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OBJECTIVES: To explore the potential of radiomics features to predict the histologic grade of nonfunctioning pancreatic neuroendocrine tumor (NF-PNET) patients using non-contrast sequence based on MRI. METHODS: Two hundred twenty-eight patients with NF-PNETs undergoing MRI at 5 centers were retrospectively analyzed. Data from center 1 (n = 115) constituted the training cohort, and data from centers 2-5 (n = 113) constituted the testing cohort. Radiomics features were extracted from T2-weighted images and the apparent diffusion coefficient. The least absolute shrinkage and selection operator was applied to select the most important features and to develop radiomics signatures. The area under receiver operating characteristic curve (AUC) was performed to assess models. RESULTS: Tumor boundary, enhancement homogeneity, and vascular invasion were used to construct the radiological model to stratify NF-PNET patients into grade 1 and 2/3 groups, which yielded AUC of 0.884 and 0.684 in the training and testing groups. A radiomics model including 4 features was constructed, with an AUC of 0.941 and 0.871 in the training and testing cohorts. The fusion model combining the radiomics signature and radiological characteristics showed good performance in the training set (AUC = 0.956) and in the testing set (AUC = 0.864), respectively. CONCLUSION: The developed model that integrates radiomics features with radiological characteristics could be used as a non-invasive, dependable, and accurate tool for the preoperative prediction of grade in NF-PNETs. CLINICAL RELEVANCE STATEMENT: Our study revealed that the fusion model based on a non-contrast MR sequence can be used to predict the histologic grade before operation. The radiomics model may be a new and effective biological marker in NF-PNETs. KEY POINTS: The diagnostic performance of the radiomics model and fusion model was better than that of the model based on clinical information and radiological features in predicting grade 1 and 2/3 of nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs). Good performance of the model in the four external testing cohorts indicated that the radiomics model and fusion model for predicting the grades of NF-PNETs were robust and reliable, indicating the two models could be used in the clinical setting and facilitate the surgeons' decision on risk stratification. The radiomics features were selected from non-contrast T2-weighted images (T2WI) and diffusion-weighted imaging (DWI) sequence, which means that the administration of contrast agent was not needed in grading the NF-PNETs.
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Tumores Neuroectodérmicos Primitivos , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Clasificación del Tumor , Tumores Neuroendocrinos/diagnóstico por imagen , Estudios Retrospectivos , Radiómica , Imagen por Resonancia Magnética/métodos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patologíaRESUMEN
Two-dimensional room-temperature intrinsic ferromagnetic semiconductors have attracted widespread attention due to their applications in spintronic devices. However, it is difficult for the material to have a Curie temperature above room temperature according to the Mermin-Wagner theorem. By using the method of band engineering, we design a new promising two-dimensional room-temperature intrinsic ferromagnetic semiconductor Cr2XP (X = P, As, Sb) with large magnetization. The formation of a semiconducting gap for Cr2XP is discussed in terms of hybridization, occupation and distribution of electronic states and charge transfer. Large magnetic moments of about 6.16-6.37µB originate from the occupation of Cr-d electrons in the crystal field. Competition between Cr-d-Cr-d and Cr-d-X-p-Cr-d exchange interactions leads to the emergence of a ferromagnetic order phase. Furthermore, Curie temperatures, approaching 278 K, 464 K and 1590 K for Cr2P2, Cr2AsP and Cr2SbP, are estimated by employing Monte Carlo simulations based on the Heisenberg model. The magnetic anisotropy energy of Cr2XP is discussed using magnetic second-order perturbation theory. In addition, Cr2XP possesses excellent thermodynamic, dynamical, thermal and mechanical stabilities and can overcome its own gravity to retain its planar structure without the support of the substrate. These above-mentioned advantages will offer some valuable insights into two-dimensional intrinsic ferromagnetic semiconductor Cr2XP in spintronic devices.
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BACKGROUND: Hypercholesterolemia is one of the risk factors for colorectal cancer (CRC). Cholesterol can participate in the regulation of human T cell function and affect the occurrence and development of CRC. OBJECTIVE: To elucidate the pathogenesis of CRC immune escape mediated by CD8+ T cell exhaustion induced by cholesterol. METHODS: CRC samples (n = 217) and healthy individuals (n = 98) were recruited to analyze the relationship between peripheral blood cholesterol levels and the clinical features of CRC. An animal model of CRC with hypercholesterolemia was established. Intraperitoneal intervention with endoplasmic reticulum stress (ERS) inhibitors in hypercholesterolemic CRC mice was performed. CD69, PD1, TIM-3, and CTLA-4 on CD8+ T cells of spleens from C57BL/6 J mice were detected by flow cytometry. CD8+ T cells were cocultured with MC38 cells (mouse colon cancer cell line). The proliferation, apoptosis, migration and invasive ability of MC38 cells were detected by CCK-8 assay, Annexin-V APC/7-AAD double staining, scratch assay and transwell assay, respectively. Transmission electron microscopy was used to observe the ER structure of CD8+ T cells. Western blotting was used to detect the expression of ERS and mitophagy-related proteins. Mitochondrial function and energy metabolism were measured. Immunoprecipitation was used to detect the interaction of endoplasmic reticulum-mitochondria contact site (ERMC) proteins. Immunofluorescence colocalization was used to detect the expression and intracellular localization of ERMC-related molecules. RESULTS: Peripheral blood cholesterol-related indices, including Tc, low density lipoproteins (LDL) and Apo(a), were all increased, and high density lipoprotein (HDL) was decreased in CRCs. The proliferation, migration and invasion abilities of MC38 cells were enhanced, and the proportion of tumor cell apoptosis was decreased in the high cholesterol group. The expression of IL-2 and TNF-α was decreased, while IFN-γ was increased in the high cholesterol group. It indicated high cholesterol could induce exhaustion of CD8+ T cells, leading to CRC immune escape. Hypercholesterolemia damaged the ER structure of CD8+ T cells and increased the expression of ER stress molecules (CHOP and GRP78), lead to CD8+ T cell exhaustion. The expression of mitophagy-related proteins (BNIP3, PINK and Parkin) in exhausted CD8+ T cells increased at high cholesterol levels, causing mitochondrial energy disturbance. High cholesterol enhanced the colocalization of Fis1/Bap31, MFN2/cox4/HSP90B1, VAPB/PTPIP51, VDAC1/IPR3/GRP75 in ERMCs, indicated that high cholesterol promoted the intermolecular interaction between ER and mitochondrial membranes in CD8+ T cells. CONCLUSION: High cholesterol regulated the ERS-ERMC-mitophagy axis to induce the exhaustion of CD8+ T cells in CRC.
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Neoplasias Colorrectales , Hipercolesterolemia , Humanos , Animales , Ratones , Membranas Asociadas a Mitocondrias , Linfocitos T CD8-positivos/metabolismo , Hipercolesterolemia/metabolismo , Agotamiento de Células T , Ratones Endogámicos C57BL , Colesterol , Mitocondrias/metabolismo , Neoplasias Colorrectales/patología , Estrés del Retículo Endoplásmico , Apoptosis , Proteínas Tirosina Fosfatasas/metabolismoRESUMEN
We report the case of a 41-year-old human with third-degree atrioventricular block caused due to intoxication with water concoction prepared from Rhododendron leaves. Such poisoning is rare. It is prone to arrhythmia with hemodynamic instability and is confused with various diseases. For these reasons, the correct diagnosis and treatment of this poisoning are particularly important. We confirmed it by analyzing the remaining liquid carried by the family members. After symptomatic and supportive treatment, the patient was discharged uneventfully.
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Bloqueo Atrioventricular , Miel , Rhododendron , Humanos , Adulto , Bloqueo Atrioventricular/inducido químicamente , Bloqueo Atrioventricular/diagnóstico , Bloqueo Atrioventricular/terapia , Miel/análisis , Electrocardiografía , Hojas de la PlantaRESUMEN
Rhodotorula mucilaginosa resists heavy metal (HM) stress because of its abundant extracellular polymeric substances and functional vesicles. In this study, we provided new insights into its survival strategies at both biochemical and genetic levels. After lead exposure, carotenoid biosynthesis was initiated within 24 h incubation and then increased to the maximum after 96 h of incubation. Raman analysis confirmed that carotenoids (primarily ß-carotene) were the major identifiable chemical substances on the cell surface. Moreover, the increased carotenoid production was accompanied by a rising budding rate, ~40% higher than that in the cultures without Pb. During the 96 h of incubation, the driving force for Pb accumulation was assigned to this elevated budding rate. After 96 h, biosorption was primarily attributed to the enhanced antioxidant ability of the single cells during carotenoid production. Furthermore, the yeast budding cells demonstrated an evidently heterogeneous biosorption of Pb, i.e., the rejuvenated daughters had a relatively lower Pb level than the mother cells. This resulted in the protection of the buds from Pb stress. After investigating phosphorus uptake and the RNA sequencing data, we finally confirmed two tightly correlated pathways that resist HM stress, i.e., biochemical (carotenoid production) and reproductive (healthy buds) pathways.
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Plomo , Rhodotorula , Carotenoides/metabolismo , Rhodotorula/genética , Rhodotorula/metabolismo , beta CarotenoRESUMEN
BACKGROUND: The mortality of colorectal cancer is high, the malignant degree of poorly differentiated colorectal cancer is high, and the prognosis is poor. OBJECTIVE: To screen the characteristic intestinal microbiota of poorly differentiated intestinal cancer. METHODS: Fecal samples were collected from 124 patients with moderately differentiated CRC and 123 patients with poorly differentiated CRC, and the bacterial 16S rRNA V1-V4 region of the fecal samples was sequenced. Alpha diversity analysis was performed on fecal samples to assess the diversity and abundance of flora. The RDP classifier Bayesian algorithm was used to analyze the community structure. Linear discriminant analysis and Student's t test were used to screen the differences in flora. The PICRUSt1 method was used to predict the bacterial function, and six machine learning models, including logistic regression, random forest, neural network, support vector machine, CatBoost and gradient boosting decision tree, were used to construct a prediction model for the poor differentiation of colorectal cancer. RESULTS: There was no significant difference in fecal flora alpha diversity between moderately and poorly differentiated colorectal cancer (P > 0.05). The bacteria that accounted for a large proportion of patients with poorly differentiated and moderately differentiated colorectal cancer were Blautia, Escherichia-Shigella, Streptococcus, Lactobacillus, and Bacteroides. At the genus level, there were nine bacteria with high abundance in the poorly differentiated group, including Bifidobacterium, norank_f__Oscillospiraceae, Eisenbergiella, etc. There were six bacteria with high abundance in the moderately differentiated group, including Megamonas, Erysipelotrichaceae_UCG-003, Actinomyces, etc. The RF model had the highest prediction accuracy (100.00% correct). The bacteria that had the greatest variable importance in the model were Pseudoramibacter, Megamonas and Bifidobacterium. CONCLUSION: The degree of pathological differentiation of colorectal cancer was related to gut flora, and poorly differentiated colorectal cancer had some different bacterial flora, and intestinal bacteria can be used as biomarkers for predicting poorly differentiated CRC.
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Neoplasias Colorrectales , Microbioma Gastrointestinal , Humanos , Neoplasias Colorrectales/microbiología , ARN Ribosómico 16S/genética , Teorema de Bayes , Bacterias/genética , Microbioma Gastrointestinal/genética , Heces/microbiologíaRESUMEN
Long non-coding RNAs (lncRNAs) contribute to disease pathogenesis and drug treatment effects. Both emodin and dexamethasone (DEX) have been used for treating severe acute pancreatitis-associated acute lung injury (SAP-ALI). However, lncRNA regulation networks related to SAP-ALI pathogenesis and drug treatment are unreported. In this study, lncRNAs and mRNAs in the lung tissue of SAP-ALI and control rats, with or without drug treatment (emodin or DEX), were assessed by RNA sequencing. Results showed both emodin and DEX were therapeutic for SAP-ALI and that mRNA and lncRNA levels differed between untreated and treated SAP-ALI rats. Gene expression profile relationships for emodin-treated and control rats were higher than DEX-treated and -untreated animals. By comparison of control and SAP-ALI animals, more up-regulated than down-regulated mRNAs and lncRNAs were observed with emodin treatment. For DEX treatment, more down-regulated than up-regulated mRNAs and lncRNAs were observed. Functional analysis demonstrated both up-regulated mRNA and co-expressed genes with up-regulated lncRNAs were enriched in inflammatory and immune response pathways. Further, emodin-associated lncRNAs and mRNAs co-expressed modules were different from those associated with DEX. Quantitative polymerase chain reaction demonstrates selected lncRNA and mRNA co-expressed modules were different in the lung tissue of emodin- and DEX-treated rats. Also, emodin had different effects compared with DEX on co-expression network of lncRNAs Rn60_7_1164.1 and AABR07062477.2 for the blue lncRNA module and Nrp1 for the green mRNA module. In conclusion, this study provides evidence that emodin may be a suitable alternative or complementary medicine for treating SAP-ALI.
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Lesión Pulmonar Aguda/etiología , Emodina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Redes Reguladoras de Genes/efectos de los fármacos , Pancreatitis/complicaciones , ARN Largo no Codificante/genética , ARN Mensajero/genética , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Animales , Biomarcadores , Biopsia , Biología Computacional/métodos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Ontología de Genes , Mediadores de Inflamación/metabolismo , Masculino , RatasRESUMEN
A novel series of 2-styryl-5-hydroxy-4-pyrone derivatives and analogues were designed and synthesized as H3 receptor antagonism based multitarget-directed ligands (MTDLs) for AD therapy using pharmacophore-combine strategy. The 2-styryl-5-hydroxy-4-pyrone pharmacophore with metal ion chelation, antioxidation, and Aß aggregation inhibition activities was employed as the "eastern part", and a typical phenoxyalkylamine moiety was used as "central ring + western part" of the H3 receptor antagonist. The biological evaluation revealed that the majority of the target compounds demonstrated desirable multiple functions. The two most promising compounds 8a and 8b exhibited nanomolar IC50 values on H3 receptor antagonism, excellent metal ion chelating capability, more potent ABTS+ scavenging activity than Trolox, efficient Aß self-aggregation and Cu2+-induced aggregation inhibitory activities, as well as disaggregation activities against Aß self/Cu2+-induced aggregation.
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Enfermedad de Alzheimer/tratamiento farmacológico , Antioxidantes/farmacología , Diseño de Fármacos , Pironas/farmacología , Receptores Histamínicos H3/metabolismo , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/metabolismo , Antioxidantes/síntesis química , Antioxidantes/química , Benzotiazoles/antagonistas & inhibidores , Cobre/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Agregado de Proteínas/efectos de los fármacos , Pironas/síntesis química , Pironas/química , Relación Estructura-Actividad , Ácidos Sulfónicos/antagonistas & inhibidoresRESUMEN
BACKGROUND In controlled ovarian hyperstimulation protocols worldwide, depot gonadotropin-releasing hormone agonist (GnRH-a) pretreatment is generally used for pituitary desensitization. The delay between the GnRH-a administration and starting gonadotropin treatment varies greatly, from 25 to 60 days. However, the association between exposure days to GnRH-a before the onset of gonadotropin administration and the clinical outcomes remains unknown. MATERIAL AND METHODS This retrospective study included 7007 patients who underwent fresh embryo transfers between February 2016 and July 2019. The duration of pituitary downregulation was categorized into 3 groups: group 1, ≤30 days; group 2, 31-35 days; and group 3, ≥36 days. The rates of live birth were compared as the main outcome measure. Logistic regression analysis was also performed after controlling for a range of confounders. RESULTS The number of patients in groups 1, 2, and 3 was 2001, 2824, and 2182, respectively. Group 3 (≥36 days) had a noticeably higher live birth rate (48.1%) than the other 2 groups (42.6% and 43.9%, P=0.001). The rate of live birth was remarkably enhanced in group 3 (adjusted odds ratio: 1.264, 95% confidence interval: 1.098, 1.455, P=0.001) after controlling for confounders, while the difference was not found in group 2 (P=0.512) compared with group 1. CONCLUSIONS In the depot GnRH-a protocol, live birth rates are higher among patients needing a longer time to achieve the goal of pituitary downregulation.
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Hormona Liberadora de Gonadotropina/agonistas , Nacimiento Vivo/epidemiología , Hipófisis/fisiología , Embarazo , Adulto , Tasa de Natalidad , Gonadotropina Coriónica/metabolismo , Transferencia de Embrión , Femenino , Hormona Liberadora de Gonadotropina/metabolismo , Humanos , Inducción de la Ovulación/métodos , Inducción de la Ovulación/estadística & datos numéricos , Índice de Embarazo , Estudios RetrospectivosRESUMEN
Successful application of microorganisms to heavy metal remediation depends on their resistance to toxic metals. This study contrasted the differences of tolerant mechanisms between Pb2+ and Cd2+ in Enterobacter sp. Microbial respiration and production of formic acid showed that Enterobacter sp. had a higher tolerant concentration of Pb (>1000 mg l-1 ) than Cd (about 200 mg l-1 ). Additionally, SEM confirmed that most of Pb and Cd nanoparticles (NPs) were adsorbed onto cell membrane. The Cd stress, even at low concentration (50 mg l-1 ), significantly enlarged the sizes of cells. The cellular size raised from 0.4 × 1.0 to 0.9 × 1.6 µm on average, inducing a platelet-like shape. In contrast, Pb cations did not stimulate such enlargement even up to 1000 mg l-1 . Moreover, Cd NPs were adsorbed homogeneously by almost all the bacterial cells under TEM. However, only a few cells work as 'hot spots' on the sorption of Pb NPs. The heterogeneous sorption might result from a 'self-sacrifice' mechanism, i.e., some cells at a special life stage contributed mostly to Pb sorption. This mechanism, together with the lower mobility of Pb cations, caused higher microbial tolerance and removal efficiency towards Pb2+ . This study sheds evident contrasts of bacterial resistance to the two most common heavy metals.
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Cadmio/toxicidad , Enterobacter/efectos de los fármacos , Plomo/toxicidad , Nanopartículas del Metal/toxicidad , Adsorción , Cadmio/química , Membrana Celular/química , Tamaño de la Célula/efectos de los fármacos , Enterobacter/química , Enterobacter/metabolismo , Enterobacter/ultraestructura , Formiatos/metabolismo , Plomo/química , Nanopartículas del Metal/química , Microscopía Electrónica de Transmisión , Estrés FisiológicoRESUMEN
Cardiovascular disease (CVD) is the leading cause of death among patients in China, and cardiac computed tomography (CT) is one of the most commonly used examination methods for CVD. Coronary artery CT angiography can be used for the morphologic evaluation of the coronary artery. At present, cardiac CT functional imaging has become an important direction of development of CT. At present, common CT functional imaging technologies include transluminal attenuation gradient, stress dynamic CT myocardial perfusion imaging, and CT-fractional flow reserve. These three imaging modes are introduced and analyzed in this review.
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Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , China , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Humanos , Valor Predictivo de las Pruebas , Tecnología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The aim of this study was to explore the correlation between serum vitamin D levels in couples undergoing in-vitro fertilisation (IVF) and normal fertilisation process. METHODS: Between March 2016 and March 2017, we performed a prospective cohort study at an academic reproductive medicine centre to measure serum 25-hydroxyvitaminD (25-OHD) levels of 1232 couples before controlled ovarian stimulation. Generalized linear regression and binary multivariate logistic regression were employed to assess whether 25-OHD levels in men and women correlated with normal fertilisation rates and low fertilisation rate (LFR). RESULTS: Serum 25-OHD levels in women were classified into three groups: Group A, less than 10%; Group B, between 10 and 90%; and Group C, greater than 90%. Using generalized linear regression, we observed that female 25-OHD levels were related to normal fertilisation rates. Adjusted normal fertilisation rates from Group A to Group C in women were 59.50, 62.72, and 66.13%, respectively (P = 0.007). After binary logistic regression analysis, for women, compared with Group C, the ORs for LFR were 4.814 in Group A (95% CI, 1.266-18.309, P = 0.021) and were 3.204 in Group B (95% CI, 0.949-10.812, P = 0.061). Male 25-OHD levels were not related to the probability of low fertilisation rate (P > 0.05). CONCLUSIONS: Circulating 25-OHD concentrations in women appear to be associated with normal fertilisation rates and low fertilisation rates in IVF cycles, but not in men. A further randomized controlled trial with vitamin D supplementation is needed to demonstrate whether female vitamin D levels exert an effect on the normal fertilisation process. TRIAL REGISTRATION: https://clinicaltrials.gov/;NCT03305510; Registered 08 October 2017 - Retrospectively registered.
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Fertilización In Vitro , Fertilización , Vitamina D/sangre , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Inducción de la Ovulación , Estudios Prospectivos , Adulto JovenRESUMEN
Environmental microorganisms have been widely applied in heavy metal remediation. This study explored the mechanisms of lead tolerance of two typical filamentous fungi, Aspergillus niger and Penicillium oxalicum. It is shown that the mechanisms of reducing Pb toxicity by these two fungi have three major pathways. The secreted oxalic acid can react with Pb (II) to form insoluble Pb minerals, primarily lead oxalate. Then, the enhanced biosorption via forming new border of cell wall prevents the transportation of Pb (II) into hypha. In addition, the fungal activity could be maintained even at high Pb concentration due to the intracellular accumulation. It was confirmed that A. niger has the higher Pb tolerance (up to 1500 mg l-1 Pb level) compared with P. oxalicum (up to 1000 mg l-1 ). Meanwhile, Pb levels below 1000 mg l-1 partially stimulate the bioactivity of A. niger, which was confirmed by its elevated respiration (from 53 to 63 mg C l-1 medium h-1 ). This subsequently enhanced microbial functions of A. niger to resist Pb toxicity. A better understanding of Pb tolerance of these two fungi sheds a bright future of applying them to remediate lead-contaminated environments.
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Aspergillus niger/metabolismo , Biodegradación Ambiental , Plomo/toxicidad , Ácido Oxálico/metabolismo , Penicillium/metabolismo , Aspergillus niger/efectos de los fármacos , Minerales/metabolismo , Oxalatos/metabolismo , Penicillium/efectos de los fármacosRESUMEN
RESEARCH QUESTION: Do serum vitamin D levels in men and women undergoing IVF/intracytoplasmic sperm injection (ICSI) affect embryo development and clinical outcomes? DESIGN: A large retrospective observational cohort study conducted between March 2016 and March 2017; plasma 25-OHD levels were measured before ovarian stimulation in couples undergoing IVF/ICSI (including 1883 women and 1720 men). RESULTS: Women were divided into four groups in terms of serum 25-OHD quartiles: <14.8 ng/ml (Q1), 14.8-19.6 ng/ml (Q2), 19.7-24.7 ng/ml (Q3) or >24.7 ng/ml (Q4). Statistically significant differences in top-quality embryo rates were found among different groups on Day 3 (Pâ¯=â¯0.016) but not on Day 2 or Day 5/6. Specifically, the top-quality embryo rate on Day 3 was highest in Q2, a statistically significant difference compared with Q3 (Pâ¯=â¯0.014). The multiple linear regression showed that serum 25-OHD levels in women were not significantly related to top-quality embryo rates on Day 2, Day 3 or Day 5/6. There were no differences in implantation, clinical pregnancy, miscarriage and live birth rates among the groups. Logistic regression revealed that there were no significant differences in the success of clinical pregnancy. In men, no significant association was found between vitamin D status and embryo development or clinical outcomes. CONCLUSIONS: In neither men nor women were vitamin D levels associated with embryo development in cleavage (Day 2 and Day 3) and blastocyst (Day 5/6) stage and clinical outcomes. This may be because the threshold of vitamin D affecting the reproductive process is relatively low; a multicentre study in a high-latitude region is needed.
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Desarrollo Embrionario , Técnicas Reproductivas Asistidas/estadística & datos numéricos , Vitamina D/análogos & derivados , Adulto , Femenino , Humanos , Masculino , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Vitamina D/sangre , Adulto JovenRESUMEN
Microorganisms have been widely applied to heavy metal adsorption due to their strong secretion of extracellular polymeric substances (EPS). This study explored the responses of Rhodotorula mucilaginosa (R1, a red yeast with substantial EPS supply) under Pb stress. The maximum sorption of Pb cations by R1 was ~650â¯mg/L. In particular, despite the declined microbial biomass, the total Pb sorption after incubation was actually elevated in the solution with high Pb concentration. At 0-1000â¯mg/L Pb(NO3)2 level, the longitudinal sizes of the yeast capsules increased from 2.04 to 2.90⯵m. At 1500â¯mg/L, however, the survived yeast started to lose the membrane integrity of the cells. Meanwhile, the percentages of organic carbon contents of EPS decreased from 40% to 33% when the Pb(NO3)2 concentration raised to 2500â¯mg/L, confirming the incorporation of Pb2+ cations into the fungal EPS during the sorption. For the survived R1 cells, function of polysaccharides to resist Pb toxicity only worked at extremely high Pb(NO3)2 levels (>=â¯1500â¯mg/L). In contrast, proteins showed continuously enhanced ability to resist Pb toxicity, consistent with their increasing content (per cell) in the EPS. Moreover, ATR-IR spectra showed that the intensity of amide II peak at 1540â¯cm-1 was significantly increased, indicating elevated glutathione (GSH) in EPS. This suggested that GSH could be the critical Pb-binding component in EPS proteins. This study hence elucidated roles of polysaccharides and proteins in EPS under the toxicity caused by heavy metals.
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Contaminantes Ambientales/toxicidad , Matriz Extracelular de Sustancias Poliméricas/metabolismo , Proteínas Fúngicas/metabolismo , Plomo/toxicidad , Polisacáridos/metabolismo , Rhodotorula/efectos de los fármacos , Adsorción , Biomasa , Contaminantes Ambientales/metabolismo , Plomo/metabolismo , Estrés Oxidativo/efectos de los fármacos , Rhodotorula/crecimiento & desarrollo , Rhodotorula/metabolismo , Rhodotorula/ultraestructuraRESUMEN
Decidualization is regulated by crosstalk of progesterone and the cAMP pathway. It involves extensive reprogramming of gene expression and includes a wide range of functions. To investigate how cell cycle regulatory genes drive the human endometrial stromal cell (ESC) exit cell cycle and enter differentiation, primary cultured ESC was treated with 8-Br-cAMP and MPA and cell cycle distribution was investigated by flow cytometry. High-throughput cell cycle regulatory gene expression was also studied by microarray. To validate the results of microarray chip, immunohistochemistry and semi-quantitative method of optical density were used to analyze the expression of cell cycle regulator proteins in proliferative phase of endometrium (n = 6) and early pregnancy decidua (n = 6). In addition, we selected cyclin-dependent kinase inhibitor 1c (CDKN1C, also known as P57) and cyclin-dependent kinase inhibitor 2b (CDKN2B, also known as P15) in order to study their role in the process of decidualization by the RNAi method. ESC was arrested at G0/G1 checkpoints during decidualization. Cell cycle regulatory genes P57 and P15 were upregulated, while cyclin D1 (CCND1), cyclin-dependent kinase 2 (CDK2), and cell division cycle protein 2 homolog (CDC2) were downregulated during ESC differentiation both in vitro and vivo. P57 siRNA impaired ESC decidualization and caused different morphological and ultrastructural changes as well as a relatively low secretion of prolactin, but P15 siRNA had no effects. We concluded that P15, CCND1, CDK2, and CDC2 may participate in ESC withdraw from the cell cycle and go into differentiation both in vitro and in vivo. P57 is one of the key determinants of ESC differentiation due to its effect on the cell cycle distribution, but its association with the decidua-specific transcription factor needs further investigation.
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Diferenciación Celular/fisiología , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/metabolismo , Endometrio/metabolismo , Transducción de Señal/fisiología , Células del Estroma/metabolismo , Ciclo Celular/fisiología , Ciclina D1/genética , Ciclina D1/metabolismo , Quinasa 2 Dependiente de la Ciclina/genética , Quinasa 2 Dependiente de la Ciclina/metabolismo , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/genética , Decidua/citología , Decidua/metabolismo , Endometrio/citología , Femenino , Genes cdc , Humanos , Interferencia de ARN , Células del Estroma/citologíaRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a recognized trigger factor for heart failure with preserved ejection fraction (HFpEF). Recent studies show that higher serum calcium level is associated with greater risk of both T2DM and heart failure. We speculate that increased serum calcium is related to HFpEF prevalence in patients with T2DM. METHODS: In this cross-sectional echocardiographic study, 807 normocalcemia and normophosphatemia patients with T2DM participated, of whom 106 had HFpEF. Multinomial logistic regression was carried out to determine the variables associated with HFpEF. The associations between serum calcium and metabolic parameters, as well as the rate of HFpEF were examined using bivariate linear correlation and binary logistic regression, respectively. The predictive performance of serum calcium for HFpEF was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: Patients with HFpEF have significantly higher serum calcium than those without HFpEF. Serum calcium was positively associated with total cholesterol, triglycerides, low-density lipoprotein cholesterol, serum uric acid, HOMA-IR and fasting plasma glucose. Compared with patients in the lowest serum calcium quartile, the odds ratio (OR) for HFpEF in patients in the highest quartile was 2.331 (95 % CI 1.088-4.994, p = 0.029). When calcium was analyzed as a continuous variable, per 1 mg/dL increase, the OR (95 % CI) for HFpEF was [2.712 (1.471-5.002), p = 0.001]. Serum calcium can predict HFpEF [AUC = 0.673, 95 % CI (0.620-0.726), p < 0.001]. CONCLUSIONS: An increase in serum calcium level is associated with an increased risk of HFpEF in patients with T2DM.
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Calcio/sangre , Diabetes Mellitus Tipo 2/epidemiología , Insuficiencia Cardíaca/epidemiología , Volumen Sistólico , Función Ventricular Izquierda , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biomarcadores/sangre , Glucemia/análisis , China/epidemiología , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatología , Ecocardiografía Doppler , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Humanos , Resistencia a la Insulina , Modelos Lineales , Lípidos/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Prevalencia , Curva ROC , Factores de Riesgo , Regulación hacia Arriba , Ácido Úrico/sangreRESUMEN
In the research of xenon sampling and xenon measurements, the xenon breakthrough curve plays a significant role in the xenon concentrating dynamics. In order to improve the theoretical comprehension of the xenon concentrating procedure from the atmosphere, the method of the breakthrough curve combination for sampling techniques should be developed and investigated under pulse injection conditions. In this paper, we describe a xenon breakthrough curve in a carbon molecular sieve column, the combination curve method for five conditions is shown and debated in detail; the fitting curves and the prediction equations are derived in theory and verified by the designed experiments. As a consequence, the curves of the derived equations are in good agreement with the fitting curves by tested. The retention times of the xenon in the column are 61.2, 42.2 and 23.5 at the flow rate of 1200, 1600 and 2000 mL min(-1), respectively, but the breakthrough times are 51.4, 38.6 and 35.1 min.
RESUMEN
AIM: This study aimed to determine the effects of small-conductance Ca(2+)-activated K(+) (SK) channels in colonic relaxation and the regulation of SK channels by estrogen. METHODS: The contractile activity of muscle strips from male rats was estimated, and drugs including vehicle (DMSO), 17ß-estradiol (E2), or apamin (SK blocker) were added, respectively. In a further experiment, muscle strips were preincubated with apamin before exposure to E2. The levels of the SK2 and SK3 protein expression in the colonic smooth muscle cells (SMCs) were detected. SMCs were treated with ICI 182780 (estrogen receptor [ER] antagonist) plus E2, BSA-E2, PPT (ERα agonist), or DPN (ERß agonist). SK3 mRNA and protein expression levels were detected. RESULTS: The muscle strips responded to E2 with a decrease and to apamin with a transient increase in tension. Preincubation with apamin partially prevented E2-induced relaxation. Two SK channel subtypes, SK2 and SK3, were coexpressed with α-actin in colonic SMCs. The quantitative ratio of the SK transcriptional expression in colonic SMCs was SK3 > SK2. The SK3 expression was upregulated by E2, and was downregulated by ICI 182780, but was not influenced by BSA-E2. Furthermore, the effect of PPT on the expression of SK3 was almost the same as that of E2, while DPN did not influence the protein expression of SK3. CONCLUSION: These findings indicate that SK3 is involved in the E2-induced relaxing effect on rat colonic smooth muscle. Furthermore, E2 upregulates the expression of SK3 in rat SMCs, and that this effect is mediated via the ERα receptor.
Asunto(s)
Apamina/farmacología , Colon/efectos de los fármacos , Estradiol/farmacología , Estrógenos/farmacología , Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/metabolismo , Actinas/efectos de los fármacos , Actinas/genética , Animales , Carbacol/farmacología , Colon/citología , Colon/fisiología , Dimetilsulfóxido/farmacología , Estradiol/análogos & derivados , Antagonistas del Receptor de Estrógeno/farmacología , Estrógenos/agonistas , Fulvestrant , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso/fisiología , Miocitos del Músculo Liso/metabolismo , Vehículos Farmacéuticos/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Albúmina Sérica Bovina/farmacología , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/genética , Transcripción Genética , Regulación hacia ArribaRESUMEN
OBJECTIVE: To investigate the relationship between traditional bullying, cyberbullying and depression in adolescents, with the involvement frequency and different roles considered. METHODS: A stratified cluster sampling method was used to randomly select 5 726 middle school students in three cities of Anhui province in December 2013. Those students were surveyed by self-designed questionnaire of adolescent health-related behaviors in Anhui province. Self-reports on the general demographic information, physical, verbal, relational bullying and cyberbullying involvement and depression were collected. Additionally, the items assessing depression were based on Self-rating Depression Scale (SDS). The chi-square test used to compare prevalent rates of bullying involvement and depression in different groups of students with different demographic features. Multinomial logistic regressions were performed to explore the relationships between all four types of bullying and depression, after controlling confounders. RESULTS: We got a final effective sample of 5 726 student. The response rate was 99.4% in this study. Among 5 726 adolescents, the prevalence rates of bullying in the last two months were 23.4% (1 339/5 726) physically, 55.0% (3 147/5 726) verbally, 34.2% (1 958/5 726) socially, and 8.9% (512/5 726) electronically. The prevalence rate of depression was 64.8% (3 711/5 726). The detection rate was higher in participants who involved in physical, verbal, relational, and cyber bullying than those who not involved in bullying. After controlling the confounding factors, the different frequency and role of verbal and relational bullying were risk factors of depression (OR = 1.42-3.71, all P values < 0.001). As for physical bullying, except for occasional bully-victims (OR = 1.08, 95% CI: 0.79-1.49), others were more likely to be depressed than noninvolved students. (OR = 1.40-7.84, all P values < 0.001). Frequent involvement in cyberbullying as bullies and (or) victims were more likely to be depressed than noninvolved students (OR = 2.30-4.55, all P values < 0.001), but occasional involvement in cyberbullying as bullies and (or) victims were not the risk factors of adolescents' depression (OR = 1.39, 95% CI:0.97-1.99; OR = 1.58, 95% CI: 0.88-2.82; OR = 1.50, 95% CI:0.82-2.74). CONCLUSION: Involvement in physical, verbal, relational, and cyberbullying were risk factors for depression among adolescent students.