Identification of a novel microRNA-mRNA regulatory biomodule in human prostate cancer

Our recent study identified a list of differentially expressed microRNAs (miRNAs) in human prostate cancer (PCa) tissues compared to adjacent benign prostate tissues. In the current study, to identify the crucial miRNA–mRNA regulatory biomodule involved into prostate carcinogenesis based on the previous miRNA expression profile in PCa, we proposed an integrated systematic approach which combined miRNA-mediated gene expression regulatory network analysis, experimental validations in vitro and in vivo, as well as clinical significance evaluation. As a result, the CCND1-RNASEL-CDKN1A-TP73-MDM2-UBE2I axis was identified as a bottleneck in the miRNA-mediated gene expression regulatory network of PCa according to network topological analysis. The direct binding relationship between TP73 and PCa downregulated miR-193a-5p, and the direct binding relationship between UBE2I and PCa upregulated miR-188-5p were both experimentally validated. In addition, miR-193a-5p had a more significant regulatory effect on the tumor promoter isoform of TP73-deltaNp73 than on the tumor suppressive isoform of TP73-TAp73. Importantly, the deregulation of either the miR-193a-5p-TP73 or miR-188-5p-UBE2I axes was significantly associated with aggressive progression and poor prognosis in PCa patients. Gain- and loss-of-function experiments showed that miR-193a-5p efficiently inhibited in vitro PCa cell proliferation, migration, and invasion, and in vivo tumor growth, and markedly induced PCa cell apoptosis via regulating TP73 with a corresponding suppression of the CCND1-RNASEL-CDKN1A-MDM2 axis. In contrast, miR-188-5p exerted its tumor promoter roles through targeting UBE2I with a subsequent activation of the CCND1-RNASEL-CDKN1A-MDM2 axis. Taken together, this integrated analysis revealed the potential roles of the miR-193a-5p/TP73 and miR-188-5p/UBE2i negative regulation pairs in PCa. In addition to the significant clinical relevance, miR-193a-5p- and miR-188-5p-regulated CCND1-RNASEL-CDKN1A-TP73-MDM2-UBE2I signaling may be a novel regulatory biomodule in prostate carcinogenesis

Saltwater intrusion into the Changjiang River : a model-guided mechanism study

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 114 (2009): C02006, doi:10.1029/2008JC004831.The Changjiang River (CR) is divided into a southern branch (SB) and a northern branche (NB) by Chongming Island as the river enters the East China Sea. Observations reveal that during the dry season the saltwater in the inner shelf of the East China Sea flows into the CR through the NB and forms an isolated mass of saltwater in the upstream area of the SB. The physical mechanism causing this saltwater intrusion has been studied using the high-resolution unstructured-grid Finite-Volume Coastal Ocean Model (FVCOM). The results suggest that the intrusion is caused by a complex nonlinear interaction process in relation to the freshwater flux upstream, tidal currents, mixing, wind, and the salt distribution in the inner shelf of the East China Sea. The tidal rectification, resulting from the interaction of the convergence or divergence of tidal momentum flux and bottom friction over abrupt topography, produces a net upstreamward volume flux from NB to SB. With river discharge the net water transport in the NB is driven through a momentum balance of surface elevation gradient forcing, horizontal advection, and vertical diffusion. In the dry season, reducing the surface elevation gradient forcing makes tidal rectification a key process favorable for the saltwater intrusion. A northerly wind tends to enhance the saltwater intrusion by reducing the seaward surface elevation gradient forcing rather than either the baroclinic pressure gradient forcing or the wind-driven Ekman transport. A convergence experiment suggests that high grid resolution (∼100 m or less) is required to correctly resolve the net water transport through the NB, particularly in the narrow channel on the northern coast of Chongming Island.The development of FVCOM is supported by the Massachusetts Fisheries Institute through NOAA grants DOC/ NOAA/NA04NMF4720332 and DOC/NOAA/NA05NMF4721131; NSF grants OCE-0234545, OCE-0227679, OCE-0606928, OCE-0712903, OCE-0732084, OCE-0726851, ARC0712903; ARC0732084, and ARC0804029; NOAA grant NA160P2323; and an ONR subcontract grant from the Woods Hole Oceanographic Institution. The development of the nested modeling approach is supported by MIT and URI Sea Grant projects NA060AR41700019 and R/P-061. C. Chen serves as Zi Jiang Scholar at the State Key Laboratory for Estuarine and Coastal Research, East China Normal University (ECNU), and is an adjunct professor at Shanghai Ocean University (SHOU). His contribution is also supported by both ECNU and SHOU. P. Ding is supported by the Chinese National Key Basic Research Project grant 2002CB412403

A reactive oxygen species–related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is a malignant disease containing tumor-infiltrating lymphocytes. Reactive oxygen species (ROS) are present in the tumor microenvironment and are strongly associated with cancer development. Nevertheless, the role of ROS-related genes in ccRCC remains unclear.MethodsWe describe the expression patterns of ROS-related genes in ccRCC from The Cancer Genome Atlas and their alterations in genetics and transcription. An ROS-related gene signature was constructed and verified in three datasets and immunohistochemical staining (IHC) analysis. The immune characteristics of the two risk groups divided by the signature were clarified. The sensitivity to immunotherapy and targeted therapy was investigated.ResultsOur signature was constructed on the basis of glutamate-cysteine ligase modifier subunit (GCLM), interaction protein for cytohesin exchange factors 1 (ICEF1), methionine sulfoxide reductase A (MsrA), and strawberry notch homolog 2 (SBNO2) genes. More importantly, protein expression levels of GCLM, MsrA, and SBNO2 were detected by IHC in our own ccRCC samples. The high-risk group of patients with ccRCC suffered lower overall survival rates. As an independent predictor of prognosis, our signature exhibited a strong association with clinicopathological features. An accurate nomogram for improving the clinical applicability of our signature was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the signature was closely related to immune response, immune activation, and immune pathways. The comprehensive results revealed that the high-risk group was associated with high infiltration of regulatory T cells and CD8+ T cells and more benefited from targeted therapy. In addition, immunotherapy had better therapeutic effects in the high-risk group.ConclusionOur signature paved the way for assessing prognosis and developing more effective strategies of immunotherapy and targeted therapy in ccRCC

Ongoing Conflict Makes Yemen Dark: From the Perspective of Nighttime Light

The Yemen conflict has caused a severe humanitarian crisis. This study aims to evaluate the Yemen crisis by making use of time series nighttime light images from the Suomi National Polar-Orbiting Partnership Visible Infrared Imaging Radiometer Suite sensor (NPP-VIIRS). We develop a process flow to correct NPP-VIIRS nighttime light from April 2012 to March 2017 by employing the Defense Meteorological Satellite Program Operational Linescan System (DMSP-OLS) stable nighttime light image. The time series analyses at national scales show that there is a sharp decline in the study period from February 2015 to June 2015 and that the total nighttime light (TNL) of Yemen decreased by 71.60% in response to the decline period. The nighttime light in all provinces also showed the same decline period, which indicates that the Saudi-led airstrikes caused widespread and severe humanitarian crisis in Yemen. Spatial pattern analysis shows that the areas of declining nighttime light are mainly concentrated in Sana’a, Dhamar, Ibb, Ta’izz, ’Adan, Shabwah and Hadramawt. According to the validation with high-resolution images, the decline in nighttime light in Western cities is caused by the damage of urban infrastructure, including airports and construction; moreover, the reason for the decline in nighttime light in eastern cities is the decrease in oil exploration. Using nighttime light remote sensing imagery, our findings suggest that war made Yemen dark and provide support for international humanitarian assistance organizations

Ki-67 and PCNA expression in prostate cancer and benign prostatic hyperplasia

Objective: Ki-67 is a proliferation-associated nuclear antigen and is expressed in all cycling cells except for resting cells in the G0-phase. PCNA is an acidic nuclear protein and has been recognized as a histologic marker for the G1/S phase in the cell cycle. Ki-67and PCNA labeling indices are considered to reflect cell proliferation, particularly, growth fraction. The purpose of this study is to investigate the expression levels of Ki-67 and PCNA in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their potential on the early diagnosis of PCa. Methods: Human prostate cancer cell lines LNCaP and PC-3, human normal prostate epithelial cell line HuPEC, tissues from patients with PCa (121 cases) and BPH (45) and 36 normal cases were examined for the expression of Ki-67 and PCNA by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Then, the association of Ki-67 and PCNA expression with clinical grading of PCa was analyzed by immunohistochemistry staining. Results: The ratios of PCNA and Ki-67 expression levels in LNCaP and PC-3 were higher (P < 0.05, P < 0.001) than that in HuPEC. The two markers were differentially expressed in three tissues and showed increased expression in PCa (P < 0.05) and BPH (P < 0.05), relative to human normal prostate tissues. Compared with BPH, the ratio of Ki-67 and PCNA expressed in tumour tissue was increased (P < 0.05). The increase of Ki-67 was greater than that of PCNA. Expression of the two markers increased after different grading of PCa cases. The values of Ki-67/PCNA were: 0.073 in grade I PCa tissues, 0.119 in grade IIa PCa tissues, 0.141 in grade IIa PCa tissues, 0.234 in grade III PCa tissues. Conclusion: The combination of Ki-67 and PCNA, specific proliferative markers of PCa, may improve the accuracy of early diagnosis of prostatic cancer

Stiffness-Performance-Based Redundant Motion Planning of a Hybrid Machining Robot

Large-scale components usually have complex structures with high local stiffness, and the holes on them are required to be machined with high precision, which makes it important and challenging to study how to efficiently and precisely drill in the large-scale components. This article presents mobile hybrid machining equipment that consists of a five-axis parallel module, a 2-degree-of-freedom (DoF) robotic, arm and an automated guide vehicle (AGV) connected in series. With the ability of wide-range positioning and precise local processing, it has potential advantages in the drilling processing of large-scale components. Stiffness is one of the most important performances for machining equipment, and it’s highly related to the its configuration. For the discussed equipment, the stiffness is determined by the two-stage-positioning hybrid machining robot, which comprises a five-axis parallel module and a two-DoF robotic arm. The redundant motion of the hybrid machining robot makes it possible to optimize its configuration by reasonably planning redundant motion. Therefore, a redundant motion-planning method based on stiffness performance is proposed. A kinematic analysis of the five-axis parallel module, the robotic arm, and the hybrid machining robot is carried out. A hybrid robot usually consists of several subsystems, and to take the compliance of each subsystem into consideration, the stiffness-modeling method for the hybrid robot with n subsystems connected in series is proposed. The stiffness model of the hybrid machining robot is established by using this method, and the variation of the stiffness magnitude has the same trend as that obtained by using FEA software. Stiffness magnitude and isotropy indices are proposed to evaluate the robot’s stiffness performance along the axis of the spindle and in the plane perpendicular to the axis of the spindle. The redundant motion of the hybrid machining robot is planned by maximizing the stiffness magnitude along the spindle axis, with priority to the stiffness isotropy index. Finally, the drilling experiment is carried out, and the results show that the relative error of the hole diameter obtained under the optimal configuration of the hybrid machining robot is 1.63%, which is smaller than those obtained under the other two configurations for comparison with relative errors of 3.75% and 3.50%, respectively. It proves the validity of the redundant motion-planning method. The proposed stiffness-modeling method and the stiffness-performance indices are also applicable to other hybrid machining robots

Protective effect of glycyrrhizin on nephrotic syndrome induced by adriamycin in rats

Purpose: To explore the protective effect of glycyrrhizin in rats with nephrotic syndrome (NS) induced by adriamycin (ADR). Methods: 36 Sprague Dawley (SD) male rats were divided into control, untreated and glycyrrhizin treatment groups. The NS rat model was established by injecting ADR twice in the untreated and in the glycyrrhizin treatment groups. Rats in the glycyrrhizin treatment group were fed glycyrrhizin by intragastric administration for 7 days. Changes in the following indices were observed in the three groups before and 4 weeks after the treatment: 24h urine protein quantitation (UPr), serum cholesterol (Ch), serum albumin (Alb), blood urea nitrogen (BUN), serum creatinine (sCr), laminin (LN), fibronectin (FN), collagen (Col), transforming growth factor ?1 (TGF?1) and connective tissue growth factor (CTGF); histopathology by light and electron microscope. Expression of LN, FN, Col?, TGF?1 and CTGF in the cortex of the kidney were detected by semi-quantitive immunohistochemical analysis. Expression of TGF?1 and CTGF in the cortex of the kidney was detected by Fluorescein Based Quantitive RT-PCR. Macrophage infiltration was evaluated by the immunoperoxidase staining. Results: Compared with the control group, 24h UPr, Ch, BUN and sCr of rats in the untreated group were increased. Glycyrrhizin reduced 24h Upr, Ch, BUN, sCr, LN, FN, Col, TGF?1, CTGF, and mean arterial blood pressure. Pathological changes in the kidney, the expression of LN, FN, Col, TGF?1 and CTGF in the cortex of the kidney in the glycyrrhizin treatment group were decreased compared with the untreated group. Glycyrrhizin also suppressed macrophage infiltration in the kidneys of NS rat models. Conclusion: Glycyrrhizin exerts protective effects in rats with NS, reducing the excretion of Upr, Ch, BUN, sCr, and mean arterial blood pressure, and also decreasing expression of LN, FN, Col, TGF?1 and CTGF in the kidney. Renal function is improved and the severity of NS is lessened

Landslide spatial modelling using novel bivariate statistical based Naïve Bayes, RBF Classifier, and RBF network machine learning algorithms

Landslides are major hazards for human activities often causing great damage to human lives and infrastructure. Therefore, the main aim of the present study is to evaluate and compare three machine learning algorithms (MLAs) including Naïve Bayes (NB), radial basis function (RBF) Classifier, and RBF Network for landslide susceptibility mapping (LSM) at Longhai area in China. A total of 14 landslide conditioning factors were obtained from various data sources, then the frequency ratio (FR) and support vector machine (SVM) methods were used for the correlation and selection the most important factors for modelling process, respectively. Subsequently, the resulting three models were validated and compared using some statistical metrics including area under the receiver operating characteristics (AUROC) curve, and Friedman and Wilcoxon signed-rank tests The results indicated that the RBF Classifier model had the highest goodness-of-fit and performance based on the training and validation datasets. The results concluded that the RBF Classifier model outperformed and outclassed (AUROC = 0.881), the NB (AUROC = 0.872) and the RBF Network (AUROC = 0.854) models. The obtained results pointed out that the RBF Classifier model is a promising method for spatial prediction of landslide over the world