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The sampling results that meet the test accuracy requirements suggest the possibility of realizing an intelligent sampling method. In addition, the representative of the interlayer cluster center is validated. Finally, the comparison results with the traditional stratified sampling method prove that the proposed method has better stability.Antimicrobial peptides (AMPs) are promising alternatives to classical antibiotics for the treatment of drug-resistant infections. Due to their versatility and unlimited sequence space, AMPs can be rationally designed by modulating physicochemical determinants to favor desired biological parameters and turned into novel therapeutics. In this study, we utilized key structural and physicochemical parameters, in combination with rational engineering, to design novel short α-helical hybrid peptides inspired by the well-known natural peptides, cathelicidin and aurein. By comparing homologous sequences and abstracting the conserved residue type, sequence templates of cathelicidin (P0) and aurein (A0) were obtained. Two peptide derivatives, P7 and A3, were generated by amino acid substitution based on their residue composition and distribution. In order to enhance antimicrobial activity, a hybrid analog of P7A3 was designed. The results demonstrated that P7A3 had higher antibacterial activity than the parental peptides with unexpectedly high hemolytic activity. Strikingly, C-terminal truncation of hybrid peptides containing only the α-helical segment (PA-18) and shorter derivatives confer potent antimicrobial activity with reduced hemolytic activity in a length-dependent manner. Among all, PA-13, showed remarkable broad-spectrum antibacterial activity, especially against Pseudomonas aeruginosa with no toxicity. PA-13 maintained antimicrobial activity in the presence of physiological salts and displayed rapid binding and penetration activity which resulted in membrane depolarization and permeabilization. Moreover, PA-13 showed an anti-inflammatory response via lipopolysaccharide (LPS) neutralization with dose-dependent, inhibiting, LPS-mediated Toll-like receptor activation. This study revealed the therapeutic potency of a novel hybrid peptide, and supports the use of rational design in development of new antibacterial agents.We have studied the charge and spin thermopower systematically in a ferromagnetic junction of graphene-like zigzag nanoribbon modified by two on-site disorders in the tight-binding model. Symmetries of the transmission spectra and geometry configuration of the two disorders are important factors in determining the thermoelectric properties of the system. Conditions to achieve pure charge and pure spin thermopower are discussed from the perspective of symmetry. Symmetry breaking is required sometimes to obtain large figure of merit. The type and strength of the disorders can be used to further manipulate the spin polarization of thermal current. Disorders inside nanoribbon instead of on edge can then be used to finely tune the performance of the junction. click here The results may have great application value in designing thermoelectric devices.Reversible structural transformations of porous coordination frameworks in response to external stimuli such as light, electrical potential, guest inclusion or pressure, amongst others, have been the subject of intense interest for applications in sensing, switching and molecular separations. Here we report a coordination framework based on an electroactive tetrathiafulvalene exhibiting a reversible single crystal-to-single crystal double [2 + 2] photocyclisation, leading to profound differences in the electrochemical, optical and mechanical properties of the material upon light irradiation. Electrochemical and in situ spectroelectrochemical measurements, in combination with in situ light-irradiated Raman spectroscopy and atomic force microscopy, revealed the variable mechanical properties of the framework that were supported using Density Functional Theory calculations. The reversible structural transformation points towards a plethora of potential applications for coordination frameworks in photo-mechanical and photoelectrochemical devices, such as light-driven actuators and photo-valves for targeted drug delivery.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Alpha defensins are anti-microbial peptides of the innate immune system. The defensin A1 and A3 genes are located in a repeat array of variable copy number (the DEFA1A3 locus) and encode the human neutrophil peptides 1, 2 and 3. The possibility that copy number variation (CNV) may be associated with infection susceptibility and autoimmune pathology motivated the study of DEFA1A3 CNV across populations. We enhanced two existing methods (one qPCR-based and one sequencing-based) to enable copy number estimation that discriminates between DEFA1 and DEFA3 genes. We used these methods to quantify A1/A3 copy number variation in 2504 samples from the 1000 Genomes high-coverage dataset as well as performing FiberFISH assays on selected samples to visualize the haplotypes. These methods produce accurate estimates and show that there are substantial differences between populations. The African population is a clear outlier with a high frequency of the ancestral pure DEFA1 haplotype, but also harbours exceptionally long haplotypes of 24 copies of both DEFA1 and DEFA3, whilst the East Asian population displays the highest mean level of DEFA3 copy number. Further, our findings demonstrate that qPCR can be an accurate method for CNV estimation and that defensins substantially extend the known range of copy number variation for a human protein-coding gene.Chemotherapy remains the gold standard for advanced cancer. Pemetrexed, a chemotherapeutic agent used in non-small cell lung cancer, can induce significant side effects in patients. Although microbiota's role in the efficacy and/or toxicity of chemotherapy agents has been demonstrated, the impacts of pemetrexed on the gut microbiota and on gastrointestinal inflammation remain unknown. The objective of this study was to evaluate the impact of pemetrexed and the tumor graft on the gut microbiota composition in immunodeficient mice. The faecal microbiota composition was studied with metabarcoding before, 24-h and one week after treatment. The colon epithelial barrier integrity was evaluated by histological examination, intestinal permeability measurement, and selected cytokines quantification. The tumor graft induced some variations in the microbiota composition. Pemetrexed further increased the relative abundance of Enterobacteriaceae and 3 families from the Firmicutes phylum Enterococcaceae, Lactobacillaceae and Streptococcaceae.
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