Coumarin compounds represent an important type of naturally occurring and synthetic oxygen-containing heterocycles with typical benzopyrone framework. This type of special benzopyrone structure ...enables its derivatives readily interact with a diversity of enzymes and receptors in organisms through weak bond interactions, thereby exhibit wide potentiality as medicinal drugs. So far, some coumarin-based drugs such as anticoagulant and antineurodegenerative agents have been extensively used in clinic. Coumarin-containing supramolecular medicinal agents as a new increasing expansion of supramolecular chemistry in pharmaceutical science have also been actively investigated in recent years. Coumarin-derived artificial ion receptors, fluorescent probes and biological stains are growing quickly and have a variety of potential applications in monitoring timely enzyme activity, complex biological events as well as accurate pharmacological and pharmacokinetic properties. This review provides a systematic summary and insight of the whole range of medicinal chemistry in the current developments of coumarin compounds as anticoagulant, antineurodegenerative, anticancer, antioxidative, antibacterial, antifungal, antiviral, antiparasitic, antiinflammatory and analgesic, antidiabetic, antidepressive and other bioactive agents as well as supramolecular medicinal drugs, diagnostic agents and pathologic probes, and biological stains. Some rational design strategies, structure-activity relationships and action mechanisms are discussed. The perspectives of the future development of coumarinbased medicinal chemistry are also presented.
Photocatalysis is one of the most important chemical methods to mitigate the energy and environmental crisis via converting inexhaustible solar energy into clean chemical potential. The general ...history of the development of photocatalysis based on porous metal–organic frameworks (MOFs) is simply divided into three branches with a focus placed on the distinct structural role of the photocatalytic center: the inorganic cluster nodes, the organic linkers, and the guests in the pores of MOFs. In each branch, these photocatalytic centers are considered to be monodispersed within the crystal lattices with the other two structure roles regularly distributed to isolate the active centers and sometimes to provide more functions other than photoactivity. This distinctive nature has rendered MOFs as promising candidates for photocatalysis not only because they combine the benefits of heterogeneous catalysis and homogeneous catalysis but also because they facilitate the possibility of merging multifunctional catalytic sites for concerted or cascade photocatalysis. The design strategy and improvement approaches for MOF-based photocatalysts are also introduced with an emphasis on structure. Our intention is for this comprehensive view of MOFs-involved photocatalysts to inspire new ideas for designing heterogeneous photocatalysts toward the better utilization of solar energy.
Abiotic stresses, such as low or high temperature, deficient or excessive water, high salinity, heavy metals, and ultraviolet radiation, are hostile to plant growth and development, leading to great ...crop yield penalty worldwide. It is getting imperative to equip crops with multistress tolerance to relieve the pressure of environmental changes and to meet the demand of population growth, as different abiotic stresses usually arise together in the field. The feasibility is raised as land plants actually have established more generalized defenses against abiotic stresses, including the cuticle outside plants, together with unsaturated fatty acids, reactive species scavengers, molecular chaperones, and compatible solutes inside cells. In stress response, they are orchestrated by a complex regulatory network involving upstream signaling molecules including stress hormones, reactive oxygen species, gasotransmitters, polyamines, phytochromes, and calcium, as well as downstream gene regulation factors, particularly transcription factors. In this review, we aimed at presenting an overview of these defensive systems and the regulatory network, with an eye to their practical potential via genetic engineering and/or exogenous application.
Main observation and conclusion
Novel quinazolonthiazoles were designed and synthesized as new potential antimicrobial agents by facile multi‐step procedure from o‐aminobenzoic acids and ...2‐acetylthiazole. A series of biological evaluation showed that compound 7d was the most effective quinazolonethiazole with superior activity to reference drugs chloramphenicol and norfloxacin. This active molecule displayed unobvious bacterial resistance against P. aeruginosa, the low toxicity to normal hepatocytes, suitable pharmacokinetics and drug‐likeness. The preliminary biological interaction suggested that quinazolonethiazole 7d might induce bacterial death by disturbing the membrane permeability, whilst preventing bacteria from growth by integrating into DNA and binding with topoisomerase IV. These findings provided significant background for the further development of quinazolonethiazoles as new potential drugs in combating drug‐resistant pathogens.
A novel class of potential antimicrobial quiazolonethiazoles were developed by multistep synthetic process and their biological evaluation suggested that quiazolonethiazoles could provide the meritorious groundwork of future studies as new antimicrobial agents in fighting pathogenic organism.
This paper investigates the physical layer security problem of cognitive decode-and-forward relay networks over Nakagami-m fading channels. We consider the relaying communication between one ...secondary user (SU) source and one SU destination by using an opportunistic relay selection from multiple SU relays and sharing the licensed spectrum of multiple primary users (PUs) in the underlay network. While the transmission between the SUs imposes interference on each PU, the relayed transmission is intercepted by one SU eavesdropper. In the absence of the eavesdropper's channel state information, the relay selection is based on the largest channel gain of relay-to-destination link, which is assumed to be outdated due to feedback delay. We derive the exact probability of non-zero secrecy capacity and the exact secrecy outage probability (SOP) in the closed form. Furthermore, we derive the asymptotic SOP in two different cases, and explicitly show the effects of system parameters on the secrecy diversity order and the secrecy diversity gain, respectively. Both asymptotic analysis and simulation results show that the secrecy performance can be improved by increasing either the number of relays or the Nakagami parameter of the legitimate relay channels, whereas the secrecy diversity gain deteriorates as the number of the PUs increases.
Only a small number of function evaluations can be afforded in many real-world multiobjective optimization problems (MOPs) where the function evaluations are economically/computationally expensive. ...Such problems pose great challenges to most existing multiobjective evolutionary algorithms (EAs), which require a large number of function evaluations for optimization. Surrogate-assisted EAs (SAEAs) have been employed to solve expensive MOPs. Specifically, a certain number of expensive function evaluations are used to build computationally cheap surrogate models for assisting the optimization process without conducting expensive function evaluations. The infill sampling criteria in most existing SAEAs take all requirements on convergence, diversity, and model uncertainty into account, which is, however, not the most efficient in exploiting the limited computational budget. Thus, this article proposes a Kriging-assisted two-archive EA for expensive many-objective optimization. The proposed algorithm uses one influential point-insensitive model to approximate each objective function. Moreover, an adaptive infill criterion that identifies the most important requirement on convergence, diversity, or uncertainty is proposed to determine an appropriate sampling strategy for reevaluations using the expensive objective functions. The experimental results on a set of expensive multi/many-objective test problems have demonstrated its superiority over five state-of-the-art SAEAs.
Apoptosis resistance is to a large extent a major obstacle leading to chemotherapy failure during cancer treatment. Bypassing the apoptotic pathway to induce cancer cell death is considered to be a ...promising approach to overcoming this problem. Necroptosis is a regulated necrotic cell death modality in a caspase-independent fashion and is mainly mediated by Receptor-Interacting Protein 1 (RIP1), RIP3, and Mixed Lineage Kinase Domain-Like (MLKL). Necroptosis serves as an alternative mode of programmed cell death overcoming apoptosis resistance and may trigger and amplify antitumor immunity in cancer therapy.The role of necroptosis in cancer is complicated. The expression of key regulators of the necroptotic pathway is generally downregulated in cancer cells, suggesting that cancer cells may also evade necroptosis to survive; however, in certain types of cancer, the expression level of key mediators is elevated. Necroptosis can elicit strong adaptive immune responses that may defend against tumor progression; however, the recruited inflammatory response may also promote tumorigenesis and cancer metastasis, and necroptosis may generate an immunosuppressive tumor microenvironment. Necroptosis also reportedly promotes oncogenesis and cancer metastasis despite evidence demonstrating its antimetastatic role in cancer. In addition, necroptotic microenvironments can direct lineage commitment to determine cancer subtype development in liver cancer. A plethora of compounds and drugs targeting necroptosis exhibit potential antitumor efficacy, but their clinical feasibility must be validated.Better knowledge of the necroptotic pathway mechanism and its physiological and pathological functions is urgently required to solve the remaining mysteries surrounding the role of necroptosis in cancer. In this review, we briefly introduce the molecular mechanism and characteristics of necroptosis, the interplay between necroptosis and other cell death mechanisms, crosstalk of necroptosis and metabolic signaling and detection methods. We also summarize the intricate role of necroptosis in tumor progression, cancer metastasis, prognosis of cancer patients, cancer immunity regulation, cancer subtype determination and cancer therapeutics.
In this paper, we propose a framework to accelerate the computational efficiency of evolutionary algorithms on large-scale multiobjective optimization. The main idea is to track the Pareto optimal ...set (PS) directly via problem reformulation. To begin with, the algorithm obtains a set of reference directions in the decision space and associates them with a set of weight variables for locating the PS. Afterwards, the original large-scale multiobjective optimization problem is reformulated into a low-dimensional single-objective optimization problem. In the reformulated problem, the decision space is reconstructed by the weight variables and the objective space is reduced by an indicator function. Thanks to the low dimensionality of the weight variables and reduced objective space, a set of quasi-optimal solutions can be obtained efficiently. Finally, a multiobjective evolutionary algorithm is used to spread the quasi-optimal solutions over the approximate Pareto optimal front evenly. Experiments have been conducted on a variety of large-scale multiobjective problems with up to 5000 decision variables. Four different types of representative algorithms are embedded into the proposed framework and compared with their original versions, respectively. Furthermore, the proposed framework has been compared with two state-of-the-art algorithms for large-scale multiobjective optimization. The experimental results have demonstrated the significant improvement benefited from the framework in terms of its performance and computational efficiency in large-scale multiobjective optimization.
A series of new coumarin-based 1,2,4-triazoles were synthesized and some of them displayed comparable or even better antibacterial and antifungal efficacy compared to reference drugs Enoxacin, ...Chloromycin and Fluconazole.
A series of new coumarin-based 1,2,4-triazole derivatives were designed, synthesized and evaluated for their antimicrobial activities in vitro against four Gram-positive bacteria (
Staphylococcus aureus, MRSA,
Bacillus subtilis and
Micrococcus luteus), four Gram-negative bacteria (
Escherichia coli,
Proteus vulgaris,
Salmonella typhi and
Shigella dysenteriae) as well as three fungi (
Candida albicans,
Saccharomyces cerevisiae and
Aspergillus fumigatus) by two-fold serial dilution technique. The bioactive assay showed that some synthesized coumarin triazoles displayed comparable or even better antibacterial and antifungal efficacy in comparison with reference drugs Enoxacin, Chloromycin and Fluconazole. Coumarin bis-triazole compounds exhibited stronger antibacterial and antifungal efficiency than their corresponding mono-triazole derivatives.
Abstract
Background
Virtual reality (VR) is a frequently used intervention for the rehabilitation of individuals with neurological disorders.
Purpose
The aims of this review were to identify the ...short-term effect of VR on balance and to compare it with the effect of active interventions in individuals with Parkinson disease (PD).
Data Sources
Searches for relevant articles available in English were conducted using the MEDLINE (via PubMed), EMBASE, CENTRAL, CINAHL, PsycINFO, and Physiotherapy Evidence Database databases from inception until March 2019.
Study Selection
All randomized controlled trials comparing the effect of training with VR and the effect of training without VR on balance in individuals with PD were included.
Data Extraction
Two authors independently extracted data, assessed the methodological quality, and evaluated the evidence quality of the studies.
Data Synthesis
Fourteen randomized controlled trials including 574 individuals were eligible for qualitative analyses, and 12 of the studies involving 481 individuals were identified as being eligible for meta-analyses. Compared with active interventions, the use of VR improved the Berg Balance Scale score (mean difference = 1.23; 95% CI = 0.15 to 2.31; I2 = 56%). The Dynamic Gait Index and Functional Gait Assessment results were also significant after the sensitivity analyses (mean difference = 0.69; 95% CI = 0.12 to 1.26; I2 = 0%). Both provided moderate statistical evidence. However, the Timed “Up & Go” Test and the Activities-Specific Balance Confidence Scale did not differ significantly.
Limitations
Publication bias and diversity in the interventions were the main limitations.
Conclusions
Existing moderate evidence of the effectiveness of VR with the Berg Balance Scale, Dynamic Gait Index, and Functional Gait Assessment for individuals with PD was promising. Although the differences did not reach the clinically important change threshold, VR was comparable to active interventions and could be considered an adjuvant therapy for balance rehabilitation in individuals with PD.
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