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Drip irrigation with brackish water increases the risk of soil salinization while alleviating water shortage in arid areas. In order to alleviate soil salinity stress on crops, polymer soil amendments are increasingly used. But the regulation mechanism of a polymer soil amendment composed of polyacrylamide polyvinyl alcohol, and manganese sulfate (PPM) on rapeseed photosynthesis under drip irrigation with different types of brackish water is still unclear. In this field study, PPM was applied to study the responses of the rapeseed (Brassica napus L.) phenotype, photosynthetic physiology, transcriptomics, and metabolomics at the peak flowering stage under drip irrigation with water containing 6 g·L-1 NaCl (S) and Na2CO3 (A). The results showed that the inhibitory effect of the A treatment on rapeseed photosynthesis was greater than that of the S treatment, which was reflected in the higher Na+ content (73.30%) and lower photosynthetic-fluorescence parameters (6.30-61.54%) and antioxidant enzyme activity (53.13-77.10%) of the A-treated plants. The application of PPM increased the biomass (63.03-75.91%), photosynthetic parameters (10.55-34.06%), chlorophyll fluorescence parameters (33.83-62.52%), leaf pigment content (10.30-187.73%), and antioxidant enzyme activity (28.37-198.57%) under S and A treatments. However, the difference is that under the S treatment, PPM regulated the sulfur metabolism, carbon fixation and carbon metabolism pathways in rapeseed leaves. And it also regulated the photosynthesis-, oxidative phosphorylation-, and TCA cycle-related metabolic pathways in rapeseed leaves under A treatment. This study will provide new insights for the application of polymer materials to tackle the salinity stress on crops caused by drip irrigation with brackish water, and solve the difficulty in brackish water utilization.
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Brassica napus , Brassica rapa , Antioxidantes , Multiómica , Fotosíntesis , Productos Agrícolas , AguaRESUMEN
Hypoxic pulmonary hypertension (HPH) is a devastating disease worldwide; however, effective therapeutic drugs are lacking. This study investigated the effects and underlying mechanisms of LCZ696 treatment on hypoxia-induced pulmonary hypertension. Male Sprague-Dawley (SD) rats were kept in a hypobaric chamber with an oxygen concentration of 5% for 4 weeks. Rats were treated with either LCZ696 (18 mg/kg, 36 mg/kg, and 72 mg/kg) or sildenafil. The mean pulmonary artery pressure (mPAP), right ventricle hypertrophy index (RVHI), and lung system index were measured. Hematoxylin-eosin (HE) staining, Masson staining, and immunofluorescence staining were used for histological analysis. Enzyme linked immunosorbent assay (ELISA) kits were used to determine the concentrations of inflammatory and hypoxia-related factors. Western blotting was used to examine the expression of apoptotic and PI3K/AKT signaling pathway proteins in rat lung tissue. Hypoxia increased mPAP, RVHI, and lung system index and induced pulmonary vascular remodeling, pulmonary arteriomyosis, and pulmonary artery fibrosis. LCZ696 treatment reduced the increase in mPAP, RVHI, and the lung system index and ameliorated the induced pathological changes. Hypoxia upregulated expression of NF-kB, TNF-α, IL-6, HIF-1α, and Vascular endothelial growth factor (VEGF), decreased the ratio of Bax/Bcl-2, and activated the PI3K/AKT signaling pathway in lung tissue, and these effects were partially reversed by treatment with LCZ696. These results demonstrated that LCZ696 can ameliorate hypoxia-induced HPH by suppressing apoptosis, inhibiting the inflammatory response, and inhibiting the PI3K/AKT signaling pathway. It provides a reference for clinical rational drug use and lays a foundation for the study of HPH therapeutic drugs.
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Hipertensión Pulmonar , Fibrosis Pulmonar , Ratas , Masculino , Animales , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/prevención & control , Ratas Sprague-Dawley , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Hipoxia/metabolismo , Arteria Pulmonar/patología , Transducción de Señal , Fibrosis Pulmonar/patologíaRESUMEN
Manganese (Mn) intake has been found to be linked with risk of type 2 diabetes. However, the role of Mn in the development of gestational diabetes mellitus (GDM) remains to be investigated. This prospective study included pregnant women from the Tongji Maternal and Child Health Cohort. A total of 2327 participants with plasma specimens before 20 weeks were included. Among the pregnant women, 9.7% (225/2327) were diagnosed with GDM. After adjustment, pregnant women with the third and highest quartile of plasma Mn levels had 1.31-fold (RR, 2.31 [1.48, 3.61]) and 2.35-fold (RR, 3.35 [2.17, 5.17]) increased risk of GDM compared with those with the lowest quartile. A 1 standard deviation increment of ln-transformed plasma Mn levels (0.53 µg/L) was related to elevated risks of GDM with RRs of 1.28 [1.17, 1.40]. The positive associations between Mn and GDM remained consistent in all the subgroups. The weighted quantile sum index was significantly related to GDM (RR, 1.60 [1.37, 1.86]). The contribution of Mn (58.69%) to the metal mixture index was the highest related to GDM. Higher plasma Mn levels were found to be linked with elevated fasting and 2 h post-load blood glucose. This study revealed relationships of higher plasma Mn levels in early pregnancy and increased risk of GDM, suggesting that though essential, excess Mn in the body might be a potential important risk factor for GDM.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Niño , Femenino , Embarazo , Humanos , Diabetes Gestacional/epidemiología , Diabetes Gestacional/etiología , Estudios Prospectivos , Manganeso , Diabetes Mellitus Tipo 2/complicaciones , Glucemia , Factores de Riesgo , Estudios de CohortesRESUMEN
Some histone deacetylases (HDACs) promote tumor cell growth and pan- or selective HDAC inhibitors are active in some cancers; however, the pivotal HDAC enzyme and its functions in human diffuse large B-cell lymphoma (DLBCL) remain largely unknown. Using NanoString nCounter assays, we profiled HDAC mRNA expression and identified HDAC6 as an upregulated HDAC family member in DLBCL tissue samples. We then found that HDAC6 plays an oncogenic role in DLBCL, as evidenced by its promotion of cell proliferation in vitro and tumor xenograft growth in vivo. Mechanistically, the interaction between HDAC6 and HR23B downregulated HR23B expression, thereby reducing the levels of casitas B-lineage lymphoma (c-Cbl), an E3 ubiquitin ligase for hepatocyte growth factor receptor (MET), which resulted in the inhibition of MET ubiquitination-dependent degradation. In addition, enhanced HDAC6 expression and decreased HR23B expression were correlated with poor overall survival rates among patients with DLBCL. Taken together, these results establish an HDAC6-HR23B-MET axis and indicate that HDAC6 is a potent promoter of lymphomagenesis in DLBCL. Thus, a therapeutic strategy based on HDAC6 inhibitors in combination with MET inhibitors is promising. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Crizotinib/farmacología , Histona Desacetilasa 6/antagonistas & inhibidores , Inhibidores de Histona Desacetilasas/farmacología , Ácidos Hidroxámicos/farmacología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Pirimidinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Enzimas Reparadoras del ADN/metabolismo , Proteínas de Unión al ADN/metabolismo , Sinergismo Farmacológico , Femenino , Histona Desacetilasa 6/genética , Histona Desacetilasa 6/metabolismo , Humanos , Linfoma de Células B Grandes Difuso/enzimología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Proteolisis , Proteínas Proto-Oncogénicas c-cbl/metabolismo , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , Transducción de Señal/efectos de los fármacos , Carga Tumoral/efectos de los fármacos , Ubiquitinación , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We propose an ultraviolet broadband plasmonic absorber with dual narrow bands located separately in the visible and near-infrared regions. It employs a three-layer dielectric and metallic film structure based on a ring square nanodisk array. The interaction of surface plasmon resonance with a Fabry-Perot cavity resonance results in perfect absorption. The absorption efficiency is greater than 99.9% at wavelengths of 660 and 919 nm (visible and near-infrared), respectively, under normal incidence. In the ultraviolet region from 240 to 500 nm, absorption efficiency of over 90% can be achieved. The geometric symmetry of the ring square makes the perfect absorber polarization-independent and insensitive to large incident angle. This perfect absorber, which combines broadband and narrowband absorption, can be used as sensors, solar cells, or thermal emitters within one integrated device with further investigations.
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OBJECTIVE: To examine optimal gestational weight gain(GWG) for Chinese pregnant women. METHODS: A total of 6998 women with singleton and term pregnancy recruited to the Tongji Maternal and Child Health Cohort during January 2013 to May 2016 in Wuhan, Hubei were included. Information on sociodemographic, medical and family history of disease was obtained by questionnaire, body weight and height were measured at the first antenatal care during 8-16 weeks of gestation. Prenatal weight of mothers were measured, and gestational week, mode of delivery, pregnancy complications, gender of newborn, birth weight and length were collected from medical records after delivery. Restricted cubic spline was used to model nonlinear relationships between GWG and the occurrence of small for gestational age(SGA), large for gestational age(LGA), low birth weight(LBW), macrosomia, cesarean, gestational hypertension(GH)and gestational diabetes mellitus(GDM), respectively. The GWG of the lowest risks for adverse pregnant outcomes was regarded as optimal GWG recommended by Tongji(TJ) for pregnant women. The P25-P75 of GWG was defined as the optimal GWG recommended by percentile method. Logistic regression was used to analyze the effect of excessive or insufficient GWG on adverse pregnancy outcomes, while the recommendations of TJ and percentile method were used as references, respectively. RESULTS: (1) The GWG with lower risk of adverse pregnant outcomes based on pre-gravid body mass index(BMI) are 12. 0-17. 0 kg for underweight, 9. 0-14. 0 kg for normal weight and 7. 0-11. 0 kg for overweight, respectively, which are defined as TJ recommendations. The recommended GWG by percentile method are 14. 0-19. 0 kg for underweight, 13. 0-19. 0 kg for normal weight, 10. 8-18. 0 kg for overweight and 9. 0-15. 8 kg for obesity, respectively. (2) Compared to women gain within the TJ recommendations, OR of LGA is 2. 94(95%CI 2. 31-3. 73), macrosomia is 3. 13(95%CI 2. 38-4. 13), cesarean is 1. 53(95%CI 1. 38-1. 71) and GH is 2. 18(95%CI 1. 50-3. 17) for those with excessive GWG, OR of SGA is 1. 82(95%CI 1. 32-2. 53) for those who gain less. The corresponding ORs according to percentile method are 2. 11(95%CI 1. 76-2. 54) for LGA, 2. 16(95%CI 1. 76-2. 65) for macrosomia, 1. 53(95%CI 1. 36-1. 72) for cesarean, 1. 39(95%CI 1. 02-1. 90) for GH and 1. 60(95%CI 1. 29-1. 99) for SGA, respectively. CONCLUSION: The optimal GWG of Chinese pregnant women recommended by the study are 12. 0-17. 0 kg for pre-gravid underweight women, 9. 0-14. 0 kg for normal weight women and 7. 0-11. 0 kg for overweight, respectively.
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Ganancia de Peso Gestacional , Obesidad/fisiopatología , Sobrepeso/fisiopatología , Complicaciones del Embarazo/fisiopatología , Adolescente , Adulto , Peso al Nacer , Índice de Masa Corporal , Niño , China , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo , Población Urbana , Aumento de Peso , Adulto JovenRESUMEN
Background: Maternal iodine status has been suggested to affect birth outcomes. Few studies have focused on its effects on fetal growth during pregnancy. Objective: This study aimed to assess maternal iodine status during early pregnancy and further examine the relation between maternal iodine status and fetal growth. Methods: A total of 2087 singleton-pregnant women participating in the Tongji Maternal and Child Health Cohort study were involved. Urinary iodine concentration (UIC) and creatinine concentration were measured in spot urine samples collected in early pregnancy (<20 wk of gestation). Fetal head circumference (HC), femur length (FL), and estimated fetal weight (EFW) were evaluated by ultrasonography in each trimester. A multiple linear regression model was used to examine the association of iodine status with fetal growth characteristics, and a mixed-effects model was used to assess longitudinal effect. Results: The median UIC and iodine-to-creatinine (I/Cr) ratio were 178 µg/L and 234 µg/g, respectively. The prevalence of insufficient iodine status (I/Cr ratio <150 µg/g) was 19.8%(n = 414), of adequate iodine status (150-249 µg/g) was 34.8% (n = 726), of iodine status above the requirements (250-499 µg/g) was 32.1% (n = 669), and of excessive iodine status (≥500 µg/g) was 13.3% (n = 278). Maternal iodine insufficiency was inversely associated with fetal FL in the second and third trimesters. In stratified analysis, significant interactions were found between maternal iodine status and age as well as parity (all P < 0.05). The longitudinal analyses showed negative associations of maternal insufficient, more than adequate, or excessive iodine status with fetal growth during pregnancy (all P < 0.05). Conclusions: In central China, maternal iodine insufficiency and excess coexisted during early pregnancy and they both adversely affected fetal growth. There is an urgent need for ongoing monitoring of iodine status among vulnerable pregnant women in order to optimize iodine nutrition during pregnancy.
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Desarrollo Fetal/efectos de los fármacos , Yodo/administración & dosificación , Yodo/deficiencia , Fenómenos Fisiologicos de la Nutrición Prenatal , Adulto , China , Estudios de Cohortes , Femenino , Humanos , Masculino , Embarazo , Estudios ProspectivosRESUMEN
Maternal dietary patterns and macronutrients intake have been shown to affect the development of gestational diabetes mellitus (GDM), but the findings are inconsistent. We aimed to identify maternal dietary patterns and examine their associations with GDM risk, and to evaluate the contributions of macronutrients intake to these associations. We included 2755 Chinese pregnant women from the Tongji Maternal and Child Health Cohort. Dietary intakes were assessed using a validated semi-quantitative FFQ 2 weeks before the diagnosis of GDM. GDM (n 248) was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24-28 weeks gestation. We derived five different dietary patterns from a principal component analysis. The results showed that high fish-meat-eggs scores, which were positively related to protein intake and inversely related to carbohydrate intake, were associated with a higher risk of GDM (adjusted OR for quartile 4 v. quartile 1: 1·83; 95 % CI 1·21, 2·79; P trend=0·007) and higher plasma glucose levels. In contrast, high rice-wheat-fruits scores, which were positively related to carbohydrate intake and inversely related to protein intake, were associated with lower risk of GDM (adjusted OR for quartile 3 v. quartile 1: 0·54; 95 % CI 0·36, 0·83; P trend=0·010) and lower plasma glucose levels. In addition, dietary protein and carbohydrate intake significantly contributed to the associations between dietary patterns and GDM risk or glucose levels. These findings suggest that a dietary pattern characterised by high protein and low carbohydrate intake in pregnancy was associated with a higher risk of GDM, which may provide important clues for dietary guidance during pregnancy to prevent GDM.
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Diabetes Gestacional/prevención & control , Carbohidratos de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Glucemia/análisis , China , Dieta , Femenino , Frutas , Prueba de Tolerancia a la Glucosa , Humanos , Fenómenos Fisiologicos Nutricionales Maternos , Carne , Embarazo , Análisis de Componente Principal , Estudios Prospectivos , Riesgo , Factores de TiempoRESUMEN
Gold-coated nanodisk arrays of nearly micron periodicity are reported that have high figure of merit (FOM) and sensitivity necessary for plasmonic refractometric sensing, with the added benefit of suitability for surface-enhanced Raman scattering (SERS), large-scale microfabrication using standard photolithographic techniques and a simple instrumental setup. Gold nanodisk arrays are covered with a gold layer to excite the Bragg modes (BM), which are the propagative surface plasmons localized by the diffraction from the disk array. This generates surface-guided modes, localized as standing waves, leading to highly confined fields confirmed by a mapping of the SERS intensity and numerical simulations with 3D finite element method. The optimal gold-coated nanodisk arrays are applied for refractometric sensing in transmission spectroscopy with better performance than nanohole arrays and they are integrated to a 96-well plate reader for detection of IgY proteins in the nanometer range in PBS. The potential for sensing in biofluids is assessed with IgG detection in 1:1 diluted urine. The structure exhibits a high FOM of up to 46, exceeding the FOM of structures supporting surface plasmon polaritons and comparable to more complex nanostructures, demonstrating that subwavelength features are not necessary for high-performance plasmonic sensing.
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We present a dual-resonance fiber surface plasmon resonance (SPR) sensor for biological analysis. The sensing element was fabricated by sequentially sputtering layers of indium tin oxide (ITO) (100 nm thickness) and Au (35 nm thickness) on the surface of an optical fiber. The refractive index dispersion effect of ITO material led to resonances in the near infrared and visible wavelength regions. The refractive index of ITO is larger than the optical fiber in visible spectral area (400 to 733nm), such that the structure is a typical Kretschmann configuration surface plasmon resonance sensor. However, an Otto configuration is observed in the near infrared area (NIR) due to the ITO refractive index being smaller than the fiber core. We characterized the sensor performance by measuring bulk refractive index (RI) sensitivity in the two configurations, which were 1345 nm/RIU in the Kretschmann configuration and 1100 nm/RIU in the Otto configuration. In addition, this sensor was applied for real-time and label-free monitoring of the IgG/anti-IgG biomolecular interaction. As a robust and ultra-compact SPR sensor, which possesses wide detection range and is highly sensitive, this fiber SPR sensor can be applied for real-time biological analysis and monitoring.
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Técnicas Biosensibles , Resonancia por Plasmón de Superficie , Anticuerpos Antiidiotipos/análisis , Inmunoglobulina G/análisis , Fibras Ópticas , Refractometría , Compuestos de EstañoRESUMEN
In this work, a novel and simple optical fiber hot-wire anemometer based on single-walled carbon nanotubes (SWCNTs) coated tilted fiber Bragg grating (TFBG) is proposed and demonstrated. For the hot-wire wind speed sensor design, TFBG is an ideal in-fiber sensing structure due to its unique features. It is utilized as both light coupling and temperature sensing element without using any geometry-modified or uncommon fiber, which simplifies the sensor structure. To further enhance the thermal conversion capability, SWCNTs are coated on the surface of the TFBG instead of traditional metallic materials, which have excellent thermal characteristics. When a laser light is pumped into the sensor, the pump light propagating in the core will be easily coupled into cladding of the fiber via the TFBG and strongly absorbed by the SWCNTs thin film. This absorption acts like a hot-wire raising the local temperature of the fiber, which is accurately detected by the TFBG resonance shift. In the experiments, the sensor's performances were investigated and controlled by adjusting the inherent angle of the TFBG, the thickness of SWCNTs film, and the input power of the pump laser. It was demonstrated that the developed anemometer exhibited significant light absorption efficiency up to 93%, and the maximum temperature of the local area on the fiber was heated up to 146.1°C under the relatively low pump power of 97.76 mW. The sensitivity of -0.3667 nm/(m/s) at wind speed of 1.0 m/s was measured with the selected 12° TFBG and 1.6 µm film.
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Despite PIK3CD has been extensively reported in cancers, however, little evidence has been available regarding its role in the setting of diffuse large B cell lymphoma (DLBCL). In the present study, to investigate the role of PIK3CD in DLBCL, relevant experiments were carried out on both in vivo clinical tissue level and in vitro cell line level. Prognostic and clinicopathological significance were analyzed after immunohistochemical assay of PIK3CD expression on DLBCL tissue microarray. MTT assay and flow cytometry were employed to evaluate the proliferative variation, cell cycle, and apoptosis. Athymic nude mice xenografted with DLBCL cell line were employed to confirm the role of PIK3CD. It was found that there was a significant difference between expression of PIK3CD and international prognosis index (IPI), performance state (PS), and inferior overall prognosis. Furthermore, PIK3CD can promote proliferation and prevent apoptosis in DLBCL cells in vitro through upregulation of c-myc and p-AKT and in contrast downregulation of p21 and p27. In nude mice model, knock-down of PIK3CD was shown to be able to suppress the proliferation of DLBCL but not significantly compared with control group. Taken together, our study showed that PIK3CD can promote proliferation of DLBCL cells both in vitro and in vivo, suggesting that PIK3CD could be druggable in the therapy of DLBCL.
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Proliferación Celular , Fosfatidilinositol 3-Quinasa Clase I/biosíntesis , Linfoma de Células B Grandes Difuso/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Regulación hacia Arriba , Animales , Apoptosis/genética , Western Blotting , Ciclo Celular/genética , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasa Clase I/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Ratones Endogámicos NOD , Ratones Desnudos , Ratones SCID , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , Trasplante HeterólogoRESUMEN
Distinguishing hepatocellular carcinoma (HCC) from metastatic tumors is a challenging issue, especially in differential diagnosis between poorly differentiated HCC and metastasis tumors. Expression of Arg-1, HepPar-1, and α-fetoprotein (AFP) in 78 cases of HCC, 34 cases of metastatic tumors, and 228 cases of nonhepatocellular tumors of surgical specimens is measured by immunohistochemistry. Arg-1 immunoreactivity was detected in 75 of 78 (96.1 %) cases of HCC, whereas HepPar-1 and AFP immunoreactivity was detected in 63 of 78 (80.7 %) and 40 of 78 (51.3 %) cases of HCC, respectively. HepPar-1 and AFP expression was observed in three of 34 (8.8 %) cases and one of 34 (2.9 %) cases of metastatic tumors, respectively. In contrast, Arg-1 expression was absent in all 34 (0 %) cases of metastatic tumors. The sensitivity, specificity, positive predictive value, and negative predictive value of Arg-1 in distinguishing HCC from metastatic tumors and nonhepatocellular tumors are 96.1, 99.6, 98.7, and 98.8 % compared with 80.7, 92.0, 75.0, and 94.1 % for HepPar-1 and 51.3, 97.7, 87.0, and 87.1 % for AFP, respectively. Arg-1 is a more sensitive and better specific marker for HCC compared with HepPar-1 and AFP, indicating that Arg-1 can be easily applied in distinguishing HCC from metastatic tumors.
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Antígenos de Neoplasias/genética , Arginasa/biosíntesis , Carcinoma Hepatocelular/diagnóstico , Diagnóstico Diferencial , Neoplasias Hepáticas/diagnóstico , alfa-Fetoproteínas/biosíntesis , Adulto , Anciano , Arginasa/genética , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Pronóstico , alfa-Fetoproteínas/genéticaRESUMEN
BACKGROUND: It has been reported that the PI3K/AKT signaling pathway is activated in diffuse large B-cell lymphoma (DLBCL), PI3K constitutive activation plays a crucial role in PI3K/AKT pathway. However, the copy number variations (CNVs) of PI3K subunits on gene level remain unknown in DLBCL. Therefore, the aim of the study is to investigate the CNV of PI3K subunits and their relationship with clinicopathological features exploring the possible mechanism underlying of PI3K activation in DLBCL. METHODS: CNV of 12 genes in the PI3K/AKT pathway was detected by NanoString nCounter in 60 de novo DLBCLs and 10 reactive hyperplasia specimens as controls. Meanwhile, immunohistochemistry (IHC) was performed to examine the expression of p110α, p110ß, p110γ, p110δ, and pAKT on DLBCL tissue microarrays. RESULTS: All PI3K and AKT subunits, except for PIK3R1, had various CNVs in the form of copy number amplifications and copy number losses. Their rates were in the range of 8.3-20.0%. Of them PIK3CA and PIK3CB gene CNVs were significantly associated with decreased overall survival (P = 0.029 and P = 0.019, respectively). IHC showed that the frequency of strong positive expression of p110α, p110ß, p110γ, and p110δ were 26.7%, 25.0%, 18.3%, and 25.0% respectively, and they were found to be associated with decreased survival (P = 0.022, P = 0.015, P = 0.015, and P = 0.008, respectively). Expression of p110α was not only significantly associated with CNVs of PIK3CA (P = 0.002) but also positively correlated with strong positive expression of pAKT (P = 0.026). CONCLUSIONS: CNV of PIK3CA is highly associated with aberrant p110α protein expression and subsequent activation of PI3K/AKT pathway. CNVs of PIK3CA and PIK3CB, and aberrant protein expression of p110 isoforms are of great important value for predicting inferior prognosis in DLBCL. Frequent CNVs of PI3K/AKT subunits may play an important role in the tumorigenesis of DLBCL.
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Variaciones en el Número de Copia de ADN/genética , Linfoma de Células B Grandes Difuso/enzimología , Linfoma de Células B Grandes Difuso/genética , Fosfatidilinositol 3-Quinasas/genética , Subunidades de Proteína/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Fosfatidilinositol 3-Quinasa Clase I , Genes Relacionados con las Neoplasias , Predisposición Genética a la Enfermedad , Humanos , Inmunohistoquímica , Linfoma de Células B Grandes Difuso/patología , Subunidades de Proteína/genética , Transducción de Señal/genética , Análisis de Supervivencia , Análisis de Matrices TisularesRESUMEN
BACKGROUND: Extranodal nasal-type NK/T-cell lymphoma (ENKTCL) is a common and geographic predominant disease in China. We observed the clinical and pathologic features of this tumor type and its relationship to Epstein-Barr virus (EBV), and focused on the epidermology and prevalence of ENKTCL in Xinjiang, in order to improve the diagnostic and differential diagnosis ability. METHODS: 103 cases with nasal-type NK/T-cell lymphoma were recruited and assessed. All cases were submitted for histological assessment, immunophenotyping, in situ hybridization detection of EBV-encoded RNA (EBER), and clinical information analysis. RESULTS: Male patients, aged between 40 and 50 years, were predominantly of Han ethnicity outnumbering those of Uyghur ethnicity. 80 cases of ENKTCL involved the nasal cavity or other areas of the upper respirodigestive tract whereas the remaining ones involved other extranodal sites. All cases exhibited similar histological changes: necrosis and inflammatory infiltration were frequently present. Cytologic atypical as well as angiocentric and angiodestructive growth patterns of the tumor cells were consistently noted, although the sizes and contours of the tumor cells varied considerably. All cases expressed one or several T-cell markers and at least one cytotoxic molecule. 86 cases (84%) expressed CD56, and 97 cases submitted for EBER detection showed positive results. ENKTCL affects predominantly middle-aged Han Chinese in the Xinjiang region, with a predilection to involvement of the nasal cavity and a strong association with a high EBV load. CONCLUSIONS: Early and correct identification of the disease in daily practice depends on the combination of morphologic evaluation, immunophenotypic assessment, and EBER detection.
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Etnicidad , Inmunofenotipificación , Células Asesinas Naturales/inmunología , Linfoma de Células T/patología , Neoplasias Nasales/patología , Adulto , China , Femenino , Humanos , Hibridación in Situ , Linfoma de Células T/inmunología , Masculino , Persona de Mediana Edad , Neoplasias Nasales/inmunologíaRESUMEN
BACKGROUND: Small round blue-cell tumors (SRBCTs) of soft tissue, which mainly include rhabdomyosarcoma (RMS), synovial sarcoma (SS), and Ewing's sarcoma/peripheral primitive neuroectodermal tumors (EWS/ pPNETs), are malignancies with overlapping morphological and immunohistochemical characteristics. Immunohistochemistry is one of the most prevalent and convenient methods for pathological diagnosis; however, differentiation between SRBCT subtypes in the absence of valid diagnostic markers is still very challenging. The purpose of the present study was to investigate diagnostic immunohistochemistry for subtyping soft tissue SRBCTs. METHODS: Seventeen RMS, 25 SS, and 14 EWS/pPNETs were investigated. Reverse transcription RT-PCR and immunohistochemistry was performed to determine a diagnosis. Also, the expression of CD99, FLI1, PAX5, myogenin, and Keratin/EMA was assessed between subtypes. The sensitivity and specificity test was performed to evaluate their diagnostic significance. RESULTS: The sensitivity and specificity of the target markers were evaluated as follows. FLI1 and CD99 expression displayed strong associations in EWS/pPNETs, with OR (95% CI) and p values of 3.82 (1.23 - 11.94), p = 0.021 and 123.50 (12.63 - infinity), p < 0.001, respectively. Keratin/EMA expression did not support the diagnosis of EWS/pPNETs [OR (95% CI) = 0.06 (0.01 - 0.53), p = 0.011]. Myogenin expression displayed strong association with RMS, with high sensitivity and specificity of 94.1% and 100%, respectively. Membrane expression of CD99 did not support the diagnosis of RMS [OR (95% CI) = 0.09 (0.01 - 0.75), p = 0.026]. Keratin/EMA expression strongly indicated SS [OR (95% CI) = 345.00 (29.44 - infinity), p = 0.00011. A ROC curve value of 0.94 indicated that keratin/EMA expression might be a promising biomarker for SS, while separate expression of FLI1 and CD99 did not support the diagnosis of SS. Similarly, myogenin expression in RMS might be a promising biomarker for RMS with a ROC curve value of 0.97. CONCLUSIONS: Diagnosis of SRBCTs should be based on a comprehensive analysis involving morphology and immunoreactivity to a panel of markers.
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Inmunohistoquímica/métodos , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/metabolismo , Antígeno 12E7 , Adolescente , Adulto , Anciano , Antígenos CD/metabolismo , Moléculas de Adhesión Celular/metabolismo , Niño , Preescolar , Femenino , Humanos , Queratinas/metabolismo , Masculino , Persona de Mediana Edad , Tumores Neuroectodérmicos/diagnóstico , Tumores Neuroectodérmicos/metabolismo , Oportunidad Relativa , Proteína Proto-Oncogénica c-fli-1/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rabdomiosarcoma/diagnóstico , Rabdomiosarcoma/metabolismo , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/metabolismo , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/metabolismo , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Chinese fir (Cunninghamialanceolata) is a special fast-growing commercial tree species in China and has significant ecological and economic value. However, it experienced damage from leaf blight caused by pathogenic fungi of the genus Alternaria. To determine the diversity of Alternaria species associated with leaf blight of Chinese fir in China, infected leaves were collected from five major cultivation provinces (Fujian, Henan, Hunan, Jiangsu and Shandong provinces). A total of 48 fungal strains of Alternaria were obtained. Comparison of morphology and phylogenetic analyses, based on nine loci (ITS, SSU, LSU, GAPDH, RPB2, TEF1, Alt a1, endoPG and OPA10-2) of the representative isolates as well as the pairwise homoplasy index tests, revealed that the fungal strains belonged to seven undescribed taxa of Alternaria, which are described here and named as Alternariacunninghamiicolasp. nov., A.dongshanqiaoensissp. nov., A.hunanensissp. nov., A.kunyuensissp. nov., Ð. longqiaoensissp. nov., A.shandongensissp. nov. and A.xinyangensissp. nov. In order to prove Koch's postulates, pathogenicity tests on detached Chinese fir leaves revealed significant pathogenicity amongst these species, of which A.hunanensis is the most pathogenic to Chinese fir. This study represents the first report of A.cunninghamiicola, A.dongshanqiaoensis, A.hunanensis, A.kunyuensis, A.longqiaoensis, A.shandongensis and A.xinyangensis causing leaf blight on Chinese fir. Knowledge obtained in this study enhanced our understanding of Alternaria species causing leaf blight on Chinese fir and was crucial for the disease management and the further studies in the future.
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Seipin is a key regulator of lipid metabolism, the deficiency of which leads to severe lipodystrophy. Hypothalamus is the pivotal center of brain that modulates appetite and energy homeostasis, where Seipin is abundantly expressed. Whether and how Seipin deficiency leads to systemic metabolic disorders via hypothalamus-involved energy metabolism dysregulation remains to be elucidated. In the present study, we demonstrated that Seipin-deficiency induced hypothalamic inflammation, reduction of anorexigenic pro-opiomelanocortin (POMC), and elevation of orexigenic agonist-related peptide (AgRP). Importantly, administration of rosiglitazone, a thiazolidinedione antidiabetic agent, rescued POMC and AgRP expression, suppressed hypothalamic inflammation, and restored energy homeostasis in Seipin knockout mice. Our findings offer crucial insights into the mechanism of Seipin deficiency-associated energy imbalance and indicates that rosiglitazone could serve as potential intervening agent towards metabolic disorders linked to Seipin.
Asunto(s)
Proteína Relacionada con Agouti , Metabolismo Energético , Subunidades gamma de la Proteína de Unión al GTP , Homeostasis , Hipotálamo , Ratones Noqueados , Proopiomelanocortina , Rosiglitazona , Animales , Ratones , Hipotálamo/metabolismo , Metabolismo Energético/efectos de los fármacos , Proopiomelanocortina/genética , Proopiomelanocortina/biosíntesis , Proteína Relacionada con Agouti/genética , Subunidades gamma de la Proteína de Unión al GTP/genética , Rosiglitazona/farmacología , Masculino , Enfermedades Neuroinflamatorias/etiología , Ratones Endogámicos C57BL , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Neuropéptidos/genética , Neuropéptidos/deficiencia , Regulación de la Expresión Génica/efectos de los fármacosRESUMEN
Chinese fir (Cunninghamialanceolata) is a special fast-growing commercial tree species in China with high economic value. In recent years, leaf blight disease on C.lanceolata has been observed frequently. The diversity of Fusarium species associated with leaf blight on C.lanceolata in China (Fujian, Guangxi, Guizhou, and Hunan provinces) was evaluated using morphological study and molecular multi-locus analyses based on RNA polymerase second largest subunit (RPB2), translation elongation factor 1-alpha (TEF-1α), and RNA polymerase largest subunit (RPB1) genes/region as well as the pairwise homoplasy index tests. A total of five Fusarium species belonging to four Fusarium species complexes were recognized in this study. Two known species including Fusariumconcentricum and F.fujikuroi belonged to the F.fujikuroi species complex, and three new Fusarium species were described, i.e., F.fujianense belonged to the F.lateritium species complex, F.guizhouense belonged to the F.sambucinum species complex, and F.hunanense belonged to the F.solani species complex. To prove Koch's postulates, pathogenicity tests on C.lanceolata revealed a wide variation in pathogenicity and aggressiveness among the species, of which F.hunanense HN33-8-2 caused the most severe symptoms and F.fujianense LC14 led to the least severe symptoms. To our knowledge, this study also represented the first report of F.concentricum, F.fujianense, F.fujikuroi, F.guizhouense, and F.hunanense causing leaf blight on C.lanceolata in China.
RESUMEN
Drought poses a serious challenge to sustained plant growth and crop yields in the context of global climate change. Drought tolerance in poplars and their underlying mechanisms still remain largely unknown. In this article, we investigated the overexpression of PtoMYB99 - both a drought and abscisic acid (ABA) induced gene constraining drought tolerance in poplars (as compared with wild type poplars). First, we found that PtoMYB99-OE lines exhibited increased stomatal opening and conductance, higher transpiration and photosynthetic rates, as well as reduced levels of ABA and jasmonic acid (JA). Second, PtoMYB99-OE lines accumulated more reactive oxygen species (ROS), including H2O2 and O2-, as well as malonaldehyde (MDA), proline, and soluble sugar under osmotic stress; conversely, the activity of antioxidant enzymes (SOD, POD, and CAT), was weakened in the PtoMYB99-OE lines. Third, the expression of ABA biosynthetic genes, PtoNCED3.1 and PtoNCED3.2, as well as JA biosynthetic genes, PtoOPR3.1 and PtoOPR3.2, was significantly reduced in the PtoMYB99-OE lines under both normal conditions and osmotic stress. Based on our results, we conclude that the overexpression of PtoMYB99 compromises tolerance to osmotic stress in poplar. These findings contribute to the understanding of the role of the MYB genes in drought stress and the biosynthesis of ABA and JA.