•single layer multi-component absorbers with magnetodielectric fillers were synthesized.•Co/C MOF/doped Barium hexaferrite/MWCNTs composites were successfully prepared.•The sample with 55 wt% loading ...exhibits optimal RL characteristics.•RLmin of the sample is −26 dB with a broad effective bandwidth of 4.2 GHz at 2.5 mm.•Multiple attenuation of this customized heterogeneous structures enhanced microwave absorption performance.
The microwave absorber composites as the combinations of MWCNTs, Ba-hexaferrite and Co/C particles were prepared. For Co/C synthesis, firstly, the Co-based MOF (ZIF-67) was synthesized through the solvothermal method and secondly, the ZIF-67calcined at 500 °C to obtain Co/C particles. In addition, the BaCoTiFe10O19 powder was synthesized via the hydrothermal method. The structural and morphological analysis were carried out by X-ray diffractometer (XRD), transmission electron microscope (TEM) and scanning electron microscope (SEM). The permeability and permittivity values of composites were investigated in the range of X band frequency (8.2–12.4 GHz). The electromagnetic (EM) wave absorption performance of composites was evaluated by using values of the permeability and permittivity values. It was demonstrated that the EM absorption performance of composites was enhanced by the loading MWCNTs. The combination of MWCNT with Ba-M and Co/C increased the magnetic and dielectric losses due to the enhance in both polarization and surface area. The minimum reflection loss (RL) of CBM.70.29.1 reached -34 dB with effective bandwidth (<-10 dB) in the range of X band frequency for matching thicknesses of 3.1 mm.
Antimicrobial resistance has been seriously threatening human health, and discovering new antimicrobial agents from the natural resource is still an important pathway among various strategies to ...prevent resistance. Guanidine-containing polyhydroxyl macrolides, containing a polyhydroxyl lactone ring and a guanidyl side chain, can be produced by many actinomycetes and have been proved to possess many bioactivities, especially broad-spectrum antibacterial and antifungal activities. To explore the potential of these compounds to be developed into new antimicrobial agents, a review on their structural diversities, spectroscopic characterizations, bioactivities, acute toxicities, antimicrobial mechanisms, and the structure-activity relationship was first performed based on the summaries and analyses of related publications from 1959 to 2019. A total of 63 guanidine-containing polyhydroxyl macrolides were reported, including 46 prototype compounds isolated from 33 marine and terrestrial actinomycetes and 17 structural derivatives. Combining with their antimicrobial mechanisms, structure-activity relationship analyses indicated that the terminal guanidine group and lactone ring of these compounds are vital for their antibacterial and antifungal activities. Further, based on their bioactivities and toxicity analyses, the discovery of guanidyl side-chain targeting to lipoteichoic acid of
indicated that these compounds have a great potency to be developed into antimicrobial and anti-inflammatory drugs.
Alzheimer’s disease (AD) is one of the most complicated progressive neurodegeneration diseases that involve many genes, proteins, and their complex interactions. No effective medicines or treatments ...are available yet to stop or reverse the progression of the disease due to its polygenic nature. To facilitate discovery of new AD drugs and better understand the AD neurosignaling pathways involved, we have constructed an Alzheimer’s disease domain-specific chemogenomics knowledgebase, AlzPlatform (www.cbligand.org/AD/) with cloud computing and sourcing functions. AlzPlatform is implemented with powerful computational algorithms, including our established TargetHunter, HTDocking, and BBB Predictor for target identification and polypharmacology analysis for AD research. The platform has assembled various AD-related chemogenomics data records, including 928 genes and 320 proteins related to AD, 194 AD drugs approved or in clinical trials, and 405 188 chemicals associated with 1 023 137 records of reported bioactivities from 38 284 corresponding bioassays and 10 050 references. Furthermore, we have demonstrated the application of the AlzPlatform in three case studies for identification of multitargets and polypharmacology analysis of FDA-approved drugs and also for screening and prediction of new AD active small chemical molecules and potential novel AD drug targets by our established TargetHunter and/or HTDocking programs. The predictions were confirmed by reported bioactivity data and our in vitro experimental validation. Overall, AlzPlatform will enrich our knowledge for AD target identification, drug discovery, and polypharmacology analyses and, also, facilitate the chemogenomics data sharing and information exchange/communications in aid of new anti-AD drug discovery and development.
Experimental works have exposed that Al-doping in the structure of ZnO nanostructures intensely increases their electronic sensitivity toward various chemicals. Herein, density functional theory ...calculations were employed to inspect the Al-doping effect on the sensitivity of a ZnO nanosheet (ZnOS) to the isoniazid (IS) drug. The pristine ZnOS physically adsorbs an IS molecule with adsorption energy (E
ad
) of −6.8 kcal/mol, and the sensing response value of 2.3 at 298 K. Replacing a Zn atom by an Al atom strengthens the interaction, increasing the E
ad
to −20.8 kcal/mol. Also, the Al-doping significantly increases the sensing response value to 150.3 by rising the electrical conductivity of the sheet. A short recovery time of 11.3 s is predicted for the Al-ZnOS-based sensor. The water solvent somewhat strengthens the interaction of IS drug with the Al-ZnOS, increasing the sensing response from 150.3 to 175.8. We concluded that the Al-doping makes the ZnOS a promising sensor for IS drug detection.
Pharmacokinetics provides a scientific basis for drug product design, dosage regimen planning, understanding the body's action on the drug, and relating the time course of the drug in the body to its ...pharmacodynamics and/or toxic effects. Recently, naringin, a natural flavonoid, was approved for clinical trials as a first-class new drug product by the China Food and Drug Administration, owing to its nonclinical efficacy in relieving cough, reducing sputum, and low toxicity. Previous reports focused on the pharmacokinetic studies of naringin or its active metabolite naringenin in rats, which were scattered and insufficient because naringin was coadministered with mixtures such as herbs, fruits, and other traditional medicines. The purpose of this study was to evaluate the pharmacokinetics and metabolism of naringin and naringenin, following oral and intravenous administration of naringin in rats, dogs, and humans, which can be beneficial for new drug development.
Separate bioanalytical methods were developed and validated to determine the concentrations of naringin and its active metabolite naringenin in biological samples obtained from rats, dogs, and humans. Comprehensive nonclinical and clinical data were used to estimate the pharmacokinetic parameters of naringin and naringenin. Experiments included single-dose studies (oral and intravenous administration), multiple-dose studies, and an assessment of food-effects. Furthermore, the metabolism of naringin and naringenin was studied in rat and human liver and kidney microsomes. All biological samples were analyzed using liquid chromatography-tandem mass spectrometry.
The pharmacokinetic parameters of naringin and naringenin were calculated and the results show an insignificant influence of high-fat diet and insignificant accumulation of the drugs after multiple dosing. Twelve metabolites were detected in the liver and kidney microsomes of rats and humans; naringin metabolism was a complex process simultaneously catalyzed by multiple human enzymes. All evaluated species demonstrated differences in the pharmacokinetics and metabolism of naringin and naringenin.
The results can be used to design a dosage regimen, deepen understanding of mechanisms, and accelerate new drug development.
http://www.chinadrugtrials.org.cn/eap/main, identifiers CTR20130704 and CTR20190127.
Display omitted
•W-Ag matrix composites were fabricated by designed dual-metal-layer coated powders.•The Cu-Ag coating promotes the sintering process and favors the low-temperature densification of ...W-Ag matrix composites.•The mechanical properties have enhanced due to the introduction of Cu-Ag coating.
In this study, W-Ag matrix composites were fabricated by a relatively low temperature (750 °C) via designing dual-metal-layer (Cu and Ag) coated W powders. The effects of Cu and Ag coated W powders on the densification, microstructure and properties of the composites were investigated. The results indicated that the Cu-Ag coating promotes the sintering process and favors the low-temperature densification of W-Ag matrix composites. Moreover, the Cu-Ag coating benefited the formation of Cu-Ag solution and improved the interfacial bonding. The hardness of W-Ag matrix composites was increased to 260.0 HV by adjusting the composition of the material, and compressive strength can reach 799 MPa. The electrical conductivity can reach 45.0% IACS.
Lipoteichoic acid (LTA) plays an essential role in bacterial growth and resistance to antibiotics, and LTA synthetase (LtaS) was considered as an attractive target for combating Gram-positive ...infections. Azalomycin F, a natural guanidyl-containing polyhydroxy macrolide, can target the LTA of
. Using various technologies including enzyme-linked immunosorbent assay, transmission electron microscope, proteomics, and parallel reaction monitoring, here, the experimental results indicated that azalomycin F can accelerate the LTA release and disrupt the cell envelope, which would also lead to the feedback upregulation on the expressions of LtaS and other related enzymes. Simultaneously, the reconstituted enzyme activity evaluations showed that azalomycin F can significantly inhibit the extracellular catalytic domain of LtaS (eLtaS), while this was vague for LtaS embedded in the liposomes. Subsequently, the fluorescence analyses for five incubation systems containing azalomycin F and eLtaS or the LtaS-embedded liposome indicated that azalomcyin F can spontaneously bind to the active center of LtaS. Combining the mass spectroscopy analyses and the molecular dockings, the results further indicated that this interaction involves the binding sites of substrates and the LTA prolongation, especially the residues Lys299, Phe353, Trp354 and His416. All these suggested that azalomycin F has multiple antibacterial mechanisms against
. It can not only inhibit LTA biosynthesis through the interactions of its guanidyl side chain with the active center of LtaS but also disrupt the cell envelope through the synergistic effect of accelerating the LTA release, damaging the cell membrane, and electrostatically interacting with LTA. Simultaneously, these antibacterial mechanisms exhibit a synergistic inhibition effect on
cells, which would eventually cause the cellular autolysis.
Extracellular vesicles (EVs)-mediated epithelium-macrophage crosstalk has been proved to maintain lung homeostasis in cigarette smoke-induced lung diseases such as chronic obstructive pulmonary ...disease (COPD). In our previous study, we found that EVs derived from cigarette smoke extract (CSE) treated BEAS-2B promoted M1 macrophage polarization, which probably accelerated the development of inflammatory responses. Naringenin has been proved to suppress M1 macrophage polarization, but whether naringenin regulates macrophage polarization mediated by EVs has not been reported. In this study, we firstly found that EVs derived from naringenin and CSE co-treated BEAS-2B significantly inhibited the expression of CD86 and CD80 and the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, inducible nitric oxide synthase (iNOS), and IL-12 in macrophage induced by EVs derived from CSE-treated BEAS-2B. Further research revealed that naringenin downregulated BEAS-2B-derived EVs miR-21-3p which targeted phosphatase and tensin homolog deleted on chromosome ten/protein kinase B (PTEN/AKT) cascade in macrophages and then suppressed M1 macrophage polarization. Subsequent proteomics suggested that naringenin decreased BEAS-2B-derived EVs poly ADP-ribose polymerase (PARP)1 expression thereby suppressing M1 macrophage polarization probably. Our study provides novel pharmacological references for the mechanism of naringenin in the treatment of cigarette smoke-induced lung inflammatory diseases.
Naringenin is found mainly in citrus fruits, and is thought to be beneficial in the prevention and control of lung diseases. This study aims to investigate the mechanisms of naringenin against the ...damage in the lung caused by cigarette smoke. A system bioinformatic approach was proposed to predict the mechanisms of naringenin for protecting lung health. Then, we validated this prediction in BEAS-2B cells treated with cigarette smoke extract (CSE). System bioinformatic analysis indicated that naringenin exhibits protective effects on lung through the inhibition of inflammation and suppression of oxidative stress based on a multi-pathways network, mainly including oxidative stress pathway, Nrf2 pathway, Lung fibrosis pathway, IL-3 signaling pathway, and Aryl hydrocarbon receptor pathway. The in vitro results showed that naringenin significantly attenuated CSE-induced up-regulation of IL-8 and TNF-α. CSE stimulation increased the mRNA expressions of Nrf2, HO-1, and NQO1; the levels of total protein and nuclear protein of Nrf2; and the activity of SOD on days 2 and 4; but decreased these indexes on day 6. Naringenin can balance the antioxidant system by regulating Nrf2 and its downstream genes, preliminarily validating that Nrf2 pathway is involved in the protection offered by naringenin against cigarette smoke-induced damage to the lung. It suggests that dietary naringenin shows possible potential use in the management of lung health.
PDF
