana Edad , Nitrobencenos/farmacología , Pronóstico , Estudios Retrospectivos , Sulfonamidas/farmacología , Análisis de Supervivencia , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: CD44, a cancer stem cell surface marker, is associated with treatment resistance and prognosis in some cancers. In the present study, we examined the predictive value of CD44 in muscle-invasive bladder cancer (MIBC). METHODS: We retrospectively analyzed the clinical outcomes of 105 MIBC patients and correlated these outcomes with the expression of CD44. Furthermore, the bladder cancer cell lines HT1197 and MB49 were selected for cellular and animal experiments to investigate the correlation between CD44 and tumor aggressiveness. RESULTS: Analysis of clinical specimens indicated that CD44 staining was significantly associated with a higher clinical stage, higher locoregional failure rate, and lower disease-specific survival rate for MIBC patients. Using cellular experiments and orthotopic tumor models, we showed that CD44+ bladder cancer cells had a higher invasion ability and augmented epithelial-mesenchymal transition (EMT) compared with CD44 cells. There was a significant correlation between interleukin (IL)-6 and CD44 levels noted by in vitro testing, and clinical samples. Blockade of IL-6 attenuated the expression of CD44, cancer stem-cell-like properties, and aggressive tumor behavior in vitro and in vivo. The related changes included the attenuated STAT3 activation and EMT, and decreased programmed death ligand 1-mediated T-cell suppression. CONCLUSION: Our findings suggest that CD44 expression is positively associated with tumor aggressiveness in bladder cancer, and activated IL-6 signaling provides a suitable microenvironment for the induction of CD44 expression.
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Biomarcadores de Tumor/metabolismo , Transición Epitelial-Mesenquimal , Receptores de Hialuranos/metabolismo , Interleucina-6/metabolismo , Neoplasias de los Músculos/secundario , Recurrencia Local de Neoplasia/patología , Neoplasias de la Vejiga Urinaria/patología , Anciano , Anciano de 80 o más Años , Animales , Apoptosis , Movimiento Celular , Proliferación Celular , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Neoplasias de los Músculos/metabolismo , Neoplasias de los Músculos/cirugía , Invasividad Neoplásica , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/cirugía , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Pronóstico , Transducción de Señal , Tasa de Supervivencia , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/cirugía , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Multifunctional emitting materials are scarce and need to be further explored. Now, a newly anthraquinone derivative, 2-(phenothiazine-10-yl)-anthraquinone (PTZ-AQ) was designed and synthesized and found to demonstrate polymorphism, multi-color emission, aggregation-induced emission (AIE), mechanochromic luminescence (MCL), and thermally activated delayed fluorescence (TADF) in its different solid forms. It is shown for the first time that TADF properties of a compound can be systematically tuned via its aggregation state. The optimized PTZ-AQ crystal shows a small singlet-triplet energy splitting of 0.01â eV and exhibits red TADF with a photoluminescence quantum yield as high as 0.848. This study shows that the unique multiple functions can be integrated into one single compound through controlling the aggregation states, which provides a new strategy for the investigation and application of multifunctional organic materials.
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BACKGROUND: The National Comprehensive Cancer Network guidelines recommend that patients with oral cavity squamous cell carcinoma (OSCC) and cT4b disease should be either included in clinical trials or treated with a nonsurgical approach. However, surgery may be feasible in selected patients with adequate safety margins. Using the nationwide Taiwanese Cancer Registry Database, we examined the prognosis of cT4b OSCC patients in relation to their treatment approach. METHODS: Of the 18,910 patients with previously untreated first primary OSCC identified between 2004 and 2010, 492 (2.6 %) had cT4b tumors. Of them, 327 (66 %) received initial treatment with surgery, whereas 165 (34 %) were initially treated with a nonsurgical approach. Of the latter group, 78 patients subsequently underwent surgery. A 5-year disease-specific survival (DSS) ≥45 % was considered as a favorable outcome. RESULTS: Better 5-year DSS and overall survival (OS) rates were observed in cT4b patients initially treated with surgery (vs. nonsurgery; DSS, 51 vs. 38 %; OS, 43 vs. 27 %, respectively, p < 0.001). Of the participants initially treated with surgery, patients with cN0-2 disease had better 5-year survival rates (DSS: cN0, 59 %; cN1, 53 %; cN2, 46 %; OS: cN0, 49 %; cN1, 50 %; cN2, 37 %) than those with cN3 disease (DSS: 0 %; OS: 0 %). Among cT4b patients who initially received a nonsurgical treatment, subjects who subsequently underwent surgery showed better outcomes. CONCLUSIONS: Primary surgery is performed in approximately two-thirds of cT4b OSCC patients, with cN0-2 cases showing a good prognosis. Patients who initially received a nonsurgical approach can subsequently be treated with surgery and achieve favorable outcomes.
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Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/terapia , Neoplasias de la Boca/patología , Neoplasias de la Boca/terapia , Adulto , Anciano , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/cirugía , Terapia Combinada , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/cirugía , Estadificación de Neoplasias , Pronóstico , Radioterapia , Tasa de Supervivencia , TaiwánRESUMEN
Mechanisms of charge transport between the interconnector and its neighboring layers in tandem organic photovoltaic cells have been systematically investigated by studying electronic properties of the involving interfaces with photoelectron spectroscopies and performance of the corresponding devices. The results show that charge recombination occurs at HATCN and its neighboring hole transport layers which can be deposited at low temperature. The hole transport layer plays an equal role to the interconnector itself. These insights provide guidance for the identification of new materials and the device architecture for high performance devices.
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An attempt to maintain the three-dimensional space into restorative sites through the conveniently pack porous fillers are general used strategy. Advancement in the manufacturing protective shells in the scaffolds, which would be filled with brittle ceramic grafts for the development of highly connective pores provides the approach to solve crack problem for generating the tissues. Therefore, multilayered braided and alkalized poly(lactic acid) (PLA) composites with calcium phosphate bone cement (CPC) were synthesized and compared. The PLA/CPC composites were divided into various groups according to a series of heat-treatment temperatures (100-190 °C) and periods (1-3 h) and then characterized. The effects of 24-h immersion on the strength decay resistance of the samples were compared. Results showed that the residual oil capped on the surfaces of alkalized PLA braid was removed, and the structure was unaltered. However, the reduced tensile stress of alkalized PLA braids was due to ester-group formation by hydrolysis. Mechanical test results of PLA/CPC composites showed that the strength significantly increased after heat treatment, except when the heating temperature was higher than the PLA melting point at approximately 160-170 °C. The degree of PLA after recrystallization became higher than that of unheated composites, thereby leading to reduced strength and toughness of the specimen. Braiding fibers of biodegradable PLA reinforced and toughened the structure particularly of the extra-brittle material of thin-sheet CPC after implantation.
Asunto(s)
Cementos para Huesos , Sustitutos de Huesos/química , Ácido Láctico , Ensayo de Materiales , Polímeros , Fosfatos de Calcio , Cerámica , PoliésteresRESUMEN
BACKGROUND & AIMS: Several animal studies have shown that statins can inhibit the progression of cirrhosis; however, few clinical studies have been conducted. Previous studies have indicated that statins can prevent the progression of hepatic fibrosis in patients with hepatitis C virus (HCV) infection and advanced hepatic fibrosis, however data is lacking on patients who have yet to progress to cirrhosis. This study investigated the association between the use of statin and the risk of cirrhosis development in patients with HCV infection. METHODS: We conducted a population-based cohort study by using the Taiwan National Health Insurance Research Database. A total of 226,856 patients with HCV infection were included as the study cohort. Each patient was followed from 1997 to 2010 to identify incident cases of cirrhosis. A Cox proportional hazard regression was performed to evaluate the association between statin use and cirrhosis risk. RESULTS: A total of 34,273 cases of cirrhosis were identified in the cohort with HCV infection during the follow-up period of 2,874,031.7 person-years. The incidence rate was 445.5 cases of cirrhosis per 100,000 person-years (95% confidence interval (CI), 423.3 to 465.7) for statin users (defined as those who used more than 28 cumulative defined daily doses (cDDD)), and 1311.2 cirrhosis cases per 100,000 person-years (95% CI, 1297.1 to 1325.6) for non-users. A dose-response relationship between statin use and cirrhosis risk was observed. The adjusted hazard ratios were 0.33 (95% CI, 0.31 to 0.36), 0.24 (95% CI, 0.22 to 0.25), and 0.13 (95% CI, 0.12 to 0.15) for statin use of 28 to 83, 84 to 365, and more than 365 cDDD, respectively, relative to no statin use (<28 cDDD). CONCLUSION: Among the patients with HCV infection, statin use was associated with a reduced risk of cirrhosis development in a dose-dependent manner. Further clinical research is required.