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This study aimed to determine the main active ingredients of the Ginseng-Gegen (Panax Ginseng-Radix Puerariae) drug pair, to predict relevant action targets, and to establish a network of "drug-active ingredients-targets", to ultimately explore the mechanism of Ginseng-Gegen in the treatment of mesenteric lymphadenitis.The Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform was used to screen the chemical constituents of Ginseng-Gegen, and the active ingredient targets were retrieved by UniProt database. The databases of GeneCards and the Online Mendelian Inheritance in Man (OMIM) were applied to search for mesenteric lymphadenitis-related targets. Cytoscape software was used to construct the network of active ingredient-action targets. The biological functions of the targets were analyzed in the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database.A total of 26 potential active ingredients of the Ginseng-Gegen drug pair were screened, with 128 drug-related targets and 255 mesenteric lymphadenitis-related targets. After matching, 23 potential targets were obtained for treating mesenteric lymphadenitis. Among them,Ginseng-Gegen is related to oxidative stress and inflammation, and it is a part of the nuclear factor κB (NF-κB) signaling pathway, tumor necrosis factor (TNF) signaling pathway, and the advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) signaling pathway. These biological processes and signaling pathways may be potential mechanisms of Ginseng-Gegen for treating mesenteric lymphadenitis.

MicroRNAs (miRNAs) regulate multiple biological processes and participate in various cardiovascular diseases. This study aims to investigate the role of miR-339-5p in cardiomyocyte hypertrophy and the involved mechanism. Neonatal rat cardiomyocytes (NRCMs) were cultured and stimulated with isoproterenol (ISO). The hypertrophic responses were monitored by measuring the cell surface area and expression of hypertrophic markers including β-myosin heavy chain (β-MHC) and atrial natriuretic factor (ANF). Bioinformatic prediction tools and dual-luciferase reporter assay were performed to identify the target gene of miR-339-5p. Quantitative real-time polymerase chain reaction and Western blot analysis were used to determine the levels of miR-339-5p and its downstream effectors. Our data showed that miR-339-5p was up-regulated during cardiomyocyte hypertrophy triggered by ISO. MiR-339-5p overexpression resulted in enlargement of cell size and increased the levels of hypertrophic markers. In contrast, inhibition of miR-339-5p significantly attenuated ISO-induced hypertrophic responses of NRCMs. Valosin-containing protein (VCP), a suppressor of cardiac hypertrophy via inhibiting mechanistic target of rapamycin (mTOR) signaling, was validated as a target of miR-339-5p. MiR-339-5p suppressed VCP protein expression, leading to elevated phosphorylation of mTOR and ribosomal protein S6 kinase (S6K). VCP depletion activated the mTOR/S6K cascade and could compromise the anti-hypertrophic effects of miR-339-5p inhibitor. Additionally, the hypertrophic responses caused by miR-339-5p was alleviated in the presence of mTOR inhibitor rapamycin. In conclusion, our research revealed that miR-339-5p promoted ISO-induced cardiomyocyte hypertrophy by targeting VCP to activate the mTOR signaling, suggesting a promising therapeutic intervention by interfering miR-339-5p. This article is protected by copyright. All rights reserved.

Although bottom-up attention can improve visual performance with and without awareness to the exogenous cue, whether they are governed by a common neural computation remains unclear. Using a modified Posner paradigm with backward masking, we found that the cueing effect displayed a monotonic gradient profile (Gaussian-like), both with and without awareness, whose scope, however, was significantly wider with than without awareness. This awareness-dependent scope offered us a unique opportunity to change the relative size of the attention field to the stimulus, differentially modulating the gain of attentional selection, as proposed by the normalization model of attention. Therefore, for each human subject (male and female), the stimulus size was manipulated as their respective mean attention fields with and without awareness while stimulus contrast was varied in a spatial cueing task. By measuring the gain pattern of contrast-response functions on the spatial cueing effect derived by visible or invisible cues, we observed changes in the cueing effect consonant with changes in contrast gain for visible cues and response gain for invisible cues. Importantly, a complementary analysis confirmed that subjects' awareness-dependent attention fields can be simulated by using the normalization model of attention. Together, our findings indicate an awareness-dependent normalization framework of visual bottom-up attention, placing a necessary constraint, namely, awareness, on our understanding of the neural computations underlying visual attention.SIGNIFICANCE STATEMENTBottom-up attention is known to improve visual performance with and without awareness. We discovered that manipulating subjects' awareness can modulate their attention fields of visual bottom-up attention, which offers a unique opportunity to regulate its normalization processes. On the one hand, by measuring the gain pattern of contrast-response functions on the spatial cueing effect derived by visible or invisible cues, we observed changes in the cueing effect consonant with changes in contrast gain for visible cues and response gain for invisible cues. On the other hand, by using the normalization model of attention, subjects' awareness-dependent attention fields can be simulated successfully. Our study supports important predictions of the normalization model of visual bottom-up attention and further reveals its dependence on awareness.

Three-dimensional (3D) contrast-enhanced TTo compare 3D CE-TProspective.One hundred and seventy-five patients with brain tumors, 65 were male, 110 were female. Including histologically confirmed 73 meningiomas, 23 schwannomas, 20 gliomas, 7 hemangioblastomas, 5 metastases, 2 lymphomas, 2 hemangiopericytomas, 2 germ cell tumors, 1 craniopharyngioma, and 1 cholesteatoma.A 3-T, CE-TThree neuroradiologists counted the number of intratumoral vessels on CE-TTwo-way random intraclass correlation coeficient (ICC) was used for inter-reader agreement regarding intratumoral vessel and microbleed counts, and the linear regression analysis (with F-test) was used to study the correlation between intratumoral vessels and microbleeds based on CE-TInter-reader agreements for intratumoral vessel count on CE-TMore intratumoral vessels could potentially be identified using a 3D CE-T2 TECHNICAL EFFICACY: Stage 3.

In the electrical power system, the coordination of directional overcurrent protection relays (DOPR) plays a preeminent role in protecting the electrical power system with the help of primary and back up protection to keep the system vigorous and to avoid unnecessary interruption. The coordination between these relays should be pursued at optimal value to minimize the total operating time of all main relays. The coordination of directional overcurrent relay is a highly constrained optimization problem. The DOPR problem has been solved by using a hybridized version of particle swarm optimization (HPSO). The hybridization is achieved by introducing simulated annealing (SA) in original PSO to avoid being trapped in local optima and successfully searching for a global optimum solution. The HPSO has been successfully applied to five case studies. Furthermore, the obtained results outperform the other traditional and state of the art techniques in terms of minimizing the total operating of DOPR and convergence characteristics, and require less computational time to achieve the global optimum solution.