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关键词： Endocannabinoids   Cannabinoid system   Granulosa cells   Fertility   Folliculogenesis   Apoptosis  

摘要： The endocannabinoid system (ECS) plays a crucial role in human reproduction. Changes in anandamide (AEA) levels affect reproductive events and has already been suggested as biomarker of reproductive potential of male and female gametes. Although cannabinoid-receptor 1 (CB1) was already identified in human granulosa cells (hGCs) the ECS was not characterized on granulosa cells line COV434 nor the effects of AEA on GCs viability and function depicted. Therefore, the aim of this study was to characterize the ECS elements and explore the effects of AEA on both COV434 and hGCs. Our results revealed that hGCs express the full enzymatic machinery responsible for AEA metabolism as well as cannabinoid receptors. In addition, AEA induced a reduction in both COV434 and hGCs viability in a concentration and time-dependent manner. Nevertheless, the effects of AEA in cell viability was independent of either CB1 or CB2 receptors. There was no ROS release in both cell models;however, AEA induced morphological changes, presenting chromatin condensation at 72 h, and variation on mitochondrial membrane potential. Moreover, AEA induced an increase in caspase-3/-7 activities in both cell models, but in hGCs there was also an increase in caspase 8 activity. This study supports the idea that ECS balance is crucial for folliculogenesis and oocyte quality as dysregulated AEA levels may compromise female fertility.

摘要： Objectives: Despite recent advances in adjuvant therapy for various gynecologic malignancies, the prognosis of patients presenting with stage IVB uterine serous carcinoma (USC) remains extremely poor, with a reported 5-year survival of <20%. The goal of this study is to evaluate the survival impact of cytoreductive surgery and identify other prognostic factors in stage IVB USC. Methods: A multicenter retrospective analysis of patients with stage IVB USC was conducted from 2000 - 2018. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking; followed by adjuvant chemotherapy±external beam radiation therapy (EBRT). Optimal cytoreduction (R1) was defined as residual disease <=1 cm at completion of surgery, and suboptimal cytoreduction (R2) was defined as >=1cm. Patients receiving neoadjuvant chemotherapy were excluded from analysis. Progression free survival (PFS) and overall survival (OS) analysis was performed using Kaplan-Meier estimates. Multivariate analysis (MVA) was performed using Cox proportional hazards model. Results: Final analysis included 68 patients. 50 (74%) patients were cytoreduced to R1 and 18 (26%) to R2. Additionally, 11 (16%) R1 patients were cytoreduced to no gross residual disease (R0). The mean age was 66 years (range 44-89) and 96% of patients were African American. The majority of patients, 56 (82%), received systemic chemotherapy alone and 12 (18%) received a combination of chemotherapy and EBRT±vaginal brachytherapy (chemoradiation). Adjuvant therapy regimens were well-balanced between R1 and R2 patients (p =0.992). There was no difference in the frequency of treatment delays between regimens (p =0.832). 96% of patients received platinum-based chemotherapy. There was no difference in the age (p =0.227), race (p =0.936), type of radiotherapy (p =0.852) or chemotherapy regimen received (p =0.996) between R1 and R2 cohorts. The median PFS for all patients was 8 months and the median OS was 13 months. C

关键词： Prebiotics   Crohn's disease   Microbiota   Pre-disease   First-degree relative   Prevention  

摘要： Background & aims: Siblings of people with Crohn's disease (CD) share aspects of the disease phenotype (raised faecal calprotectin, altered microbiota), which are markers of risk for their own development of CD. The aim was to determine whether supplementation with prebiotic oligofructose/inulin induces a prebiotic response and impacts the risk phenotype in CD patients and siblings. Methods: Patients with inactive CD (n = 19, CD activity index <150) and 12 of their unaffected siblings (with calprotectin >50 mg/g) ingested oligofructose/inulin (15 g/day) for three weeks. Faecal microbiota (qPCR), intestinal permeability (lactulose-rhamnose test), blood T cells (flow-cytometry) and calprotectin (ELISA) were measured at baseline and follow-up. Results: Following oligofructose/inulin, calprotectin did not significantly change in patients (baseline mean 537 SD 535 mg/g;follow-up mean 974 SD 1318 mg/g, p = 0.08) or siblings (baseline mean 73 SD 90 mg/g: follow up mean 58 SD 72 mg/g, p = 0.62). Faecal Bifidobacteria and Bifidobacterium longum increased in patients and siblings;Bifidobacterium adolescentis and Roseburia spp. increased only in siblings. Compared with patients, siblings had a greater magnitude change in Bifidobacteria (+14.6% vs +0.4%, p = 0.028), B. adolescentis (+1.1% vs 0.0% p = 0.006) and Roseburia spp. (+1.5% vs -0.1% p = 0.004). Intestinal permeability decreased significantly in patients after oligofructose/inulin to a level that was similar to siblings. Blood T cell abundance reduced in siblings but not patients following oligofructose/inulin. Conclusions: Oligofructose/inulin supplementation did not significantly impact calprotectin, but the prebiotic effect was more marked in healthy siblings compared with patients with inactive CD and was associated with alterations in other CD risk markers. Future research should focus on dietary intervention, including with prebiotics, in the primary prevention of CD. (c) 2021 Elsevier Ltd and European Society for

关键词： Large-eddy simulation (LES)   Facade geometrical details   Wind speed   Pressure coefficient   Balcony geometry   High-rise building  

摘要： The presence of building balconies can significantly modify the near-facade wind flow pattern and surface pressures. The present study evaluates the impact of building balcony geometry on mean wind speed on balcony spaces and wind-induced mean surface pressure for generic high-rise buildings. The focus is on balconies that extend along the entire width of the building facade. Large-eddy simulations (LES), validated with wind tunnel experiments, are conducted to investigate the impact of (i) balconies present or not, (ii) balcony depth, (iii) balcony parapet walls, (iv) balcony partition walls, and (v) density of balconies. The results indicate that the balcony geometry can greatly affect the mean wind speed on balcony spaces and the local and facade-averaged mean pressure coefficient (Cp). The presence of balconies can increase the facade-averaged Cp over the windward and leeward facades by 5.2% and 8.9%, respectively. These numbers rise to 23.5% and 23.3% when two partition walls are added at the lateral edges of the facades. Adding five partition walls can reduce the overall areaaveraged wind speed on balcony spaces by 68.0% compared to the case without partition walls. These findings can be useful in developing, designing and constructing buildings with facade geometrical details that improve building ventilation, air quality and wind comfort.

关键词： Vascular smooth muscle cells   Primary cell culture   RVSMCs   Phenotype  

摘要： An efficient and simple method to obtain aortic media for primary culture of rat vascular smooth muscle cells (RVSMCs) is developed. The main steps to obtain aortic media include isolation of rat aortic artery, removal of the fat tissue and branches, separation of longitudinal cutting edge, and peeling off the adventitia. Then, aortic media was used to obtain RVSMCs by our tissue explants method and the enzyme digestion method. The removal efficiency of the intima and adventitia was confirmed by hematoxylin-eosin and immunohistochemical staining. Morphology and immunofluorescent staining were used to identify cells and cell purity. RVSMCs at the 3rd and 8th passages were isolated by our tissue explants method;the enzyme digestion method and the traditional tissue explants method were compared respectively. Western blotting and gel contraction assay were used to investigate the phenotype and contraction ability of RVSMCs obtained by the different methods. Compared with the other methods, RVSMCs isolated by our method showed higher purity and demonstrated "contractile" phenotype with retained contraction ability for more passages. And the aortic media obtained showed no visible damage with few endothelial cells and fibroblasts remained. An efficient and simple method was established to obtain rat aortic media for primary culture of RVSMCs with high purity, "contractile" phenotype characteristics, and more stable during subculturing.

关键词： CRISPR   Cas9   Kaposi&apos   s sarcoma   KSHV   Loss of episome   Primary effusion lymphoma   Reversion of cellular transformation   Viral latent protein LANA  

摘要： Viral infection has been implicated in the pathogenesis of a plethora of human diseases. Although antiviral therapies effectively confront the viral spread and infection, how to completely eradicate the viral genome from infected cells remains a challenge. In this study, we demonstrated the reversible switching of primary cells between normal and malignant states by an oncogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) and CRISPR/Cas9-mediated targeting of a major viral latent protein. Primary cells can be transformed into malignant status by infection of KSHV, while elimination of the KSHV genome from latent KSHV-infected cells reverses KSHV-transformed primary cells back to a "normal state" by CRISPR/Cas-mediated knockout of viral major latent gene LANA. As a proof of concept, we demonstrated efficient elimination of KSHV episome in KSHV-associated primary effusion lymphoma cells resulting in the induction of apoptosis by liposome-encapsulated CRISPR/Cas9 ribonucleoprotein complexes (Lipo/Cas9-LANAsgRNA). Our work illustrates CRISPR/Cas as a promising technology for eliminating oncogenic viruses from persistently infected cells by taking advantage of the genetic differences between viral and cellular genomes. Compared to traditional antiviral therapy, our study offer an approach for antagonizing human oncogenic virus-related cancers by directly targeting as well as clearing viral genomes.

摘要： Highlights•PMLBCL rarely extends to extranodal subdiaphragmatic (ES) sites at diagnosis. •Among 455 patients, 32 (7%) had such localization at baseline. •Kidney, liver, and adrenals were most frequently involved. •ES site involvement had not independent prognostic impact beyond that of stage IV.

关键词： CNS relapse   immunotherapy   pembrolizumab   primary mediastinal lymphoma  

摘要： Primary mediastinal large B-cell lymphoma (PMBCL) is a rare aggressive B-cell lymphoma characterized by the frequent presence of amplification and translocation events at 9p24.1, resulting in the expression of the programmed cell death-1 (PD-1) ligands PD-L1 and PD-L2. Pembrolizumab, a humanized anti-PD-1 monoclonal antibody, binds PD-1 and blocks this interaction, enhancing the activity of the immune system against tumor cells, and has shown activity in PMBCL and in some cases of primary and secondary central nervous system (CNS) lymphoma. We report the case of a 40-year-old woman diagnosed with relapsed PMBCL and secondary CNS involvement who responded to pembrolizumab monotherapy, allowing for a later allogeneic stem cell transplant.

关键词： Wheat kernels   Spectrogram   SPGAN-PNAS   Classification  

摘要： Quantity and quality of grain are both closely related to national development and social stability. Grain is lost during storage due to mildew and insects. Detection of damaged grain kernels not only can reduce the loss of grain, but also protect human beings from diseases caused by damaged grain. Therefore, research on the automatic detection of damaged grain is of continued urgency. In this paper, we propose a framework combining spectrogram generative adversarial network and progressive neural architecture search (SPGAN-PNAS) to detect and classify mildew-damaged wheat kernels (MDK), insect damaged wheat kernels (IDK) and undamaged wheat kernels (UDK). First, the spectrogram generative adversarial network (SPGAN) is designed to enlarge the data set. Second, we apply progressive neural architecture search (PNAS) to generate network structure to classify three types of wheat kernels. An F1 of 96.2% is obtained using the proposed method with 5-fold cross-validation. The results are superior to the classical neural networks for detection and classification of damaged wheat kernels. Experimental results show that the structure of SPGAN-PNAS is feasible and effective. (c) 2021 IAgrE. Published by Elsevier Ltd. All rights reserved.