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Beauveria bassiana is a popular and eco-friendly biopesticide. During its pathogen-pest interaction, both N-acetylglucosamine (GlcNAc) catabolism and anabolism are crucial for nutrient supply and cell-wall construction. The initiation of GlcNAc metabolism relies on the catalysis of GlcNAc kinase, which has been extensively studied in the human pathogen Candida albicans. However, the physiological function of GlcNAc kinase remains poorly understood in entomopathogenic fungi. In the present study, a GlcNAc kinase homolog was identified and designated as BbHxk1 in B. bassiana. Deletion of BbHxk1 resulted in viable but reduced vegetative growth on various carbon sources. ΔBbHxk1 mutants displayed severe defects in cell wall integrity, making them more susceptible to cell wall stress cues. Furthermore, the absence of BbHxk1 resulted in an increase in conidial yield and blastospore production, and a faster rate of germination and filamentation, potentially attributed to higher intracellular ATP levels. BbHxk1 deficiency led to a reduction in the activities of cuticle-degrading enzymes, which might contribute to the attenuated pathogenicity specifically through cuticle penetration rather than hemocoel infection towards Galleria mellonella larvae. Being different from C. albicans Hxk1, which facultatively acts as a catalyzing enzyme and transcriptional regulator, BbHxk1 primarily acts as a catalyzing enzyme and metabolic regulator. The altered metabolomic profiling correlated with the phenotypic defects in ΔBbHxk1 mutants, further implicating a potential metabolism-dependent mechanism of BbHxk1 in mediating physiologies of B. bassiana. These findings not only unveil a novel role for GlcNAc kinase in B. bassiana, but also provide a solid theoretical basis to guide metabolic reprogramming in order to maintain or even enhance the efficiency of fungi for practical applications.
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Beauveria , Pared Celular , Fosfotransferasas (Aceptor de Grupo Alcohol) , Beauveria/patogenicidad , Beauveria/genética , Pared Celular/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Animales , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Esporas Fúngicas , Mariposas Nocturnas/microbiología , Agentes de Control BiológicoRESUMEN
High-quality evidence indicated that both neoadjuvant carboplatin/paclitaxel (CROSS) and cisplatin/5-fluorouracil (PF) regimens in combination with radiotherapy improve survival outcomes compared to surgery alone in patients with esophageal cancer. It is not yet known whether they may differ in terms of treatment burden and healthcare costs. A total of 232 Taiwanese patients with esophageal squamous cell carcinoma who had undergone neoadjuvant chemoradiotherapy (nCRT) with either the CROSS (n = 153) or the PF (n = 79) regimens were included. Hospital encounters and adverse events were assessed for determining treatment burden. Cost-effectiveness analysis was undertaken using the total costs incurred over 3 years in relation to overall survival (OS) and progression-free survival (PFS). Compared with PF, the CROSS regimen was associated with a lower treatment burden: shorter inpatient days on average (4.65 ± 10.05 vs. 15.14 ± 17.63 days; P < 0.001) and fewer admission requirements (70% of the patients were never admitted vs. 20% in the PF group; P < 0.001). Patients in the CROSS group experienced significantly less nausea, vomiting, and diarrhea. While the benefits observed in the CROSS group were associated with additional nCRT-related expenditures (1388 United States dollars [USD] of added cost per patient), this regimen remained cost-effective. At a willingness-to-pay threshold of 50,000 USD per life-year, the probability of the CROSS regimen to be more cost-effective than PF was 94.1% for PFS but decreased to 68.9% for OS. The use of the CROSS regimen for nCRT in patients with ESCC was associated with a lower treatment burden and was more cost-effective than PF.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/terapia , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Terapia Neoadyuvante , Análisis de Costo-Efectividad , Estudios Retrospectivos , Fluorouracilo , Cisplatino , Paclitaxel , Quimioradioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Objective To summarize the research findings on the measurement properties and value set of EuroQol Five-Dimensional Questionnaire-Youth Version (EQ-5D-Y). Methods PubMed,Web of Science,CNKI,and Wanfang Data were searched for the studies involving the measurement properties and value set of EQ-5D-Y. Results According to the inclusion and exclusion criteria,38 studies were included for analysis.EQ-5D-Y had good feasibility,reliability,and validity in measuring health-related quality of life (HRQOL) of youth in different countries and populations.The advantages of 5-level EQ-5D-Y (Y-5L)over 3-level EQ-5D-Y (Y-3L) might be modest.The available studies have demonstrated that the EQ-5D value set for adults should not be adopted in youth,and the international protocol for constructing the Y-3L value set has been available.Many countries have established or are developing their own Y-3L value sets according to the protocol. Conclusion The study systematically elaborated the current status and trend of the measurement properties and value set of EQ-5D-Y,which could provide reference for the future research on the EQ-5D-Y in China.
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Calidad de Vida , Adolescente , Adulto , China , Humanos , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, resulted from the silencing of the Fmr1 gene and the subsequent loss of fragile X mental retardation protein (FMRP). Spine dysgenesis and cognitive impairment have been extensively characterized in FXS; however, the underlying mechanism remains poorly understood. As an important regulator of spine maturation, intercellular adhesion molecule 5 (ICAM5) mRNA may be one of the targets of FMRP and involved in cognitive impairment in FXS. Here we show that in Fmr1 KO male mice, ICAM5 was excessively expressed during the late developmental stage, and its expression was negatively correlated with the expression of FMRP and positively related with the morphological abnormalities of dendritic spines. While in vitro reduction of ICAM5 normalized dendritic spine abnormalities in Fmr1 KO neurons, and in vivo knockdown of ICAM5 in the dentate gyrus rescued the impaired spatial and fear memory and anxiety-like behaviors in Fmr1 KO mice, through both granule cell and mossy cell with a relative rate of 1.32 ± 0.15. Furthermore, biochemical analyses showed direct binding of FMRP with ICAM5 mRNA, to the coding sequence of ICAM5 mRNA. Together, our study suggests that ICAM5 is one of the targets of FMRP and is implicated in the molecular pathogenesis of FXS. ICAM5 could be a therapeutic target for treating cognitive impairment in FXS.SIGNIFICANCE STATEMENT Fragile X syndrome (FXS) is characterized by dendritic spine dysgenesis and cognitive dysfunctions, while one of the FMRP latent targets, ICAM5, is well established for contributing both spine maturation and learning performance. In this study, we examined the potential link between ICAM5 mRNA and FMRP in FXS, and further investigated the molecular details and pathological consequences of ICAM5 overexpression. Our results indicate a critical role of ICAM5 in spine maturation and cognitive impairment in FXS and suggest that ICAM5 is a potential molecular target for the development of medication against FXS.
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Disfunción Cognitiva/metabolismo , Espinas Dendríticas/metabolismo , Síndrome del Cromosoma X Frágil/metabolismo , Regulación de la Expresión Génica/fisiología , Glicoproteínas de Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Animales , Disfunción Cognitiva/genética , Espinas Dendríticas/patología , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Síndrome del Cromosoma X Frágil/complicaciones , Síndrome del Cromosoma X Frágil/genética , Masculino , Ratones , Ratones Noqueados , Neurogénesis/genéticaRESUMEN
OBJECTIVE: To explore the effects of low-dose dexmedetomidine (DM) combined with hydromorphone (HM) in postoperative analgesia and on levels of serum interleukin-6 (IL-6) and C-reactive protein (CRP) in PCa patients. METHODS: Using the random number table, we divided 102 PCa patients undergoing radical prostatectomy from January 2019 to November 2020 into a trial group (n = 51) and a control group (n = 51), the former given HM and the latter low-dose DM + HM for postoperative analgesia. We recorded the postoperative resuscitation time, extubation time and pain, perioperative cognitive function, IL-6 and CRP levels, and drug-related adverse reactions of the patients, and compared them between the two groups. RESULTS: There was no statistically significant difference in postoperative resuscitation time and extubation time between the two groups of patients (P > 0.05). The frequency of patient-controlled epidural analgesia (PCEA) compressions was lower in the trial than in the control group within 24 hours after surgery (P < 0.05). The Visual Analogue Scale (VAS) scores were higher in both of the groups at 24 hours than at 4, 12, and 48 hours after surgery (P < 0.05), at 12 hours than at 4 and 48 hours (P < 0.05) and at 4 hours than at 48 hours (P < 0.05), but lower in the trial than in the control group at 4, 12 and 24 hours postoperatively (P < 0.05). No statistically significant difference was observed in the scores of the Mini Mental State Evaluation Scale between the two groups of patients (P > 0.05). The levels of IL-6 and CRP were higher in both of the groups at 24 hours after than before and at 4, 12 and 48 hours after surgery (P < 0.05), at 48 hours after than before and at 4 and 12 hours after surgery (P < 0.05), at 12 hours after than before and at 4 hours after surgery (P <0.05), and at 4 hours after than before surgery (P < 0.05), but lower in the trial than in the control group at 4, 12, 24 and 48 hours postoperatively (P < 0.05). There was no statistically significant difference in the total incidence rate of adverse reactions between the two groups (P > 0.05). CONCLUSIONS: Low-dose dexmedetomidine combined with hydromorphone is a safe and effective option for postoperative analgesia in PCa patients, and it can inhibit the expression of inflammatory factors.
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Analgesia , Dexmedetomidina , Neoplasias de la Próstata , Humanos , Hidromorfona , Interleucina-6 , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/cirugíaRESUMEN
The balance between stem cell self-renewal and differentiation is controlled by intrinsic factors and niche signals. In the Drosophila melanogaster ovary, some intrinsic factors promote germline stem cell (GSC) self-renewal, whereas others stimulate differentiation. However, it remains poorly understood how the balance between self-renewal and differentiation is controlled. Here we use D. melanogaster ovarian GSCs to demonstrate that the differentiation factor Bam controls the functional switch of the COP9 complex from self-renewal to differentiation via protein competition. The COP9 complex is composed of eight Csn subunits, Csn1-8, and removes Nedd8 modifications from target proteins. Genetic results indicated that the COP9 complex is required intrinsically for GSC self-renewal, whereas other Csn proteins, with the exception of Csn4, were also required for GSC progeny differentiation. Bam-mediated Csn4 sequestration from the COP9 complex via protein competition inactivated the self-renewing function of COP9 and allowed other Csn proteins to promote GSC differentiation. Therefore, this study reveals a protein-competition-based mechanism for controlling the balance between stem cell self-renewal and differentiation. Because numerous self-renewal factors are ubiquitously expressed throughout the stem cell lineage in various systems, protein competition may function as an important mechanism for controlling the self-renewal-to-differentiation switch.
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Unión Competitiva , Diferenciación Celular , Drosophila melanogaster/citología , Drosophila melanogaster/metabolismo , Complejos Multiproteicos/química , Complejos Multiproteicos/metabolismo , Péptido Hidrolasas/química , Péptido Hidrolasas/metabolismo , Células Madre/citología , Células Madre/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Animales , Complejo del Señalosoma COP9 , Proliferación Celular , ADN Helicasas/metabolismo , Proteínas de Drosophila/metabolismo , Femenino , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Proteína NEDD8 , Ovario/citología , Unión Proteica , Ubiquitinas/metabolismoRESUMEN
A less invasive endoscopic therapy has been used as a routine treatment for superficial esophageal squamous cell carcinoma (SESCC). However, lymph node metastasis (LNM) in SESCC limits the effectiveness of this medical procedure. This meta-analysis aimed to screen the risk factors for LNM in SESCC in Asia to provide evidence for clinicians in selecting treatment. We searched the main reference databases for research involving patients who received esophagectomy (open or minimally invasive) with lymph node dissection for SESCC. Meta-analysis was performed using RevMan 5.3 software. Twenty studies including 3983 patients were obtained in this analysis. The meta-analysis showed that tumor size, macroscopic type of tumor, degree of differentiation, depth of tumor invasion, and lymphovascular involvement are risk factors of LNM in SESCC, whereas age, sex, and tumor location showed no association with LNM. Five variables were screened as predictive factors for LNM in SESCC. The incidence of LNM in SESCC is not rare, and the physicians must be careful when making clinical decisions.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neoplasias de Cabeza y Cuello , Asia , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago/cirugía , Esofagectomía , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Metástasis Linfática , Invasividad Neoplásica , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Phthalate esters (PAEs) and organophosphate esters (OPEs) were identified and quantified in surface soils from farmland and riparian areas of the Three Gorges Reservoir (TGR), western China. Generally, the mean values of PAEs and OPEs were 618 and 266 ng/g dry weight (dw) in farmland soil and 560 and 499 ng/g dw in riparian soil, respectively. The occurrence of OPEs should be regarded as a risk factor in the TGR region. Analogous spatial distribution patterns for PAEs were observed with higher concentrations observed at site WZ in both types of soil, which might relate to the anthropogenic activities. The hydrodynamic conditions might be important factors contributing to the slightly different spatial distribution of OPEs. The concentrations of OPEs in riparian soil exceed those in farmland soil at all sampling sites, which could partly be ascribed to the complete operation of the TGR. Dibutyl phthalate (DnBP) was the most dominated PAEs congener in both types of soil. Of particular note is the elevated contribution of tris(methylphenyl) phosphate (TMPP), followed by 2-ethylhexyl diphenyl phosphate (EHDPP), accounting for more than 90% of the total OPEs, and the shipping or/and the local human activity might be considered as the major contributor. The slight differences in PAEs composition of principal components might largely attribute to the variety of emission sources in two types of soil. The different cluster patterns between two types of soil indicated that the anthropogenic activities as well as the full operation of TGR, may play a role.
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Ácidos Ftálicos/análisis , Contaminantes del Suelo/análisis , China , Dibutil Ftalato/análisis , Monitoreo del Ambiente/métodos , Ésteres/análisis , Organofosfatos/análisisRESUMEN
In the present study, the occurrence, concentrations, and distribution of organophosphate esters (OPEs) were studied in surface soil and street dust samples collected from different sites of Chongqing, a metropolitan city in western China. Furthermore, nondietary daily intakes (DIs) of OPEs only through dust ingestion absorption were assessed between toddlers and adults. The ∑OPEs contents ranged from 10.1 to 315 ng/g dw and from 348 to 1369 ng/g dw in surface soil and street dust samples, respectively, with tris (2-butoxyethyl) phosphate (TBOEP), the predominant OPEs in surface soil, whereas tris (chloroethyl) phosphate (TCEP) occupied a relatively high proportion in street dust samples. The mobility of TCEP and tris (2-chloroisopropyl) phosphate (TCIPP) to deeper soil zones with seepage water may play a role in decreasing contents of both compounds in surface soil. Considerably different patterns of pairwise correlations of six OPEs congeners were observed between surface soil and street dust, which could largely relate to the complicated environmental process for tris (1,3-dichloroisopropyl) phosphate (TDCIPP) and TCIPP in surface soil. Analogous sources between surface soil and street dust have been identified through principal component analysis. Compared with adults, the toddlers were more vulnerable to OPEs intake, according to the estimated DI values. For both toddler and adult groups, the estimated exposure values for all OPEs were several orders of magnitude lower than the reference dose (RfD), not suggesting the potential risk to human health.
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Exposición a Riesgos Ambientales/estadística & datos numéricos , Ésteres/análisis , Organofosfatos/análisis , Contaminantes del Suelo/análisis , China , Ciudades , Polvo/análisis , Monitoreo del Ambiente , Retardadores de Llama/análisis , Humanos , Suelo/químicaRESUMEN
Purpose: The present study aimed to investigate the clinical prognostic significance of radiomics signature (R-signature) in patients with gastric neuroendocrine neoplasm (GNEN). Methods and Materials: A retrospective study of 182 patients with GNEN who underwent dual-phase enhanced computed tomography (CT) scanning was conducted. LASSO-Cox regression analysis was used to screen the features and establish the arterial, venous and the arteriovenous phase combined R-signature, respectively. The association between the optimal R-signature with the best prognostic performance and overall survival (OS) was assessed in the training cohort and verified in the validation cohort. Univariate and multivariate Cox regression analysis were used to identify the significant factors of clinicopathological characteristics for OS. Furthermore, the performance of a combined radiomics-clinical nomogram integrating the R-signature and independent clinicopathological risk factors was evaluated. Results: The arteriovenous phase combined R-signature had the best performance in predicting OS, and its C-index value was better than the independent arterial and venous phase R-signature (0.803 vs 0.784 and 0.803 vs 0.756, P<0.001, respectively). The optimal R-signature was significantly associated with OS in the training cohort and validation cohort. GNEN patients could be successfully divided into high and low prognostic risk groups with radiomics score median. The combined radiomics-clinical nomogram combining this R-signature and independent clinicopathological risk factors (sex, age, treatment methods, T stage, N stage, M stage, tumor boundary, Ki67, CD56) exhibited significant prognostic superiority over clinical nomogram, R-signature alone, and traditional TNM staging system (C-index, 0.882 vs 0.861, 882 vs 0.803, and 0.882 vs 0.870 respectively, P<0.001). All calibration curves showed remarkable consistency between predicted and actual survival, and decision curve analysis verified the usefulness of the combined radiomics-clinical nomogram for clinical practice. Conclusions: The R-signature could be used to stratify patients with GNEN into high and low risk groups. Furthermore, the combined radiomics-clinical nomogram provided better predictive accuracy than other predictive models and might aid clinicians with therapeutic decision-making and patient counseling.
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BACKGROUND: This retrospective study examined outcomes in esophageal squamous cell carcinoma (ESCC) patients who did not undergo surgical resection after neoadjuvant chemoradiotherapy (nCRT). METHODS: Patients receiving nCRT between 2012 and 2020 were divided into two groups: group 1 (scheduled surgery) and group 2 (no surgery). Group 2 was further categorized into subgroups based on reasons for not proceeding to surgery: group 2a (disease progression), group 2b (poor general conditions), and group 2c (patient refusal). Overall survival (OS) was the primary outcome. RESULTS: Group 1 comprised 145 patients, while subgroups 2a, 2b, and 2c comprised 24, 16, and 31 patients, respectively. The 3-year OS rate was significantly lower in group 2 compared with group 1 (34% versus 56%, p < 0.001). A subgroup analysis showed varying 3-year OS rates: 13% for group 2a, 25% for group 2b, and 58% for group 2c (p < 0.001). Propensity score matching for group 2c and group 1 revealed no significant difference in 3-year OS rates (p = 0.91). CONCLUSION: One-third of ESCC patients receiving nCRT did not undergo surgical resection. Overall survival in this group was generally poorer, except for those who refused surgery (group 2c).
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OBJECTIVE: To identify the significant predictors of overall survival for patients living with diffused large B-cell lymphoma (DLBCL) in the central nervous system and establish a novel decision tree model to help predict survival status at several time points. METHODS: Patients diagnosed with DLBCL were identified from the SEER database and randomly divided into training and test samples (6:4). Dichotomous decision trees were developed for survival status at 3, 12, 24, and 60 months. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy rate, and area under the receiver operating characteristic curve were calculated to evaluate the model performance. RESULTS: A total of 2998 patients were included, with 1799 and 1199 patients divided into the training and testing groups. Decision trees for 3, 12, 24, and 60 months survival status were generated. Chemotherapy and patient's age were of the primary importance for prognosis in the novel models. Favorable consistency between the predicted and actual survival status was presented. The accuracy rates were 0.79, 0.71, 0.68, and 0.86 for training sample at 3, 12, 24, and 60 months, respectively, and 0.75, 0.69, 0.58, and 0.84 for test sample at 3, 12, 24, and 60 months, respectively. The area under the receiver operating characteristic curve values ranged between 0.645 and 0.721 for the training sample and between 0.607 and 0.712 for the test sample. CONCLUSIONS: Novel decision tree models were established for predicting the 3, 12, 24, and 60 months survival status of patients with DLBCL. The newly developed models were verified using training and test samples, showing favorable accuracy and predictive value on overall survival.
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Linfoma de Células B Grandes Difuso , Sistema Nervioso Central , Árboles de Decisión , Humanos , Linfoma de Células B Grandes Difuso/terapia , Pronóstico , Curva ROCRESUMEN
Extranodal nasal NK/Tcell lymphoma (ENKTCL) is a relatively rare type of non-Hodgkin's lymphoma. It is highly malignant, highly invasive, and easy to relapse. Most patients have a poor prognosis. We report a 48-year-old woman who presented with irritant dry cough that had persisted for 6 m. CT showed a mass in the right nasal cavity, with uneven density similar to soft tissue, with slight uneven enhancement. The mass and the upper, middle, and lower turbinates were not clearly demarcated, involving multiple adjacent sinus cavities, and the local bone showed osteolytic destruction; MRI showed isosignal on T1WI and slightly hypersignal on T2WI and DWI. In addition, there was a mass of soft tissue density at the bronchial opening in the right middle lobe, showing uneven and obvious enhancement; a cavity was seen in the nodule of the right lower lobe, and the adjacent pleura was stretched, showing moderate enhancement. The nasal mass was diagnosed as extranodal NK/T cell lymphoma, the right middle lobe mass was diagnosed as mucoepidermoid carcinoma, and the right lower lobe mass was diagnosed as lung adenocarcinoma. ENKTCL rarely invades the lungs. If a patient has a lung occupying lesion similar to it, biopsy confirmation should be considered to avoid misdiagnosis as a chest metastasis that affects the treatment effect.
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Pancreatoblastoma is a rare primary pancreatic neoplasm of children that may arise in any portion of the pancreas. We report a case of a 3-yr-old boy who presented to with abdominal pain our hospital and a progressive bulge in his right abdomen. Biochemical evaluation and serum levels of tumoral markers were within reference limits. On the computed tomography, two tumors were found. One located in the head of the pancreas; however, a laparotomy revealed that the head of pancreas was compressed but normal. The other was in the left abdomen near the spleen and the tail of the pancreas. The diagnosis of two synchronous pancreatoblastoma originating from the omentum was confirmed by pathology. Therefore, a pancreatoblastoma should be considered when a large well-defined, lobulated, and heterogeneous mass is identified in the pancreas of children. In addition, an ectopic pancreatoblastoma should be considered when identified within or near the ectopic pancreatic tissue.
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Neoplasias Pancreáticas/patología , Antineoplásicos/uso terapéutico , Preescolar , Quimioterapia Combinada , Humanos , Laparotomía , Masculino , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/cirugía , Tomografía Computarizada por Rayos XRESUMEN
In this study, the absorption behavior of five organophosphate esters (OPEs) congeners was monitored in a water-soil system, and three absorption isotherm equations were modeled. Furthermore, the factors influencing the absorption process including temperature and dissolved organic carbon (DOC) were also investigated. The results showed that an equilibrium state was reached after 12 hours of absorption for these five OPEs congeners, which could be appropriately modeled by the Freundlich isotherm equations with R2 values ranging from 0.963 to 0.995. Significant correlations were observed among the Kd (partitioning coefficient) values and similar chemical structures of OPEs. The Kd values decreased with increasing temperature, indicating the significant role played by temperature. TBEP and TDCP were highly impacted by the DOC content, and for the other OPEs congeners, no clear tendency in Kd values was found with increasing of DOC content.
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BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become important treatment options for non-small cell lung cancer (NSCLC) patients with EGFR sensitive mutation. However, the detection of EGFR driver mutation is impeded by the lack of adequate tumor tissues, histopathological type, long detection period, and the heterogeneity of a tumor. Therefore, it is necessary to develop a more convenient method to guide the clinical use of EGFR-TKI. Circular RNAs (circRNAs) are characterized as a closed structure with covalently joined ends resistant to exonucleases may be a potential biomarker. In the present study, we aimed to screen circRNAs that may be associated with the efficacy of EGFR-TKI. METHODS: The expression of circRNAs sequenced by circular microarray in plasma samples between gefitinib effective and ineffective groups were compared. RT-qPCR further validated the results in an independent cohort. Kaplan-Meier curves were used to analyze the association between circRNA and progression-free survival (PFS) of NSCLC patients treated with gefitinib. RESULTS: In total, 52 NSCLC patients treated with gefitinib were included for analysis. 1,377 circRNAs were differentially expressed in gefitinib effective and ineffective groups, among which 989 circRNAs were up-regulated, and 388 circRNAs were down-regulated in the effective group. Furthermore, two differentially expressed circRNAs, hsa_circ_0109320 and hsa_circ_0134501, were validated by RT-qPCR in an independent cohort of 38 gefitinib-treated NSCLC patients. Elevated hsa_circ_0109320 was associated with longer PFS in gefitinib-treated NSCLC patients. CONCLUSIONS: Taken together, hsa_circ_0109320 may be a potential biomarker for the efficacy of EGFR-TKI in NSCLC patients. This provides a new molecular typing method for individualized precision treatment.
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Glioma invasion is a main cause of a poor prognosis and relapse in patients suffering from the disease. However, the molecular mechanisms responsible for glioma cell invasion remain poorly understood. In this study, the characteristics of exosomes were identified using electron microscope (TEM), and western blot analysis. The potential mechanism of long noncoding RNA (lncRNA) activated by TGFß (lncRNAATB) was demonstrated using luciferase reporter assays and RNA immunoprecipitation. We found that glioma cellderived exosomes promoted the activation of astrocytes and had the ability to shuttle long noncoding RNA (lncRNA) activated by TGFß (lncRNAATB) to astrocytes. More importantly, lncRNAATB activated astrocytes through the suppression of microRNA (miRNA or miR)2043p in an Argonaute 2 (Ago2)dependent manner. Furthermore, astrocytes activated by lncRNAATB in turn promoted the migration and invasion of glioma cells. Taken together, the findings of this study suggest that lncRNAATB may play an important role in modulating glioma microenvironment through exosomes. Thus, a better understanding of this process may provide implications for the prevention of highly invasive glioma.
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Exosomas/genética , Glioma/genética , ARN Largo no Codificante/genética , Factor de Crecimiento Transformador beta/genética , Astrocitos/metabolismo , Astrocitos/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glioma/patología , Humanos , MicroARNs/genética , Microscopía Electrónica , Invasividad Neoplásica/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Microambiente Tumoral/genéticaRESUMEN
In this study, we investigated the effects of organophosphate ester (OPE) concentrations, temperature, soil organic matter, and microorganisms on the migration and release of several common OPEs from fluctuation zone soil in the Three Gorges Reservoir (TGR) to the overlying water by simulation experiments in the lab. The results indicate that the release of OPEs is determined based on their concentrations in the soil. The release of OPEs from soil to the overlying water decreases with increasing organic matter content, which indicates that the presence of organic matter could inhibit the migration of OPEs. However, the inhibition of the release of OPEs of organic matter is not significantly enhanced when the organic content (dry weight) is greater than 30 g·kg-1. The average migration amount of OPEs is 1077.3 ng·mL-1 at 27â, which was higher than that at 7â, indicating that high temperature promotes the release of OPEs. The effect of microorganisms is not notable. Chlorine-based OPEs including Tris(2-chloroethyl) phosphate (TCEP), Tris(1-chloro-2-propyl) phosphate (TCPP), and Tris(1,3-Dichloro-2-Propyl) phosphate (TDCP) are the main monomers in the overlying water, mainly because both the Octanol-Water Partition Coefficient (Kow) and Organic Carbon Partition Coefficient (Koc) of chlorine-based OPEs are lower than that of alkane-based OPEs and aromatic-based OPEs. Thus, chlorine-based OPEs are more easily dissolved in water and are not easily adsorbed by organic matter in the soil. Therefore, chlorine-based OPEs are more likely to migrate from the soil and to be released into the overlying water than other OPEs and become the main OPE monomers in the overlying water of the TGR.
RESUMEN
Currently, the HBCDs were listed in Annex A by the Stockholm Convention, and the knowledge on the contamination of TBBPA and HBCDs in soil and road dust in China is still limited, and it is unclear what role is played by dust particle size distribution. In this study, a total of 81 soil and 43 road dust samples were analyzed with TBBPA and ΣHBCDs concentrations ranging from < LOQ to 33.8â¯ng/g dw (dry weight) and 0.43-15.2â¯ng/g dw in soil, and from < LOQ to 74.1â¯ng/g dw and 7.25-14.0â¯ng/g dw in road dust, respectively. TBBPA and HBCDs exhibited different spatial distribution patterns in soil, where relatively high levels of HBCDs were found in industrial area and commercial area, while high levels of TBBPA were detceted in residential area. However, no distinct variation in spatial distribution of these two compounds was observed in road dust. Different diastereoisomer profiles of HBCDs were also found with γ-HBCD predominating in soil and α-HBCD occupying a large proportion in road dust. The α-/γ-HBCD values in road dust were significantly greater (T-test, Pâ¯<â¯0.05) than those in soil, which suggested that γ-HBCD in road dust were likely to transform into α-HBCD compared with soil. The distribution of dust particle size showed that HBCDs levels were increasing with the decreasing in particle sizes, while the TBBPA showed some "accidental" peak values in specific diameter ranges. The estimated daily intakes (EDIs) of TBBPA and HBCDs were assessed through dust ingestion, dermal absorption and inhalation via road dust, and all the exposure estimates were well below the reference dose (RfD), but the toddlers were more vulnerable to TBBPA and HBCDs intakes, which should be paid more attention.
Asunto(s)
Exposición a Riesgos Ambientales/análisis , Hidrocarburos Bromados/análisis , Bifenilos Polibrominados/análisis , Contaminantes del Suelo/análisis , China , Polvo/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Monitoreo del Ambiente , Retardadores de Llama/análisis , Humanos , Tamaño de la Partícula , SueloRESUMEN
Organophosphate esters (OPEs) in surface soil of four different functional areas in Chongqing were identified and quantified using ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS). The composition and characteristics of OPEs were discussed along with the relationships between soil organic matter (SOM) and OPEs through correlation analysis, and possible sources of OPEs were simultaneously investigated through principal component analysis (PCA). The results showed that the concentrations of ∑OPEs ranged from 10.7 to 108 ng·g-1 dry weight, with a mean concentration of 46.4 ng·g-1, which was at the low-level end of the global figure. The average concentration was 55.6 ng·g-1 in the industrial area, 55.5 ng·g-1 in the residential area, 41.8 ng·g-1 in the commercial area, and 34.1 ng·g-1 in the city park. Tris (1-chloro-2-propyl) phosphate (TCPP) and 2-ethylhexyl diphenyl phosphate (EHDPP) were dominant compounds, contributing up to 31.5% in the industrial area for TCPP and 23.4% and 24.7% in the commercial area and city park, respectively, for EHDPP. Significant relationships between concentrations of SOM and ∑OPEs (P<0.05) and tricresyl phosphate (TCP) (P<0.01), respectively, indicated that SOM was a factor affecting the concentration and distribution of the OPEs. The PCA suggested that there were multiple sources of OPEs in urban soil. Sewage irrigation, road runoff, indoor source pollution, and sludge reuse could be potential sources of soil OPEs.