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Global optimization problems have been a research topic of great interest in various engineering applications among which neural network algorithm (NNA) is one of the most widely used methods. However, it is inevitable for neural network algorithms to plunge into poor local optima and convergence when tackling complex optimization problems. To overcome these problems, an improved neural network algorithm with quasi-oppositional-based and chaotic sine-cosine learning strategies is proposed, that speeds up convergence and avoids trapping in a local optimum. Firstly, quasi-oppositional-based learning facilitated the exploration and exploitation of the search space by the improved algorithm. Meanwhile, a new logistic chaotic sine-cosine learning strategy by integrating the logistic chaotic mapping and sine-cosine strategy enhances the ability that jumps out of the local optimum. Moreover, a dynamic tuning factor of piecewise linear chaotic mapping is utilized for the adjustment of the exploration space to improve the convergence performance. Finally, the validity and applicability of the proposed improved algorithm are evaluated by the challenging CEC 2017 function and three engineering optimization problems. The experimental comparative results of average, standard deviation, and Wilcoxon rank-sum tests reveal that the presented algorithm has excellent global optimality and convergence speed for most functions and engineering problems.

B cells play a pivotal role in autoimmunity not only by producing pathogenic autoantibodies but also by modulating immune responses via the production of cytokines and chemokines. The B cell-activating factor/a proliferation-inducing ligand (BAFF/APRIL) system promotes B cell survival and differentiation and thus plays a prominent role in the pathogenesis of autoimmune diseases. Currently, BAFF and APRIL inhibitors are in clinical trials for systemic lupus erythematosus with significant efficacy. However, several studies have demonstrated the efficacy of the BAFF/APRIL blockade which showed considerable variability in the response to B cell-targeted therapy. This may indicate substantial heterogeneity in the pathogenesis of autoimmune diseases. Therefore, objective markers that can predict the effect of BAFF/APRIL-blocking agents could be valuable to the precision medicine linked clinically and to cost-effective therapy.

The complement system is a major effector of humoral immunity and natural immunity. The complement system has three independent pathways of complement activation: a classical pathway, an alternative pathway, and a lectin pathway. These pathways converge to a common pathway that activates C3. This pathway also leads to the formation of various bioactive molecules such as C5a and the formation of membrane attack complex on the surface of target cells. In the past, the only preparations with anti-complementary action were C1 inhibitors (C1-INH), but an anti-C5 monoclonal antibody (eculizumab) appeared a few years ago, and this antibody has yielded encouraging results. In addition, a C5a receptor (C5aR) antagonist is in the clinical trial phase, and this antagonist should also prove efficacious. Anti-complement agents have garnered attention as a new treatment strategy for refractory inflammatory diseases.

Inflammatory and immune responses are generated locally by the selective invasion and accumulation of the immune cells into the lesion site. The infiltration process of the immune cells into the tissue from the blood through the vascular endothelial cells is closely regulated by a number of chemotactic factors and cell adhesion molecules. Fractalkine (FKN)/CX3CL1 is a membrane-bound chemokine possessing a chemokine/mucin hybrid structure and a transmembrane domain and has a dual function as an adhesion molecule and a chemoattractant. FKN is mainly expressed on activated endothelial cells, activated fibroblasts, and osteoblasts. Its receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes, monocytes/macrophages, and osteoclasts. To date, a lot of key functional aspects of the FKN-CX3CR1 axis has been identified: (1) the rapid capture and firm adhesion of immune cells to vascular endothelial cells, (2) chemotaxis, (3) the enhancement of the transmigration to other chemokines, (4) the crawling behavior of the monocytes that patrol on vascular endothelial cells, (5) the retention of monocytes as the accessory cells of the inflamed endothelium to recruit inflammatory cells, and (6) the survival of the macrophage. In this review, we will focus on the pathological role of FKN in rheumatoid arthritis (RA) and the physiological role of FKN on osteoclast differentiation. Furthermore, we will discuss the therapeutic potential of anti-FKN mAb for RA patients and its distinct mode of action from other cytokine inhibitors.

Ornamental breeding has traditionally focused on improving novelty, yield, quality, and resistance to biotic or abiotic stress. However, achieving these goals has often required laborious crossbreeding, while precise breeding techniques have been underutilized. Fortunately, recent advancements in plant genome sequencing and editing technology have opened up exciting new frontiers for revolutionizing ornamental breeding. In this review, we provide an overview of the current state of ornamental transgenic breeding and propose four promising breeding strategies that have already proven successful in crop breeding and could be adapted for ornamental breeding with the help of genome editing. These strategies include recombination manipulation, haploid inducer creation, clonal seed production, and reverse breeding. We also discuss in detail the research progress, application status, and feasibility of each of these tactics.

Panax ginseng is widely used in Asian countries and its active constituents—ginsenosides—need to be systematically studied. However, only a small part of ginsenosides have been characterized in the roots and rhizomes of panax ginseng (RRPG) up to date, mainly because of a lack of the fragmentation ions of many more ginsenosides. In order to comprehensively identify ginsenosides in RRPG, molecular features of ginsenosides orienting precursor ions selection and targeted tandem mass spectrometry (MS/MS) analysis strategy were proposed in our study, in which the precursor ions were selected according to the molecular features of ginsenosides irrespective of their peak abundances, and targeted MS/MS analysis was then performed to obtain their fragmentation ions for substance characterization. Using this strategy, a total of 620 ginsenosides were successfully characterized in RRPG, including 309 protopanaxadiol-type ginsenosides, 258 protopanaxatriol-type ginsenosides and 53 oleanane-type ginsenosides. It is worth noting that, except for the known aglycones mass-to-charge ratio (m/z) 459, 475 and 455, twelve other aglycones, including m/z 509, 507, 493, 491, 489, 487, 477, 473, 461, 457, 443 and 441, were first reported in our experiment and they were probably the derivatizations of the protopanaxatriol and protopanaxadiol. Our study will not only help people to improve the cognition of ginsenosides in RRPG, but will also play a guiding and reference role for the isolation and characterization of potentially new ginsenosides from RRPG.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been known as a hematopoietic growth factor and immune modulator. Recent studies revealed that GM-CSF also had pro-inflammatory functions and contributed to the pathogenicity of Th17 cells in the development of Th17-mediated autoimmune diseases. GM-CSF inhibition in some animal models of autoimmune diseases showed significant beneficial effects. Therefore, several agents targeting GM-CSF are being developed and are expected to be a useful strategy for the treatment of autoimmune diseases. Particularly, in clinical trials for rheumatoid arthritis (RA) patients, GM-CSF inhibition showed rapid and significant efficacy with no serious side effects. This article summarizes recent findings of GM-CSF and information of clinical trials targeting GM-CSF in autoimmune diseases.

Immunotherapy of cancer has made tremendous progress in recent years, as demonstrated by the remarkable clinical responses obtained from adoptive cell transfer (ACT) of patient-derived tumor infiltrating lymphocytes, chimeric antigen receptor (CAR)-modified T cells (CAR-T) and T cell receptor (TCR)-engineered T cells (TCR-T). TCR-T uses specific TCRS optimized for tumor engagement and can recognize epitopes derived from both cell-surface and intracellular targets, including tumor-associated antigens, cancer germline antigens, viral oncoproteins, and tumor-specific neoantigens (neoAgs) that are largely sequestered in the cytoplasm and nucleus of tumor cells. Moreover, as TCRS are naturally developed for sensitive antigen detection, they are able to recognize epitopes at far lower concentrations than required for CAR-T activation. Therefore, TCR-T holds great promise for the treatment of human cancers. In this focused review, we summarize basic, translational, and clinical insights into the challenges and opportunities of TCR-T. We review emerging strategies used in current ACT, point out limitations, and propose possible solutions. We highlight the importance of targeting tumor-specific neoAgs and outline a strategy of combining neoAg vaccines, checkpoint blockade therapy, and adoptive transfer of neoAg-specific TCR-T to produce a truly tumor-specific therapy, which is able to penetrate into solid tumors and resist the immunosuppressive tumor microenvironment. We believe such a combination approach should lead to a significant improvement in cancer immunotherapies, especially for solid tumors, and may provide a general strategy for the eradication of multiple cancers.

The induction of mitochondrial permeability transition-driven necrosis (MPTDN) is therapeutically relevant in various cancers. However, few studies have explored the role of MPTDN-related genes (MPTDNRGs) in lung adenocarcinoma (LUAD). Therefore, this study investigated the regulatory mechanisms of MPTDNRGs in LUAD. This study was based on The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD), GSE31210, and MPTDNRGs. First, the genes obtained from TCGA-LUAD were intersected through differential expression analysis and weighted gene co-expression network analysis (WGCNA) to obtain the candidate gene. An knockdown cell model was constructed using LUAD cells, and cell-related phenotypic experiments, including proliferation and apoptosis, were performed. The integrity of the mitochondrial structure was observed using electron microscopy, and the mitochondrial membrane potential was detected using a JC-1 probe. A total of 82 candidate genes were identified by intersecting 3,231 differentially expressed genes with 566 key module genes. Subsequently, three prognostic genes ( , , and ) were further screened. and were significantly expressed in the LUAD group, whereas the opposite was true for . studies indicated that knockdown significantly inhibited the proliferation of LUAD cells and induced necrosis in these cells. Electron microscopy found that the mitochondrial structure was disrupted after knockdown. The JC-1 probe indicated that the mitochondrial membrane potential in the -knockdown group was significantly reduced, suggesting impaired mitochondrial function. , , and have been identified as being associated with MPTDN in LUAD cells. knockdown may suppress mitochondrial permeability transition through specific pathways, thereby driving LUAD cell necrosis and providing potential targets for subsequent LUAD treatment.

CITATION: Tewari, V. P., Verma, R. K. & Von Gadow, K. 2017. Climate change effects in the Western Himalayan ecosystems of India : evidence and strategies. Forest Ecosystems, 4:13, doi:10.1186/s40663-017-0100-4.