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Urinary cell-free DNA (ucfDNA) is a potential biomarker for bladder cancer detection. However, the biological characteristics of ucfDNA are not well understood. We explored the roles of deoxyribonuclease 1 (DNASE1) and deoxyribonuclease 1-like 3 (DNASE1L3) in the fragmentation of ucfDNA using mouse models. The deletion of Dnase1 in mice (Dnase1-/-) caused aberrations in ucfDNA fragmentation, including a 24-fold increase in DNA concentration, and a 3-fold enrichment of long DNA molecules, with a relative decrease of fragments with thymine ends and reduction of jaggedness (i.e., the presence of single-stranded protruding ends). In contrast, such changes were not observed in mice with Dnase1l3 deletion (Dnase1l3-/-). These results suggested that DNASE1 was an important nuclease contributing to the ucfDNA fragmentation. Western blot analysis revealed that the concentration of DNASE1 protein was higher in urine than DNASE1L3. The native-polyacrylamide gel electrophoresis zymogram showed that DNASE1 activity in urine was higher than that in plasma. Furthermore, the proportion of ucfDNA fragment ends within DNase I hypersensitive sites (DHSs) was significantly increased in Dnase1-deficient mice. In humans, patients with bladder cancer had lower proportions of ucfDNA fragment ends within the DHSs when compared with participants without bladder cancer. The area under the curve (AUC) for differentiating patients with and without bladder cancer was 0.83, suggesting the analysis of ucfDNA fragmentation in the DHSs may have potential for bladder cancer detection. This work revealed the intrinsic links between the nucleases in urine and ucfDNA fragmentomics.
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Ácidos Nucleicos Livres , Neoplasias da Bexiga Urinária , Animais , Ácidos Nucleicos Livres/genética , DNA/genética , Desoxirribonuclease I/genética , Desoxirribonuclease I/metabolismo , Endodesoxirribonucleases/genética , Endonucleases , Humanos , Camundongos , Camundongos Knockout , Neoplasias da Bexiga Urinária/genéticaRESUMO
This work reports on the emergence of quantum Griffiths singularity (QGS) associated with the magnetic field induced superconductor-metal transition (SMT) in unconventional Nd_{0.8}Sr_{0.2}NiO_{2} infinite layer superconducting thin films. The system manifests isotropic SMT features under both in-plane and perpendicular magnetic fields. Importantly, after scaling analysis of the isothermal magnetoresistance curves, the obtained effective dynamic critical exponents demonstrate divergent behavior when approaching the zero-temperature critical point B_{c}^{*}, identifying the QGS characteristics. Moreover, the quantum fluctuation associated with the QGS can quantitatively explain the upturn of the upper critical field around zero temperature for both the in-plane and perpendicular magnetic fields in the phase boundary of SMT. These properties indicate that the QGS in the Nd_{0.8}Sr_{0.2}NiO_{2} superconducting thin film is isotropic. Moreover, a higher magnetic field gives rise to a metallic state with the resistance-temperature relation R(T) exhibiting lnT dependence among the 2-10 K range and T^{2} dependence of resistance below 1.5 K, which is significant evidence of Kondo scattering. The interplay between isotropic QGS and Kondo scattering in the unconventional Nd_{0.8}Sr_{0.2}NiO_{2} superconductor can illustrate the important role of rare region in QGS and help to uncover the exotic superconductivity mechanism in this system.
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We designed and synthesized a new Schiff base probe, which incorporated the salicylaldehyde-analogue α-cyanostilbene and benzophenone hydrazone by the imine linkage. Its chemical structure was verified by FT-IR, MALDI-TOF-MS, HR-MS and 1H/13C NMR technologies. It could exhibit a red fluorescence based on the synergistical effects of aggregation-induce emission (AIE), excited-state intramolecular proton transfer (ESIPT) and twisted intramolecular charge-transfer (TICT) in the aggregation or solid states. Interestingly, the TLC-based test strip loaded with the target compound showed the reversible fluorescence response to amine/acid vapor and on-site visual fluorescence quenching response to Fe3+. In THF/water mixtures (fw = 90%, 10 µM, pH = 7.4), the detection limit (DL) and the binding constant (Ka) of the developed probe towards Fe3+ were evaluated as 5.50 × 10- 8 M and 1.69 × 105, respectively. The developed probe was successfully applied for the detection of Fe3+ with practical, reliable, and satisfying results.
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A pair of 1,8-naphthalimides (NPIs) were designed and successfully synthesized through embellishing amino-containing NPI with 4-diethylaminosalicyladehyde and 4-diethylaminobenzaldehyde, respectively. Their structures were fully confirmed by 1H/13C NMR, HR-MS and FT-IR spectroscopic studies. Their photophysical properties were systematically investigated in different solvents of varied polarity, in THF/water mixtures with varying water fractions (fw), and in THF solvent with varying concentrations of NPIs. It inferred that the distinct differences in emission between two NPIs during self-assembled process could be ascribed that the hydroxyl-containing NPI allowed the excited-state intramolecular proton transfer process between -OH and CH=N units in the aggregation state. Interestingly, the solid of 4-diethylaminosalicyladehyde-functionalized NPI exhibited multi-stimuli-responsive fluorescence changes involving mechanofluorochromism and HCl/NH3 vapor stimulus-induced conversion. However, no remarkable change was observed in the photoluminescence (PL) spectra for the solid of 4-diethylaminobenzaldehyde-functionalized NPI under the stimuli of mechanical force and organic solvent.
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Naftalimidas , Naftalimidas/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Estrutura Molecular , Solventes/química , Espectrometria de Fluorescência , FluorescênciaRESUMO
PURPOSE: Language networks are reorganized during glioma growth, leading to varying language performance in patients with gliomas located in or around language-eloquent areas. Therefore, pre-treated language performance reflects the neuroplasticity potential. Different domains of language processing, such as speech expression, repetition, and comprehension, involving different neural networks. We analyzed the effects of patient factors and tumor characteristics on the pre-treated performance to investigate neuroplastic potential of different language domains. METHODS: Patient age, sex, education level, tumor grade, language pathway involvement, T1 contrast enhanced (C+), and FLAIR (T2) volume were selected as variables. The correlation with abnormal language performance was verified using univariate and multivariate logistic regression. RESULTS: In total, 104 left hemispheric glioma patients were enrolled in this study. 44% of patients had repetitive abnormalities, 34.9% had comprehensive abnormalities, and 32.1% had expressive abnormalities. The proportion of normal language performance was 60% in grade 2 and 3 gliomas and 16% in grade 4 gliomas. Tumor grade (p = 0.006) and T2 volume (p = 0.008) were associated with abnormal performance in the expressive domain, education level (p = 0.004) and T1 C+ volume (p = 0.049) in the repetitive domain, and education level (p = 0.013), T2 volume (p = 0.011), and tumor grade (p = 0.089) in the comprehensive domain. CONCLUSION: Different clinical and radiological factors affected the abnormal performance of the three language domains, indicating their functional connectivity and neuroplastic potential are inherently varied. The dynamic interactions between patient factors, tumor characteristics, and language processing should be considered when resecting left hemispheric gliomas.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/patologia , Glioma/patologia , Idioma , Fala , Procedimentos Neurocirúrgicos , Mapeamento EncefálicoRESUMO
Herein, α-cyanostilbene-based luminogen with an electron donor-π-electron acceptor (D-π-A) architecture was formylated into the salicylaldehyde-analogue luminogen, followed by the Schiff base reaction with phenylamine, a red-emitting luminogen was elaborately designed and successfully synthesized in a high yield of 89%. Its well-defined structure was confirmed by FT-IR, MALDI-TOF-MS, HR-MS and 1H/13C NMR technologies. Based on the synergistic mechanisms of aggregation-induced emission (AIE), excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT), it enjoyed a red-fluorescence emission at 627 nm in THF/water mixtures (fw = 95%) and was used as a probe. Moreover, the TLC-based test strips loaded with the probe not only exhibited the reversible fluorescence response to amine/acid vapor but also showed sensitive and selective fluorescence response towards Cu2+. Furthermore, the fluorescence titration experiment between the probe and Cu2+ in THF/water mixtures (fw = 95%, pH = 7.4) revealed that the detection limit was 1.18 × 10-7 M and the binding constant was 1.59 × 105. Job's plot experiment and HR-MS analysis revealed the 2:1 binding stoichiometry of the probe with Cu2+. The method enabled real-time assessment for Cu2+ in real water samples. This study could offer insightful opinions on the development of long-wavelength emissive luminogens based on α-cyanostilbene.
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Swallowing function can deteriorate with age, leading to a risk of dysphagia. Swallowing evaluation by surface electromyography (sEMG) can be easily and extensively applied for an elderly population. This study evaluated the temporal events observed by sEMG to clarify how aging affects the coordination among the masticatory and suprahyoid muscles. We recruited elderly individuals (over 65 years old) who denied dysphagia. The sEMG activities of anterior temporalis, masseter, and suprahyoid muscles were recorded during 3, 15, and 30 ml water swallowing tests (WST). We calculated the time interval between anterior temporalis and suprahyoid peak activity (T-SH interval) and masseter and suprahyoid peak activity (M-SH interval) and analyzed their correlation with age. The subjects who could and could not swallow 30 ml of water in one gulp were further assigned into the one-gulp and piecemeal groups, respectively, for subgroup analysis. We recruited 101 subjects, among whom 75 (26 males and 49 females) were analyzed after excluding those with suspected dysphagia or low-quality sEMG recordings. Age was significantly correlated with the bilateral T-SH (left: r = 0.249, p = 0.031; right: r = 0.412, p < 0.01) and right M-SH (r = 0.242, p = 0.037) intervals in the 30 ml WST. The correlation between intervals and age were observed in both subgroups. sEMG can be used to investigate the effect of aging on the temporal coordination between masticatory and suprahyoid contraction. Further studies are needed to verify the validity of screening subclinical dysphagia in the elderly.
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Transtornos de Deglutição , Deglutição , Masculino , Feminino , Humanos , Idoso , Eletromiografia , Deglutição/fisiologia , Transtornos de Deglutição/diagnóstico , Músculos do Pescoço/fisiologia , EnvelhecimentoRESUMO
Analysis of nonlinear dynamic characteristics of cardiac systems has been a hot topic of clinical research, and the recurrence plots have earned much attention as an effective tool for it. In this paper, we propose a novel method of multivariate joint order recurrence networks (MJORNs) to evaluate the multi-lead electrocardiography (ECG) time series with healthy and psychological heart states. The similarity between time series is studied by quantifying the structure in a joint order pattern recurrence plot. We take the time series that corresponds to each of the 12-lead ECG signals as a node in the network and use the entropy of diagonal line length that describes the complex structure of joint order pattern recurrence plot as the weight to construct MJORN. The analysis of network topology reveals differences in nonlinear complexity for healthy and heart diseased heartbeat systems. Experimental outcomes show that the values of average weighted path length are reduced in MJORN constructed from crowds with heart diseases, compared to those from healthy individuals, and the results of the average weighted clustering coefficient are the opposite. Due to the impaired cardiac fractal-like structures, the similarity between different leads of ECG is reduced, leading to a decrease in the nonlinear complexity of the cardiac system. The topological changes of MJORN reflect, to some extent, modifications in the nonlinear dynamics of the cardiac system from healthy to diseased conditions. Compared to multivariate cross recurrence networks and multivariate joint recurrence networks, our results suggest that MJORN performs better in discriminating healthy and pathological heartbeat dynamics.
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Eletrocardiografia , Dinâmica não Linear , Humanos , Frequência Cardíaca , Fatores de Tempo , Eletrocardiografia/métodos , EntropiaRESUMO
BACKGROUND: Improving chewing function of older adults increases the health-related quality of life. Few studies indicated the correlation between tongue, lip strength on masticatory performance in older people. The study aimed to investigate the association between lip, tongue strength on chewing pattern in aging population. METHODS: The older adults had independent daily intake without assistance were enrolled. They had intact dentition and no periodontitis. To estimate the number of chewing strokes and chewing time by consuming a cornstarch cookie were used to represent chewing pattern. Lip and tongue pressure were evaluated with an Iowa Oral Performance Instrument. Linear regression analysis was used to analyze the lip and tongue pressure associated with the chewing time and strokes. Spearman's correlation analysis was utilized to evaluate the associations among chewing time and chewing strokes or lip and tongue pressure. RESULTS: 35 women and 35 men with an average age of 73.2 years were investigated. Tongue pressure was significantly related to the chewing time and the number of chewing strokes (p = 0.01 and 0.03). There was a close association between chewing time and the number of chewing strokes (p < 0.0001). The correlation between lip and tongue pressure was significant (p < 0.0001). CONCLUSION: The tongue strength significantly related to chewing ability in aging population. Increasing the tongue strength greatly reduced the number of chewing strokes and chewing time. Good masticatory ability could increase the motor function of tongue; raising the tongue strength might be able to improve mastication in older adults.
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Mastigação , Língua , Masculino , Humanos , Feminino , Idoso , Lábio , Pressão , Qualidade de Vida , EnvelhecimentoRESUMO
Here, three Schiff bases 3a-c, differing by the substitutions (-H, -Cl, and -N(CH3)2) on the phenyl ring, have been designed and synthesized via the reaction of ortho-aminophenol with benzaldehyde, 2,4-dichlorobenzaldehyde and para-dimethylamine benzaldehyde in 1:1 molar ratio with favourable yields of 89-92%, respectively. Their structural characterizations were studied by FT-IR, NMR, MALDI-MS and elemental analysis. The fluorescence behaviours of compounds 3a and 3b exhibited a severe aggregation caused quenching (ACQ) effect in EtOH/water system. On the contrary, compound 3c had an obvious J-aggregation induced emission (AIE) feature in EtOH/water mixture (v/v = 1:1), and exhibited excellent sensitivity and anti-interference towards Cu2+ with the limit of detection (LOD) of 1.35 × 10-8 M. Job's plot analysis and MS spectroscopic study revealed the 2:1 complexation of probe 3c and Cu2+. In addition, probe 3c was successfully applied to the determination of Cu2+ in real aqueous samples.
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AIMS AND OBJECTIVES: To explore whether dual-lumen power injectable peripherally inserted central catheters (PICCs) could be effectively and safely applied in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and for serum cyclosporine level monitoring. BACKGROUND: Compared to conventional central venous access devices, PICC provides a feasible route not only for fluid infusion, but also for blood sample collection in patients undergoing oncological treatments. DESIGN: A prospective observational study was conducted according to the STROBE guidelines. METHODS: We prospectively evaluated the applications and complications of power injectable PICCs in 52 consecutive allo-HSCT recipients. We also compared the cyclosporine levels in 188 paired blood samples, simultaneously obtained via power injectable PICCs and percutaneous venous puncture, to investigate whether power injectable PICC is a feasible route for cyclosporine concentration monitoring in allo-HSCT. RESULTS: The median PICC placement duration was 29 days. The insertion-site blood oozing and central line-associated bloodstream infection rates were 36.5% (19/52) and 26.9% (14/52), respectively, indicating the feasibility of these PICCs for various applications in allo-HSCT. No power injectable PICC-related thrombotic adverse events were identified; 90.4% (47/52) of cases with power injectable PICC removal occurred because of lack of medical utility, suggesting that power injectable PICC-related complications were manageable. However, cyclosporine levels in samples obtained via these PICCs were significantly higher than those in samples obtained via percutaneous venous puncture (261.5 ± 139.2 vs. 232.4 ± 253.6 ng/ml; p = 0.019 [set 1]; 254.8 ± 89.3 vs. 225.1 ± 233.3 ng/ml; p<0.001 [set 2]; 283.6 ± 103.9 vs. 238.0 ± 254.7 ng/ml; p = 0.006 [set 3]; 291.0 ± 94.9 vs. 266.0 ± 274.7 ng/ml; p = 0.016 [set 4]). CONCLUSION: The power injectable PICC is a feasible venous access device for allo-HSCT. RELEVANCE TO CLINICAL PRACTICE: The dual-lumen power injectable PICCs provided a reliable access for blood sample collection, decreasing the number of blind percutaneous venous punctures in allo-HSCT. However, its application in cyclosporine level monitoring needs further investigation.
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Cateterismo Venoso Central , Cateterismo Periférico , Cateteres Venosos Centrais , Ciclosporinas , Transplante de Células-Tronco Hematopoéticas , Catéteres , Humanos , Fatores de RiscoRESUMO
A novel fluorescein-bridged perylene bisimide (PBI) dimer for liquid crystal (LC) with geometrically symmetric structure was developed. The mesomorphic results indicated that the energetically stable and unstable conformers of fluorescein fragments could lead to the transformation of mesophases from a hexagonal columnar mesophase to an uncertain phase at 136.9 °C in heating, whilst a stable hexagonal columnar mesophase maintained between 175.6 °C and 58.6 °C in cooling. The selectively excited fluorescence characters in THF solution demonstrated that the fluorescence resonance energy transfer (FRET) effect between fluorescein fragments and PBI unites could provide a means to effectively impose strong fluorescence of the dimeric PBIs modified with suitable chromophore at the N-imide position, which alternatively serves as a platform for the further study of multi-functional PBI-based LCs.
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By tactfully structuring a luminescent molecule as an accurate pH probe with aggregation-induced emission (AIE) feature, it is significant to overcome aggregation-caused quenching of emitted light in practice. Herein, we present a simple AIE-active fluorescence probe for pH detection on the basis of intramolecular charge transfer (ICT) with wide response range and high sensitivity reaction. The donor-acceptor-donor (D-A-D) style probe utilized a conjugated structural hybrid of the electron-withdrawing nitrile group and electron-donating hydroxyl as well as dimethylamino groups for fluorescent platform. The AIE-active probe possesses good fluorescence under water fraction up to 90% in mixed MeOH/water system. Furthermore, it can be used in profiling and visualization of pH detection in MeOH/water system at fw = 90% under UV 365 nm lamp. What's more, the probe can be employed to be a broad range test paper of pH detection, paving the way for low-cost practical applications.
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AIM: To explore the effect of miR-296-5p on the metastasis of nasopharyngeal carcinoma (NPC) cells and investigate the underlying mechanism. METHODS: The expressions of miR-296-5p in NPC tissues and cells were determined using GSE32920 database analysis and real-time PCR and miRNA microarray assays. An miR-296-5p mimic and inhibitor were transfected into NPC cells. Then, immunofluorescence imaging, scratch wound-healing, transwell migration and invasion assays were used to observe the effects of miR-296-5p on cell metastasis and invasion. Real-time PCR and western blotting were carried out to detect the expressions of genes and proteins related to epithelial-mesenchymal transition (EMT). A dual luciferase reporter assay was used to identify whether TGF-ß is the target gene of miR-296-5p. Finally, TGF-ß expression plasmids were transfected into NPC cells to verify the role of TGF-ß in the miR-296-5p-mediated inhibition of nasopharyngeal carcinoma cell metastasis. RESULTS: Our results show that miR-296-5p inhibits the migratory and invasive capacities of NPC cells by targeting TGF-ß, which suppresses EMT. Importantly, the miR-296-5p level was significantly lower in human NPC tissues than in adjacent normal tissues. It also negatively correlated with TGF-ß and was significantly associated with the lymph node metastasis of patients with NPC. CONCLUSIONS: Our findings show that miR-296-5p represses the EMT-related metastasis of NPC by targeting TGF-ß. This provides new insight into the role of miR-296-5p in regulating NPC metastasis and invasiveness.
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Transição Epitelial-Mesenquimal/genética , MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Invasividade Neoplásica/genética , Fator de Crescimento Transformador beta/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica/patologiaRESUMO
Hepatic veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). We conducted this study to investigate the incidence and risk factors of hepatic VOD for patients receiving HSCT in Taiwan. We retrospectively analyzed the data from a nationwide registry for patients receiving HSCT, which was collected by the Taiwan Society of Blood and Marrow Transplantation. The data collection period was from 2009 to 2014. A total 2345 patients were reviewed and 39 patients among them were diagnosed as having hepatic VOD. The cumulative incidence of hepatic VOD in the whole cohort of 2345 patients was 1.66%. In multivariate analysis, disease diagnosis of myelodysplastic syndrome, chronic HCV infection, condition regimens of bulsulfan intravenously administered, and antithymocyte immunoglobulin were independent factors to predict higher risk of hepatic VOD. The overall mortality rate for patients with hepatic VOD was 79%. Patients with hepatic VOD had significant worse survival outcomes when compared with those without hepatic VOD (P = 0.00063). In conclusion, although the incidence is low, hepatic VOD remains a serious complication after HSCT in Taiwan. The findings of this study could be the basis for developing prophylactic or early treatment strategies for hepatic VOD.
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Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/mortalidade , Sistema de Registros , Adolescente , Adulto , Aloenxertos , Soro Antilinfocitário/administração & dosagem , Soro Antilinfocitário/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Fatores de Risco , Taxa de Sobrevida , Taiwan/epidemiologiaRESUMO
INTRODUCTION: Awake craniotomy pursues a balance between extensive tumor resection and preservation of postoperative language function. A dilemma exists in patients whose tumor resection is restricted due to signs of language impairment observed during awake craniotomy. In order to determine the degree to which recovery of language function caused by tumor resection can be achieved by spontaneous neuroplasticity, the change in postoperative language function was compared to quantified intraoperative linguistic performance. METHODS: The modified, short-form Boston Diagnostic Aphasia Examination (sfBDAE) was used to assess pre- and postoperative language functions; visual object naming (DO 80) and semantic-association (Pyramid and Palm Tree Test, PPTT) tests assessed intraoperative linguistic performance. DO 80 and PPTT were performed alternatively during subcortical functional monitoring while performing tumor resection and sfBDAE was assessed 1-week postoperatively. RESULTS: Most patients with observed language impairment during awake surgery showed improved language function postoperatively. Both intraoperative DO 80 and PPTT showed significant correlation to postoperative sfBDAE domain scores (p < 0.05), with a higher correlation observed with PPTT. A linear regression model showed that only PPTT predicted the postoperative sfBDAE domain scores with the adjusted R2 ranging from 0.51 to 0.89 (all p < 0.01). Receiver operating characteristic analysis showed a cutoff value of PPTT that yielded a sensitivity of 80% and specificity of 100%. CONCLUSION: PPTT may be a feasible tool for intraoperative linguistic evaluation that can predict postoperative language outcomes. Further studies are needed to determine the extent of tumor resection that optimizes the postoperative language following neuroplasticity.
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Encéfalo/cirurgia , Craniotomia , Transtornos da Linguagem/diagnóstico , Transtornos da Linguagem/etiologia , Monitorização Intraoperatória , Complicações Pós-Operatórias/diagnóstico , Adulto , Idoso , Mapeamento Encefálico , Neoplasias Encefálicas/cirurgia , Feminino , Humanos , Testes de Linguagem , Linguística , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Vigília , Adulto JovemRESUMO
A novel perylene bisimide (PBI) derivative with an AIE-active diphenylacrylonitrile unit positioned at the terminal N-imide position through a flexible spacer has been synthesized and characterized. The DSC, POM and XRD studies confirmed that it could self-assemble into a stable hexagonal columnar liquid-crystalline phase between 56 °C and 160 °C. This PBI derivative also exhibited strong fluorescence in solution, thin film and mesophase based on the cooperative mechanism of AIE and FRET between the diphenylacrylonitrile group and perylene moiety. The pseudo Stokes shift was as large as 283 nm, and the fluorescence quantum yields were as high as 0.62-0.79 in solution and 0.68-0.86 in solid state. This study provides a good strategy for converting the columnar liquid crystal with ACQ effect to one with the AIE effect, successfully filling the gap between the excellent columnar mesomorphic properties and strong fluorescence in solid state.
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PURPOSE: Chemokine (C-C Motif) Ligand 18 (CCL18) is a chemotactic cytokine involved in the pathogenesis and progression of various cancers by activating downstream signaling pathways and affecting cellular behaviors. We conducted a meta-analysis to evaluate the CCL18 as a prognostic marker for cancer and determine the relationship between CCL18 and clinicopathological features of cancer. METHODS: We searched the PubMed, Cochrane, Embase, Web of Science and SinoMed databases for publications to investigate the association between CCL18 expression and survival outcome in cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) of overall survival (OS) were pooled. Odds ratios (ORs) of clinicopathological features were computed. Meta-analysis was performed using STATA 12.0 software. RESULTS: Our meta-analysis identified a total of 17 studies including 2829 cases. Meta-analysis revealed that the expression of CCL18 in various cancer tissues was significantly higher than that in the normal group (OR=16.694, 95% CI=14.117-27.476, p<0.01, random effects). The abnormal expression of CCL18 was associated with lymph node metastasis (OR=4.409, 95% CI=2.129-9.128, p<0.01, random effects) and TNM stage (breast cancer subgroup: III+IV vs I+II OR=13.187, 95% CI=8.417-20.660, p<0.01; gastric cancer subgroup: III+IV vs I+II OR=0.034, 95% CI=0.008-0.137, p<0.01) but is was not related to gender (male vs. female: OR=0.88, 95% CI=0.667-1.162, p=0.368) and age (>60 vs. ≤60 years: OR=1.118, 95% CI=0.795-1.571, p-0.522). CCL18 overexpression was associated with poor overall prognosis of breast cancer (Hazard Ratio/HR=2.969, 95% CI=1.361- 6.478, p<0.01, random effects). CONCLUSIONS: CCL18 is highly expressed in cancer tissues and is closely related to tumor metastasis and prognosis, and its role in tumor development is worth of further study.
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Quimiocinas CC/genética , Quimiocinas CC/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Progressão da Doença , Humanos , Imuno-Histoquímica , Neoplasias/patologia , PrognósticoRESUMO
Amounting evidences demonstrated that Rho/Rho-associated kinase (ROCK) might be a novel target for the therapy of Parkinson's disease (PD). Recently, we synthesized L-F001 and revealed it was a potent ROCK inhibitor with multifunctional effects. Here we investigated the effects of L-F001 in PD models. We found that L-F001 potently attenuated 6-OHDA-induced cytotoxicity in PC12 cells and significantly decreased intracellular reactive oxygen species (ROS), prevented the 6-OHDA-induced decline of mitochondrial membrane potential and intracellular GSH levels. In addition, L-F001 increased Akt and GSK-3beta phosphorylation and induced the nuclear Nrf2 and HO-1 expression in a time- and concentration-dependent manner. Moreover, L-F001 restored the levels of p-Akt and p-GSK-3beta (Ser9) as well as HO-1 expression reduced by 6-OHDA. Those effects were blocked by the specific PI3K inhibitor, LY294002, indicating the involvement of Akt/GSK-3beta pathway in the neuroprotective effect of L-F001. In addition, L-F001 significantly attenuated the tyrosinehydroxylase immunoreactive cell loss in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced mice PD model. Together, our findings suggest that L-F001 prevents 6-OHDA-induced cell death through activating Akt/GSK-3beta and Nrf2/HO-1 signaling pathway and attenuates MPTP-induced dopaminergic neuron toxicity in mice. L-F001 might be a promising drug candidate for PD.
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Azepinas/farmacologia , Neurônios Dopaminérgicos/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sulfonamidas/farmacologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , Células PC12 , Inibidores de Proteínas Quinases/farmacologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Quinases Associadas a rho/antagonistas & inibidoresRESUMO
PURPOSE: The purpose of this study was to determine the relationships of communication dysfunction, body image, and amount of speaking in patients who were treated for head and neck cancers (HNCs). METHODS: This was a cross-sectional study of postoperative HNC patients at the otolaryngology outpatient departments of two leading medical centers in northern Taiwan. Data were collected using questionnaires to assess perceived communication dysfunction, body image, symptom severity, and amount of speaking after treatment. RESULTS: A total of 130 HNC patients were included in the analysis, and 70.8 % of patients reported speaking less after surgery as compared to the period before having HNC surgery. Overall, patients perceived a moderate level of communication dysfunction. Those with higher distress over their body image, higher symptom severity, and with hypopharyngeal and laryngeal cancer reported speaking less. Patients with advanced stage cancer and a tumor in a facial area and those that received reconstructive surgery were more likely to have a negative body image. CONCLUSIONS: Dissatisfaction with body image, greater symptom severity, and hypopharyngeal and laryngeal cancer are predictive of the amount HNC patients speak, as compared with the amount they spoke before having HNC. Clinicians should be aware of and systematically assess communication problems of HNC patients to promote their social function. Further research on interventions that facilitate the development of a positive body image and communication is strongly suggested.