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Renal cell carcinoma (RCC) is the most common kidney cancer with high mortality rate. Pazopanib has been approved for the treatment of RCC. However, the underlying mechanism is not clear. Here, we report a novel finding by showing that treatment with Pazopanib could promote cellular senescence of the human RCC cell line ACHN. Cells were stimulated with 5, 10, and 20 µM Pazopanib, respectively. Cellular senescence was measured using senescence-associated ß-galactosidase (SA-ß-Gal) staining. Western blot analysis and real-time polymerase chain reaction were used to measure the mRNA and protein expression of nuclear factor E2-related factor 2 (Nrf2), γH2AX, human telomerase reverse transcriptase (hTERT), telomeric repeat binding factor 2 (TERF2), p53 and plasminogen activator inhibitor (PAI). First, we found that exposure to Pazopanib reduced the cell viability of ACHN cells. Additionally, Pazopanib induced oxidative stress by increasing the production of reactive oxygen species, reducing the levels of glutathione peroxidase, and promoting nuclear translocation of Nrf2. Interestingly, Pazopanib exposure resulted in DNA damage by increasing the expression of γH2AX. Importantly, Pazopanib increased cellular senescence and reduced telomerase activity. Pazopanib also reduced the gene expression of hTERT but increased the gene expression of TERF2. Correspondingly, we found that Pazopanib increased the expression of p53 and PAI at both the mRNA and protein levels. To elucidate the underlying mechanism, the expression of Nrf2 was knocked down by transduction with Ad- Nrf2 shRNA. Results indicate that silencing of Nrf2 in ACHN cells abolished the effects of Pazopanib in stimulating cellular senescence and reducing telomerase activity. Consistently, knockdown of Nrf2 restored the expression of p53 and PAI in ACHN cells. Based on these results, we explored a novel mechanism whereby which Pazopanib displays a cytotoxicity effect in RCC cells through promoting cellular senescence mediated by Nrf2.
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Carcinoma de Células Renales , Indazoles , Neoplasias Renales , Pirimidinas , Sulfonamidas , Telomerasa , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Factor 2 Relacionado con NF-E2 , Telomerasa/genética , Proteína p53 Supresora de Tumor/genética , Neoplasias Renales/tratamiento farmacológico , ARN MensajeroRESUMEN
The effective discrimination and determination of the chiral antimalarial drugs quinine (QN) and quinidine (QD) are extremely important for human health. Herein, a 2D achiral Sm-based metal-organic framework (IMU-MOF1 = [Sm(tpba)(L)]n, where Htpba = 4-(2,2':6â³,2'-terpyridin)-4'-ylbenzioc acid and H2L = 2,2'-biquinoline-4,4'-dicarboxylic acid) was successfully prepared by the solvothermal method. More importantly, IMU-MOF1 was designed as an ultrasensitive fluorescent probe for the identification of chiral enantiomer drugs. The limits of detection for QN and QD are 4.24 × 10-11 and 7.54 × 10-12 M, respectively. Furthermore, it was demonstrated that the stronger hydrogen-bonding interactions between IMU-MOF1 and quinine furnish a more efficient energy transfer to the ligands in the sensing process, resulting in a significant fluorescence enhancement of IMU-MOF1.
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A transition metal coordination polymer, [Zn(tpba)(bqdbc)0.5]n (1), was successfully designed and synthesized based on 2,2'-biquinoline-4,4'-dicarboxylic acid (H2bqdc) and 4-(2,2';6',2'-terpyridin)-4'-yl)benzoic acid (Htpba). Compound 1 is initially constructed from the 1D chain of tpba- and bqdc2- and further connected by πâ¯π interactions, forming a 2D layered structure. Notably, compound 1 showed good fluorescence stability ranging from pH 1 to 13 in an aqueous solution. It was found that compound 1 could not only detect V2O74- ions with high selectivity and recyclability but also serve as an excellent selective sensing material for Fe3+ among some cations. More crucially, it is the first time that a luminescent coordination polymer has been used to detect V2O74- ions in aqueous solution. The detection of nitrotoluene (p-NT) demonstrated that compound 1 could also behave as a functional probe with high selectivity, sensitivity, and recyclability; and the detection limit of p-NT was 50.9 nM. Meanwhile, the luminescence sensing mechanisms for different analytes were speculated in detail.
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PURPOSE: The high recurrence rate after traditional transurethral resection of bladder tumor (TURBT) remains a challenge for management of non-muscle invasive bladder tumor (NMIBC). The aim of this study was to evaluate feasibility, efficacy and safety of surrounding en bloc resection using a general wire bipolar loop electrode and simultaneous intravesical chemotherapy. METHODS: We retrospectively analyzed data of 111 consecutive patients with NMIBC treated from June 2018 to December 2021. These patients underwent conventional TURBT and immediate intravesical chemotherapy (n = 45) or surrounding en bloc TURBT and simultaneous intravesical chemotherapy in the Urology Department of Harbin Medical University Cancer Hospital, The former and latter were defined as the conventional TURBT group and the surrounding en bloc TURBT group, respectively. All patients were followed up from 6 to 40 months, with an average of 24 months. Demographic characteristics, location and number of tumors, perioperative and postoperative data, pathological results and recurrence were documented. RESULTS: There were no significant differences in clinicopathological data between the conventional TURBT group (n = 45) and the surrounding en bloc TURBT group (n = 66). Operative time and complications associated with TURBT were comparable in the two groups. Recurrent tumors were found during follow-up in 2 (3.0%) of 66 patients in the surrounding en bloc group and 9 (20%) of 45 patients in the conventional group (p < 0.05). Lower urinary tract symptoms developed in 2 (3.0%) of 66 patients after surrounding en bloc TURBT and in 11(24.4%) of 45 patients after conventional TURBT (p < 0.05). CONCLUSION: Surrounding en bloc TURBT and simultaneous intravesical chemotherapy might significantly decrease the recurrence rate of NMIBC, and showed favorable safety and tolerability profiles. The general bipolar loop electrode was appropriate to complete the procedure.
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Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Estudios Retrospectivos , Cistectomía , Administración Intravesical , Tempo OperativoRESUMEN
BACKGROUND: This study aimed to evaluate bone response to micro-arc oxidation coated titanium alloy implants containing Ag. METHODS: 144 titanium alloy implants were prepared by machine grinding and divided into three treatment groups as following, SLA group: sand-blasting and acid-etched coating; MAO group: micro-arc oxidation without Ag coating; MAO + Ag group: micro-arc oxidation containing Ag coating. Surface characterization of three kind of implants were observed by X-ray diffraction, energy dispersive X-ray spectrometer, scanning electron microscopy, High Resolution Transmission Electron Microscope and roughness analysis. The implants were inserted into dog femurs. 4, 8 and 12 weeks after operation, the bone response to the implant to the bone was evaluated by push-out experiment, histological and fluorescent labeling analysis. RESULTS: MAO + Ag group consisted of a mixture of anatase and rutile. Ag was found in the form of Ag2O on the surface. The surface morphology of MAO + Ag group seemed more like a circular crater with upheaved edges and holes than the other two groups. The surface roughness of MAO and MAO + Ag groups were higher than SLA group, but no statistical difference between MAO and MAO + Ag groups. The contact angles in MAO + Ag group was smallest and the surface free energy was the highest among three groups. The maximum push-out strength of MAO and MAO + Ag groups were higher than SLA group at all time point, the value of MAO + Ag group was higher than MAO group at 4 and 8 weeks. Scanning electron microscopy examination for the surface and cross-section of the bone segments and fluorescent labeling analysis showed that the ability of bone formation and osseointegration in MAO + Ag group was higher than that of the other two groups. CONCLUSION: The micro-arc oxidation combination with Ag coating is an excellent surface modification technique to posse porous surface structure and hydrophilicity on the titanium alloy implants surface and exhibits desirable ability of osseointegration.
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Implantes Dentales , Oseointegración , Animales , Perros , Titanio/química , Aleaciones , Materiales Biocompatibles Revestidos/química , Propiedades de Superficie , Microscopía Electrónica de Rastreo , Oxidación-ReducciónRESUMEN
BACKGROUND: Cell autophagy has been proposed to be involved in drug resistance therapy. However, how the long non-coding RNA (lncRNA) reduces risks of drug resistance in renal cancer (RC) cells needs a thorough inquiry. This study was assigned to probe the effect and mechanism of HOTAIR on sunitinib resistance of RC. METHODS: Clinical RC tissues and para-carcinoma tissues were obtained to detect the expressions of miR-17-5p, HOTAIR and Beclin1. Sunitinib-resistant cells (786-O-R and ACHN-R) were constructed using parental RC cells (786-O and ACHN). The resistance of 786-O-R and ACHN-R cells to sunitinib was examined. Western blot and qRT-PCR were assayed to obtain the expressions of miR-17-5p, HOTAIR and Beclin1. The effects of HOTAIR knockdown or miR-17-5p overexpression/knockdown on cell autophagy and sunitinib resistance were measured by MDC staining, immunofluorescence and Western blot. The sensitivity of RC cells to sunitinib and change in cell clone formation after sunitinib treatment were assessed by CCK-8 assay and colony formation assay, respectively. The relationships among HOTAIR, miR-17-5p and Beclin1 were verified by dual-luciferase reporter gene and RIP assay. The role of HOTAIR knockdown in sunitinib resistance was verified in nude mice. RESULTS: HOTAIR expression in sunitinib-resistant cells is higher than that in parental cells. Knockdown of HOTAIR in sunitinib-resistant cells lead to refrained sunitinib resistance and cell autophagy both in vivo and in vitro. Activation of autophagy could raise resistance to sunitinib in RC cells, while inhibition of autophagy could improve the sensitivity of sunitinib-resistant cells to sunitinib. HOTAIR could compete with miR-17-5p to regulate Beclin1 expression. Knockdown of miR-17-5p in parental cells increases cell resistant to sunitinib, and overexpression of miR-17-5p in sunitinib-resistant cells increases cell sensitive to sunitinib. CONCLUSION: HOTAIR negatively targets miR-17-5p to activate Beclin1-mediated cell autophagy, thereby enhancing sunitinib resistance in RC cells.
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The isolation and modification of natural products is always a very important resources to anti-tumor drugs. Therefore, a novel series of tetrandrine and fangchinoline derivatives were designed and synthesized, and their antiproliferative activities against HepG2, MCF-7 cells were evaluated and described. From the activity result obtained, high to very high activity in vitro has been found, one of the tested compounds (compound 5d) exhibited the most significant cytotoxic effects. Compound 5d increased 29.2, 7.37 times anti-proliferative activity for HepG2 cells and MCF-7 cells compared to sunitinib (IC50=16.06µM and 25.41µM). Finally flow cytometry determined that compound 5d could indeed inhibit the proliferation of HepG2 cells via inducing apoptosis.
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Antineoplásicos/farmacología , Bencilisoquinolinas/farmacología , Diseño de Fármacos , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Bencilisoquinolinas/síntesis química , Bencilisoquinolinas/química , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Células MCF-7 , Estructura Molecular , Relación Estructura-ActividadRESUMEN
A transition metal coordination polymer (CP), [Cd(Hdpcp)]n (Cd-CP) was prepared based on 3-(2,4-dicarboxyphenyl)-6-carboxypyridine ligand (H3dpcp), and then its composite Eu@Cd-CP was synthesized by the post-modification through loading Eu3+ ions on Cd-CP. Eu@Cd-CP has outstanding fluorescence stability in aqueous solution with a wide range of pH. Furthermore, Eu@Cd-CP can distinguish sodium salicylate (SS) and sodium dehydroacetate (SA) in some food additives by quenching the characteristic fluorescence of Eu3+ ion. Eu@Cd-CP is the first known CP-based fluorescent probe for selective detection of SS and SA. In addition, the fluorescence mechanisms of discerning above analytes by Eu@Cd-CP have been thoroughly evaluated. It has found that synergistic effect of the dynamic process, photoinduced electron transfer (PET) process, energy absorption competition, and formation of Eu-O bonding interactions in sensing SA lead to the fluorescence quenching of Eu@Cd-CP. The fluorescence response mechanism of Eu@Cd-CP with SA is ascribed to the combination of the dynamic process, PET process, and energy absorption competition. A series of portable devices based on Eu@Cd-CP including fluorescence test strips, lamp beads, and composite films were developed to discern SS and SA via visual changes in luminescence color. This composite material can be potentially used as a multifunctional fluorescent probe for practical applications.
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Europio , Colorantes Fluorescentes , Aditivos Alimentarios , Espectrometría de Fluorescencia , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Europio/química , Aditivos Alimentarios/análisis , Polímeros/química , Concentración de Iones de HidrógenoRESUMEN
Curcumin, a polyphenol extracted from turmeric, is a potential alternative for the treatment of oral squamous cell carcinoma (OSCC) due to its remarkable anticancer activity and low systemic toxicity. To further enhance the anticancer activity and bioavailability of curcumin, we synthesized a curcumin analogue, AC17, by modifying the benzene ring and methylene group of curcumin. A soluble hyaluronic acid microneedle patch (AC17@HAMN) was developed to ensure accurate and safe delivery of AC17 to tumor tissues. The inhibitory effect of AC17 on OSCC cells was stronger than that of curcumin and some common analogues. Transcriptome sequencing showed that the target genes of AC17 were mainly concentrated in apoptosis, cell cycle and cell senescence pathways. Among them, AC17 induces cell cycle arrest and inhibits cell proliferation mainly by activating FOXO3 signaling. With good penetration and dissolution properties, microneedles can deliver AC17 directly to the tumor site and show good anti-tumor effect. Moreover, AC17@HAMN showed good biosafety. In summary, AC17@HAMN offers high efficiency, minimal invasiveness, and few adverse reactions. This microneedle patch holds great promise for potential clinical applications, especially for the treatment of OSCC.
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Carcinoma de Células Escamosas , Curcumina , Sistemas de Liberación de Medicamentos , Proteína Forkhead Box O3 , Neoplasias de la Boca , Agujas , Curcumina/administración & dosificación , Curcumina/farmacología , Curcumina/farmacocinética , Curcumina/química , Neoplasias de la Boca/tratamiento farmacológico , Humanos , Animales , Proteína Forkhead Box O3/metabolismo , Línea Celular Tumoral , Carcinoma de Células Escamosas/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Antineoplásicos/farmacocinética , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Ratones Endogámicos BALB C , Ratones , Ratones Desnudos , MasculinoRESUMEN
A d-f heterometallic MOF using the 2,2'-bipyridine-4,4'-dicarboxylic acid ligand (H2LZ) was obtained by solvothermal synthesis, namely [EuZn(LZ)2(HCOO)(H2O)3]n (1). The structure analysis shows that compound 1 comprises heterometallic Zn2+ and Eu3+ ions, which are connected by LZ2- and HCOO- anions to form a three-dimensional framework. MOF 1 exhibited high stability of fluorescence intensity in the scope of pH 2-11 in an aqueous solution. Furthermore, MOF 1 served as an excellent selective sensing material for the detection of folic acid in the presence of some imitating materials of the human body and discerned sulfaquinoxaline in sulfonamide drugs with high sensitivity, selectivity, and reusability. Moreover, we designed and manufactured a sensor paper based on MOF 1 as a portable device for the visual detection of folic acid and sulfaquinoxaline. More crucially, this is the first example in which luminescent MOF is used to identify sulfaquinoxaline molecules in an aqueous solution. In addition, the luminescence sensing mechanisms of MOF 1 for the detection of the above analytes were explored in detail.
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Ácido Fólico , Sulfaquinoxalina , Humanos , Luminiscencia , Agua , ZincRESUMEN
Translation and paraphrasing, as typical forms in second language (L2) communication, have been considered effective learning methods in second language acquisition (SLA). While many studies have investigated their similarities and differences in a process-oriented approach, little attention has been paid to the correlation in product quality between them, probably due to difficulties in assessing the quality of translation and paraphrasing. Current quality evaluation methods tend to be either subjective and one-sided or lack consistency and standardization. To address these limitations, we proposed preliminary evaluation frameworks for translation and paraphrasing by incorporating indices from natural language processing (NLP) tools into teachers' rating rubrics and further compared the product quality of the two activities. Twenty-nine translators were recruited to perform a translation task (translating from Chinese to English) and a paraphrasing task (paraphrasing in English). Their output products were recorded by key-logging technique and graded by three professional translation teachers by using a 10-point Likert Scale. This rating process adopted rubrics consisting of both holistic and analytical assessments. Besides, indices containing textual features from lexical and syntactic levels were extracted from TAASSC and TAALES. We identified indices that effectively predicted product quality using Pearson's correlation analysis and combined them with expert evaluation rubrics to establish NLP-assisted evaluation frameworks for translation and paraphrasing. With the help of these frameworks, we found a closely related performance between the two tasks, evidenced by several shared predictive indices in lexical sophistication and strong positive correlations between translated and paraphrased text quality according to all the rating metrics. These similarities suggest a shared language competence and mental strategies in different types of translation activities and perhaps in other forms of language tasks. Meanwhile, we also observed differences in the most salient textual features between translations and paraphrases, mainly due to the different processing costs required by the two tasks. These findings enrich our understanding of the shared ground and divergences in product quality between translation and paraphrasing and shed light on the pedagogical application of translation activities in classroom teaching. Moreover, the proposed evaluation framework can also bring insights into the development of standardized evaluation frameworks in translation and paraphrasing in the future.
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Intralingual translation has long been peripheral to empirical studies of translation. Considering its many similarities with interlingual translation, also described as translation proper, we adopted eye-tracking technology to investigate the cognitive process during translation and paraphrase, an exemplification of intralingual translation. Twenty-four postgraduate students were required to perform four types of tasks (Chinese paraphrase, English-Chinese translation, English paraphrase, Chinese-English translation) for source texts (ST) of different genres. Their eye movements were recorded for analysis of the cognitive effort and attention distribution pattern. The result demonstrated that: (1) Translation elicited significantly greater cognitive efforts than paraphrase; (2) Differences between translation and paraphrase on cognitive effort were modulated by text genre and target language; (3) Translation and paraphrase did not differ strikingly in terms of attention distribution. This process-oriented study confirmed higher cognitive efforts in inter-lingual translation, which was likely due to the additional complexity of bilingual transfer. Moreover, it revealed significant modulating effects of text genre and target language.
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Movimientos Oculares , Lenguaje , Cognición , Humanos , TraduccionesRESUMEN
Background: We aimed to explore miR-148a exerts a tumor suppressor effect and arsenic trioxide (As2O3) sensitivity on renal cell carcinoma (RCC). Methods: We performed polymerase chain reaction (PCR) on 42 pairs of tumor and paracancerous samples collected from RCC patients to investigate the miR-148a expression; meanwhile, we analyzed the interplay between clinical indicators and miR-148a expression of RCC. Then, the influence of miR-148a overexpression on the functions of RCC cells were analyze using transwell migration assay, Cell Counting Kit-8 (CCK-8), and cell wound healing assay. Furthermore, the ability of miR-148a to sensitize Caki-1 cells treated with As2O3 were detected using flow cytometry. Finally, the relevant mechanism of miR-148a on the downstream gene Wnt family member 10A (WNT10a) was explored by cell reverse method. Results: The results from RCC patients indicated a significantly lower miR-148a level than adjacent tissues. The low miR-148a expression increased prevalence of distant metastasis and decreased survival rate compared to those with high expression in patients. In the RCC cell lines, the proliferation and metastasis ability of the miR-148a mimic group was remarkably lower than the miR-NC group. At the same time, it was verified that WNT10a was remarkably higher cell lines and RCC tissues; and negatively related to miR-148a expression. In addition, miR-148a mimics were found to remarkably reduce the protein expression of WNT10a. In the cell reverse experiment, overexpression of WNT10a was confirmed to offset the miR-148a mimics effect on metastasis and proliferation of RCC cells. In addition, an increase in relative apoptosis was detected in As2O3 treated with/without miR-148a mimics for 48 hours, and apoptosis was significantly reduced after transfection with WNT10a in the Caki-1 cell line and significantly reduced after combined treatment. Conclusions: The study revealed that miR-148a is associated with distant metastases and leads to poor prognosis in RCC patients. Moreover, miR-148a inhibit the malignant progression and increase the sensitivity of RCC cells to As2O3 by regulating WNT10a.
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PURPOSE: Bladder cancer is a common malignant tumor of the urinary system, with the fourth-highest incidence of male malignant tumors in Europe and the United States. So far, the mechanism of bladder cancer progression and metastasis has not been clarified. The aim of our study was to validate the way of long noncoding RNA (lncRNA) KCNMB2-AS1 on the metabolism and growth of bladder cancer cells by miR-3194-3p/SMAD5. PATIENTS AND METHODS: The Gene Expression was analyzed by qRT-PCR in bladder cancer tissues and cell lines, with the highly expressed KCNMB2-AS1 screened out. Cell proliferation was detected by Edu staining and clone formation assay, cell migration, and invasion by wound healing and transwell assays. Cell stemness was determined by assessing sphere-forming ability and stemness marker. Correlation between miRNA and lncRNA/gene was verified by dual-luciferase assay and RIP, and the effect of KCNMB2-AS1 on bladder cancer growth by nude mice tumor formation experiment. RESULTS: Here, we revealed the increased level of KCNMB2-AS1 in bladder cancer for the first time. Knockdown of KCNMB2-AS1 in vitro prevented the ability of proliferation, metastasis, and stemness of cancer cells. In vivo, the silencing of KCNMB2-AS1 also prevented tumor growth in vivo. Next, we revealed that KCNMB2-AS1 could interact with miR-3194-3p and uncovered that SAMD5 was a downstream target of miR-3194-3p. CONCLUSION: In conclusion, KCNMB2-AS1 mediated the bladder cancer cells progress by regulating the miR-3194-3p/SAMD5 signal pathway, which would provide a new target for bladder cancer research.
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Although simultaneous interpreting (SI) is generally recognized as a highly demanding cognitive activity in nature, the role of cognitive processes in SI fluency is yet to be determined. While utterance fluency refers to the set of objectively determined oral features of utterances, cognitive fluency means the speaker's efficient mobilization and integration of underlying cognitive processes responsible for utterance production. An investigation into the relationship of the two dimensions of fluency helps to reveal the cognitive bases of interpreting. This study explores the predicting power of cognitive fluency in the utterance fluency development of L2 (English)-L1 (Chinese) SI output of trainee interpreters. Cognitive fluency was operationalized as measures of lexical access, linguistic attention control, and working memory capacity. Measures of utterance fluency were obtained through simulated SI tasks under conditions of low and high input rates. Twenty-eight trainees interpreted two speeches, one with a high input rate and the other with a low input rate, at the beginning and end of an SI training period of 13 weeks. A bilingual corpus of the participants' SI output was built, and indicators of SI utterance fluency were annotated systematically. Utterance fluency was indexed by the speech rate, mean length of run, phonation time ratio, mean number of silent pauses, and mean number of disfluencies. Results of analyses indicated that (1) the predicting power of cognitive fluency for SI utterance fluency development was only shown under high cognitive load over a training period of 13 weeks; (2) predictors for the development of SI utterance fluency tended to be the efficiency of cognitive processes involved in the target language production stage; and (3) the inclusion of measures of working memory capacity significantly increased the predicting power of cognitive fluency for SI utterance fluency development. This study for the first time provides evidence for the role of cognitive fluency in trainee interpreters' SI utterance fluency development, having implications for the theoretical framework of cognitive fluency and the information processing mechanism in interpreting process, as well as for interpreter aptitude tests and interpreting pedagogy.
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The por1 gene encoding one of the mitochondrial porin channels in C. utilis CCTCC M 209298 was disrupted using a homologous recombination method. The co-production of S-adenosylmethionine (SAM) and glutathione (GSH) in the mutant C. utilis Δpor1 increased by 34.9% and 25.1%, respectively, during batch and fed-batch fermentation, relative to the parental strain. The average oxygen consumption rate, activities of key enzymes involved in SAM and GSH biosynthesis, levels of intracellular cofactors such as NADH and ATP, and carbon fluxes of key metabolites were compared between the parental strain and the Δpor1 mutant. The disruption of por1 gene increased the rate of mitochondrial respiration, increased the activities of both methionine adenosyltransferase and γ-glutamylcysteine synthetase, and enhanced the supply of energy and substrates for SAM and GSH biosynthesis, all of which favored the overproduction of SAM and GSH in the Δpor1 mutant.
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Candida/genética , Proteínas Fúngicas/genética , Glutatión/metabolismo , Ingeniería Metabólica/métodos , Porinas/genética , S-Adenosilmetionina/metabolismo , Proteínas Fúngicas/metabolismo , Edición Génica/métodos , Glutatión/análisis , Recombinación Homóloga , Porinas/metabolismo , S-Adenosilmetionina/análisisRESUMEN
Clear cell renal cell carcinoma (ccRCC) is a common malignant kidney tumor, the pathogenesis of which remains unclear. The aim of the present study was to investigate whether caspase-10, matrix metalloproteinase-9 (MMP-9) and total laminin (LM) were involved into the pathogenesis of ccRCC. The levels of caspase-10, MMP-9 and total LM were analyzed by ELISA in tumor tissues and adjacent non-malignant tissues of 27 patients with ccRCC. The results revealed that caspase-10 levels in the tumor tissues were significantly higher than those in the adjacent non-malignant tissues (P<0.05). The MMP-9 levels in the tumor tissues were significantly lower than those in adjacent non-malignant tissues (P<0.01). The total LM levels in tumor tissues revealed no statistical difference with those in the adjacent non-malignant tissues (P=0.757). Additionally, caspase-10 levels were positively correlated with MMP-9 levels (P<0.001), but negatively correlated with total LM levels (P<0.05) in tumor tissues. Correlation analyses with clinical data of patients with ccRCC, revealed that caspase-10 levels (P<0.05) and MMP-9 levels (P<0.001) in tumor tissues were positively correlated with tumor grades of ccRCC, whereas total LM levels were positively correlated with tumor size (P<0.05). The results of the present study suggested that interactions between caspase-10, MMP-9 and LM are likely involved in the pathogenesis of ccRCC. A deeper understanding of the correlation between caspase-10, MMP-9 and LM would aid the clarification of pathogenesis of ccRCC.
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Majorana stars are visual representation for a quantum pure state. For some states, the corresponding majorana stars are located on one curve on the Block sphere. However, it is lack of exact curve equations for them. To find the exact equations, we consider a superposition of two bosonic coherent states with an arbitrary relative phase. We analytically give the curve equation and find that the curve always goes through the North pole on the Block sphere. Furthermore, for the superpositions of SU(1,1) coherent states, we find the same curve equation.
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Dental pulp/dentine complex regeneration is indispensable to the construction of biotissue-engineered tooth roots and represents a promising approach to therapy for irreversible pulpitis. We used a tissue-engineering method based on odontogenic stem cells to design a three-dimensional (3D) and scaffold-free stem-cell sheet-derived pellet (CSDP) with the necessary physical and biological properties. Stem cells were isolated and identified and stem cells from root apical papilla (SCAPs)-based CSDPs were then fabricated and examined. Compact cell aggregates containing a high proportion of extracellular matrix (ECM) components were observed, and the CSDP culture time was prolonged. The expression of alkaline phosphatase (ALP), dentine sialoprotein (DSPP), bone sialoprotein (BSP) and runt-related gene 2 (RUNX2) mRNA was higher in CSDPs than in cell sheets (CSs), indicating that CSDPs have greater odonto/osteogenic potential. To further investigate this hypothesis, CSDPs and CSs were inserted into human treated dentine matrix fragments (hTDMFs) and transplanted into the subcutaneous space in the backs of immunodeficient mice, where they were cultured in vivo for 6 weeks. The root space with CSDPs was filled entirely with a dental pulp-like tissue with well-established vascularity, and a continuous layer of dentine-like tissue was deposited onto the existing dentine. A layer of odontoblast-like cells was found to express DSPP, ALP and BSP, and human mitochondria lined the surface of the newly formed dentine-like tissue. These results clearly indicate that SCAP-CSDPs with a mount of endogenous ECM have a strong capacity to form a heterotopic dental pulp/dentine complex in empty root canals; this method can be used in the fabrication of bioengineered dental roots and also provides an alternative treatment approach for pulp disease.