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This article addresses the distributed model-free adaptive control (DMFAC) problem for learning nonlinear multiagent systems (MASs) subjected to denial-of-service (DoS) attacks. An improved dynamic linearization method is proposed to obtain an equivalent linear data model for learning systems. To alleviate the influence of DoS attacks, an attack compensation mechanism is developed. Based on the equivalent linear data model and the attack compensation mechanism, a novel learning-based DMFAC algorithm is developed to resist DoS attacks, which provides a unified framework to solve the leaderless consensus control, the leader-following consensus control, and the containment control problems. Finally, simulation examples are shown to illustrate the effectiveness of the developed DMFAC algorithm.

This article studies the observer-based event-triggered containment control problem for linear multiagent systems (MASs) under denial-of-service (DoS) attacks. In order to deal with situations where MASs states are unmeasurable, an improved separation method-based observer design method with less conservativeness is proposed to estimate MASs states. To save communication resources and achieve the containment control objective, a novel observer-based event-triggered containment controller design method based on observer states is proposed for MASs under the influence of DoS attacks, which can make the MASs resilient to DoS attacks. In addition, the Zeno behavior can be eliminated effectively by introducing a positive constant into the designed event-triggered mechanism. Finally, a practical example is presented to illustrate the effectiveness of the designed observer and the event-triggered containment controller.

The problem of the model-free adaptive resilient control (MFARC) for nonlinear cyber-physical systems (CPSs) suffered from aperiodic jamming attacks is investigated in this article. First, the MFARC framework subject to aperiodic jamming attacks is established, and an intermediate variable method is introduced to avoid using the unavailable time-varying parameter and further eliminate an extra assumption on the sign limit of it. Then, a MFARC scheme is devised to track the desired output, where the problem of the tracking control can be transformed into solving a feasibility problem, and the controller parameters can be obtained with the aid of the linear matrix inequality technique. What is more, a novel attack compensation mechanism is developed in the MFARC scheme to mitigate the impact of aperiodic jamming attacks. In the last, an example is provided to verify the effectiveness of the devised MFARC scheme.

Aim Coregonus peled fillets were used as a model to evaluate the dominant bacterial growth of chilled fish during storage after shipping and interactions of selected bacterial strains. Methods and Results Coregonus peled fillets were transported by air and land in ice boxes about 48 h from aquatic products company in Xinjiang, China, to the laboratory located in Dalian, China. Both culture-dependent (plate counts on nonselective media) based on 16S rRNA gene sequencing and culture-independent (Illumina-MiSeq high-throughput sequencing) methods were used. To detect interactions among bacterial populations from chilled fish, the influence of 18 test strains on the growth of 12 indicator isolates was measured by a drop assay and in liquid culture medium broth. The results showed that bacterial counts exceeded 7.0 log CFU/g following storage for 4 days at 4 °C. When the bacterial counts exceeded 8.5 log CFU/g after 12 days, the predominant micro-organisms were Aeromonas, Pseudomonas, Carnobacterium, Psychrobacter and Shewanella, as measured by the culture-independent method. All test strains showed inhibiting effects on the growth of other strains in liquid culture. Pseudomonas isolates showed antibacterial activity for approximately 60% of the indicator strains on nutritional agar plates. The majority of test isolates enhancing indicator strain growth were the strains isolated on day 0. Conclusions High-throughput sequencing approach gives whole picture of bacterial communities in chilled C. peled fillets during storage, while growth interferences between selected bacterial strains illustrate the complexity of microbial interactions. Significance and Impact of the Study We determined the bacterial communities and growth interferences in chilled Coregonus peled after shipping and these are the first data concerning microbiota in C. peled using a culture-independent analysis. The present study will be useful for manufacture and preservation of C. peled products by providing with valuable information regarding microbiological spoilage of C. peled.

Background: Multimodal postoperative analgesia with intravenous ibuprofen can reduce the consumption of opioids and reduce the postoperative pain intensity. Recommended dose in the USA and Europe is 800 mg every 6 hours for the management of moderate to severe postoperative pain. The purpose of this study was to investigate whether 800 mg is needed in the Chinese population.Methods: This is a multicenter, randomized, controlled multi-center trial. Adult patients (18-65 years of age) scheduled for abdominal or orthopedic surgery under general anesthesia with endotracheal intubation were eligible. Subjects were randomized at a ratio of 1:1:1 to receive ibuprofen at 400 or 800 mg or saline every 6 hours for 48 hours after the operation. All subjects received morphine access through patient-controlled intravenous analgesia (PCIA) device, which was set as background infusion rate 0.5 mg/h, bolus 1 mg, 5-minute lock interval and 20-mg 4-hour limit. The primary endpoint was morphine consumption within the first 24 hours after surgery. Results: A total of 396 patients were enrolled (180 men, 216 women; 46±12.4 years of age; 106 patients receiving abdominal surgery, and 290 patients receiving orthopedic surgery). The number of patients was 131 in the placebo group, 132 in the 400-mg group, and 133 in the 800-mg group. The 3 groups did not differ in age, sex, BMI and the type of surgery. Median 24-hour morphine consumption was 39.1 mg (IQR: 29.7, 61.7) mg in the placebo control, 29.8 mg (IQR: 24.3, 43.7) mg in the 400-mg group, and 28.0 mg (IQR: 24.1, 35.9) in the 800-mg group (PConclusions: Intravenous ibuprofen at either 400 or 800 mg every 6 hours could reduce postoperative morphine consumption, with apparently equal efficacy in Chinese population.

Postmenopausal osteoporosis (PMOP) is a common metabolic bone disease in postmenopausal women in the Worldwide, and seriously affects the quality of life of middle-aged and elderly women. Therefore, there is an urgent need to discover a highly effective drug for PMOP treatment. In this study, ultra-high performance liquid tandem quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was used to analyze the urine metabolic profiling and potential biomarkers, the relevant metabolic network of PMOP rats, and further to evaluate the intervention effect of Eleutheroside E (EE) against PMOP. Using multivariate statistical analysis combined with UPLC-Q/TOF-MS, a total of 27 biomarkers were identified, which related with 16 metabolic pathways, mainly involving steroidogenesis, beta oxidation of very long chain fatty acids, glutathione metabolism, carnitine synthesis, estrone metabolism, oxidation of branched chain fatty acids, etc. After treatment of EE, these biomarkers were markedly regulated, mainly involving steroid hormone biosynthesis, arachidonic acid metabolism, primary bile acid biosynthesis, indicating that EE had the therapeutic effect on PMOP. This study identified the potential urine metabolic markers and related metabolic pathways of the PMOP, explained the metabolic effect and pharmacological mechanisms of EE against PMOP, and provided a basis for the pharmacological study of EE.

Objective To study the influence of over-expression of three functional genes involved in GC biosynthetic pathway, GuHMGR , GuSQS 1, and GuBAS on GC production. Methods Three plant expression vectors were constructed and transformed into Agrobacterium tumefaciens EHA105, which were used to infect Glycyrrhiza uralensis hypocotyls explants. After induction, selection, differentiation, culture, and transplantation, 12, 15, and 5 regenerated plants over-expressing GuHMGR , GuSQS 1, and GuBAS , were obtained, respectively. Results RT-PCR analysis showed these transgenic regenerated G. uralensis plants had 2–6 copies of GuHMGR , GuSQS 1, or GuBAS. HPLC analysis showed the contents of 18 α - and 18 β -GC in all transgenic regenerated samples were both higher than that in the blank control. With the increase of copy numbers of GuHMGR , GuSQS 1, and GuBAS , the contents of 18 α - and 18 β -GC were both increased in most samples. The highest 18 α - and 18 β -GC contents in transgenic regenerated plants were about 3.05 times and 2.80 times higher than that in the blank control, respectively. Conclusion Over-expression of the GuHMGR , GuSQS 1, and GuBAS genes enhance the accumulation of 18 α - and 18 β -GC in the roots and rhizomes of G. uralensis . We hope this work can lay a foundation for the molecular breeding research of G. uralensis and improving the quality of the roots and rhizomes of G. uralensis cultivars.

Context: Increasing incidence and impact of inflammatory diseases have encouraged the search of new pharmacological strategies to face them. Licorice has been used to treat inflammatory diseases since ancient times in China. Objective: To summarize the current knowledge on anti-inflammatory properties and mechanisms of compounds isolated from licorice, to introduce the traditional use, modern clinical trials and officially approved drugs, to evaluate the safety and to obtain new insights for further research of licorice. Methods: PubMed, Web of Science, Science Direct and ResearchGate were information sources for the search terms ‘licorice’, ‘licorice metabolites’, ‘anti-inflammatory’, ‘triterpenoids’, ‘flavonoids’ and their combinations, mainly from year 2010 to 2016 without language restriction. Studies were selected from Science Citation Index journals, in vitro studies with Jadad score less than 2 points and in vivo and clinical studies with experimental flaws were excluded. Results: Two hundred and ninety-five papers were searched and 93 papers were reviewed. Licorice extract, 3 triterpenes and 13 flavonoids exhibit evident anti-inflammatory properties mainly by decreasing TNF, MMPs, PGE2 and free radicals, which also explained its traditional applications in stimulating digestive system functions, eliminating phlegm, relieving coughing, nourishing qi and alleviating pain in TCM. Five hundred and fifty-four drugs containing licorice have been approved by CFDA. The side effect may due to the cortical hormone like action. Conclusion: Licorice and its natural compounds have demonstrated anti-inflammatory activities. More pharmacokinetic studies using different models with different dosages should be carried out, and the maximum tolerated dose is also critical for clinical use of licorice extract and purified compounds.

Context: Radix Bupleuri has been used in traditional Chinese medicine for over 2000 years with functions of relieving exterior syndrome, clearing heat, regulating liver-qi, and lifting yang-qi. More natural active compounds, especially saikosaponins, have been isolated from Radix Bupleuri, which possess various valuable pharmacological activities. Objective: To summarize the current knowledge on pharmacological activities, mechanisms and applications of extracts and saikosaponins isolated from Radix Bupleuri, and obtain new insights for further research and development of Radix Bupleuri. Methods: PubMed, Web of Science, Science Direct, Research Gate, Academic Journals and Google Scholar were used as information sources through the inclusion of the search terms ‘Radix Bupleuri’, ‘Bupleurum’, ‘saikosaponins’, ‘Radix Bupleuri preparation’, and their combinations, mainly from the year 2008 to 2016 without language restriction. Clinical preparations containing Radix Bupleuri were collected from official website of China Food and Drug Administration (CFDA). Results and conclusion: 296 papers were searched and 128 papers were reviewed. A broad spectrum of in vitro and in vivo research has proved that Radix Bupleuri extracts, saikosaponin a, saikosaponin d, saikosaponin c, and saikosaponin b2, exhibit evident anti-inflammatory, antitumor, antiviral, anti-allergic, immunoregulation, and neuroregulation activities mainly through NF-κB, MAPK or other pathways. 15 clinical preparations approved by CFDA remarkably broaden the application of Radix Bupleuri. The main side effect of Radix Bupleuri is liver damage when the dosage is excess, which indicates that the maximum tolerated dose is critical for clinical use of Radix Bupleuri extract and purified compounds.

Basic Fibroblast Growth Factor (bFGF/FGF2) is thought to play a decisive role in malignant progression. Aberrant expression of bFGF causes constitutive autocrine activation of its cognate receptor and autonomous growth of human melanoma cells or bFGF transformed fibroblasts in culture. It remains to be determined, however, whether the endogenous bFGF confers growth advantage to tumors and what are the downstream targets of the activated FGF receptor critical for its transforming capacity. We therefore transfected metastatic melanoma cells and bFGF transformed mouse fibroblasts with a dominant-negative mutant of the murine FGF receptor 1 (fgfr1/flg), comprising the extracellular and transmembrane domains but lacking the intracellular kinase domain (dnflg). Reverse transcriptase-PCR, 125I-bFGF binding and affinity labeling analyses show that the truncated receptor is targeted to the membrane and is expressed at much higher levels than the endogenous receptor in all of the selected clones. Expression of the dnflg dramatically reduces the basal as well as bFGF induced growth of these cells in vitro and also suppresses their tumorigenic potential in nude mice. The expression of the dnflg does not significantly alter the general level of tyrosyl-phosphorylated proteins in the trunsduced melanoma cells. Rather, a major downstream affected target is a Src-family kinase, whose activity, determined by an in vitro immune kinase assay, is stimulated in normal melanocytes by exogenous bFGF, and is markedly reduced in the dnflg-expressing melanoma cells. The present study demonstrates that direct interference with the activity of FGF receptors has a deleterious effect on cell proliferation and survival in vitro and in vivo leading to the suppression of melanoma tumor progression possibly through the inactivation of a Src-family kinase.

In the title compound, C19H15N3O3, the phthalimide group, dihydro­pyrazole ring and phenyl ring are all essentially planar. The dihedral angles between the phthalimide group and dihydro­pyrazole ring, and the phthalimide group and phenyl ring are 57.0 (2) and 46.3 (3)°, respectively.

Recent studies have demonstrated the existence of a soluble fibroblast growth factor (FGF) receptor type 1 (FGFR1) extracellular domain in the circulation and in vascular basement membranes. However, the process of FGFR1 ectodomain release from the plasma membrane is not known. Here we report that the 72-kDa gelatinase A (matrix metalloproteinase type 2, MMP2) can hydrolyze the Val368-Met369 peptide bond of the FGFR1 ectodomain, eight amino acids upstream of the transmembrane domain, thus releasing the entire extracellular domain. Similar results were obtained regardless of whether FGF was first bound to the receptor or not. The action of MMP2 abolished binding of FGF to an immobilized recombinant FGFR1 ectodomain fusion protein and to Chinese hamster ovary cells overexpressing FGFR1 The released recombinant FGFR1 ectodomain was able to bind FGF after MMP2 cleavage, suggesting that the cleaved soluble receptor maintained its FGF binding capacity. The activity of MMP2 could not be reproduced by the 92-kDa gelatinase B (MMP9) and was inhibited by tissue inhibitor of metalloproteinase type 2. These studies demonstrate that FGFR1 may be a specific target for MMP2 on the cell surface, yielding a soluble FGF receptor that may modulate the mitogenic and angiogenic activities of FGF.