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BackgroundNOS1 expression predicts poor prognosis in patients with melanoma. However, the molecular function of NOS1 in the type I IFN response and immune escape of melanoma is still unknown.MethodsThe CRISPR/Cas9 system was used to generate NOS1-knockout melanoma cells and the biological characteristics of NOS1-knockout cells were evaluated by MTT assay, clonogenic assay, EdU assay, and flow cytometric assay. The effect on tumor growth was tested in BALB/c-nu and C57BL/6 mouse models. The gene expression profiles were detected with Affymetrix microarray and RNA-seq and KEGG (Kyoto Encyclopedia of Genes and Genomes) and CLUE GO analysis was done. The clinical data and transcriptional profiles of melanoma patients from the public database TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus, GSE32611) were analyzed by Qlucore Omics Explorer.ResultsNOS1 deletion suppressed the proliferation of melanoma A375 cells in culture, blocked cell cycling at the G0/G1 phase, and decreased the tumor growth in lung metastasis nodes in a B16 melanoma xenograft mouse model. Moreover, NOS1 knockout increased the infiltration of CD3+ immune cells in tumors. The transcriptomics analysis identified 2203 differential expression genes (DEGs) after NOS1 deletion. These DEGs indicated that NOS1 deletion downregulated mostly metabolic functions but upregulated immune response pathways. After inhibiting with NOS1 inhibitor N-PLA, melanoma cells significantly increased the response to IFN[Formula: see text] by upregulation expression of IFN[Formula: see text] simulation genes (ISGs), especially the components in innate immune signaling, JAK-STAT, and TOLL-LIKE pathway. Furthermore, these NOS1-regulating immune genes (NOS1-ISGs) worked as a signature to predict poor overall survival and lower response to chemotherapy in melanoma patients.ConclusionThese findings provided a transcriptional evidence of NOS1 promotion on tumor growth, which is correlated with metabolic regulation and immune escape in melanoma cells.

One of the malignant transformation hallmarks is metabolism reprogramming, which plays a critical role in the biosynthetic needs of unchecked proliferation, abrogating cell death programs, and immunologic escape. However, the mechanism of the metabolic switch is not fully understood. Here, we found that the S-nitrosoproteomic profile of endogenous nitrogen oxide in ovarian cancer cells targeted multiple components in metabolism processes. Phosphofructokinase (PFKM), one of the most important regulatory enzymes of glycolysis, was S-nitrosylated by nitric oxide synthase NOS1 at Cys351. S-nitrosylation at Cys351 stabilized the tetramer of PFKM, leading to resist negative feedback of downstream metabolic intermediates. The PFKM-C351S mutation decreased the proliferation rate of cultured cancer cells, and reduced tumor growth and metastasis in the mouse xenograft model. These findings indicated that S-nitrosylation at Cys351 of PFKM by NOS1 contributes to the metabolic reprogramming of ovarian cancer cells, highlighting a critical role of endogenous nitrogen oxide on metabolism regulations in tumor progression.

Aiming at the problem of target allocation in operations of special-shaped anti-ship missile swarms, a target allocation model based on time coordination is established. Firstly, according to the anti-ship combat situation information, the influence of missile flight time, missile-to-target distance and flight velocity on the target allocation of cluster coordination operations is analyzed, and a time coordination advantage function based on the standard deviation of missile flight time is established, and the comprehensive advantage function is formed integrated the distance advantage function with velocity advantage function. Finally, the optimal solution of model is deduced by genetic algorithm, and the allocation results are gotten by simulation. The results of comparative analysis show that the standard deviation of average time of operation scheme with time coordination is lower than that without time coordination. The standard deviation of average time for two cases descends about 49.18% and 63.49%. The simulation results verify the validity of the model.

As the penetration of renewable energy sources (RESs) in power systems continues to increase, their volatility and unpredictability have exacerbated the burden of frequency regulation (FR) on conventional generator units (CGUs). Therefore, to reduce frequency deviations caused by comprehensive disturbances and improve system frequency stability, this paper proposes an integrated strategy for hybrid energy storage systems (HESSs) to participate in primary frequency regulation (PFR) of the regional power grid. Once the power grid frequency exceeds the deadband (DB) of the HESS, the high-frequency signs of the power grid frequency are managed by the battery energy storage system (BESS) through a division strategy, while the remaining parts are allocated to pumped hydroelectric energy storage (PHES). By incorporating positive and negative virtual inertia control and adaptive droop control, the BESS effectively maintains its state of charge (SOC), reduces the steady-state frequency deviation of the system, and provides rapid frequency support. When the system frequency lies within the DB of the HESS, an SOC self-recovery strategy restores the BESS SOC to an ideal range, further enhancing its long-term frequency regulation (FR) capability. Finally, a regional power grid FR model is established in the RT-1000 real-time simulation system. Simulation validation is conducted under three scenarios: step disturbances, short-term continuous disturbances, and long-term RES disturbances. The results show that the proposed integrated strategy for HESS participation in PFR not only significantly improves system frequency stability but also enhances the FR capability of the BESS. [ABSTRACT FROM AUTHOR]

The notions of os{o}_{s}-convergence and S∗{S}^{\ast }-doubly quasicontinuous posets are introduced, which can be viewed as common generalizations of Birkhoff’s order-convergence and S∗{S}^{\ast }-doubly continuous posets, respectively. We first consider the relationship between os{o}_{s}-convergence and B-topology and show that the topology induced by os{o}_{s}-convergence according to the standard topological approach is the B-topology precisely. Then, the topological characterization for the S∗{S}^{\ast }-doubly quasicontinuity is presented. It is proved that a poset is S∗{S}^{\ast }-doubly quasicontinuous iff the poset equipped with the B-topology is locally hyperclosed iff the lattice of all B-open subsets of the poset is hypercontinuous. Finally, the order theoretical condition for the os{o}_{s}-convergence being topological is given and the complete regularity of B-topology on S∗{S}^{\ast }-doubly quasicontinuous posets is explored.

In this paper, the α waybelow relation, which is determined by O2-convergence, is characterized by the order on a poset, and a sufficient and necessary condition for O2-convergence to be topological is obtained.