An increasing demand for freshwater inspires further understanding of the mechanism of water diffusion in reverse-osmosis membranes for the development of high-performance membranes for desalination. Water diffusion has a close relationship with the structural and dynamical characteristics of hydrogen bonds, which is not well-understood for the confining environment inside the polyamide membrane at the molecular level. In this work, an atomistic model of a highly cross-linked polyamide membrane was built with an equilibrated mixture of m-phenylenediamine and trimesoyl chloride monomers. The structure and dynamics of water in the regions from the bulk phase to the membrane interior were investigated by molecular dynamics simulations. Explicit hydrogen bond criteria were determined for hydrogen-bonding analysis. The local distribution and orientation of water reveal that the hydrogen-bonding affinity of the hydrophilic functional groups of polymers inhibits water diffusion inside the membrane. The affinity helps to produce percolated water channels across the membrane. The hydrogen-bonding structures of water in different regions indicate dehydration is required for the entry of water into the polyamide membrane, which dominates water flux across the membrane. This paper not only deepens the understanding of the structure and dynamics of water confined in the polyamide membrane but also stimulates the future work on high-performance reverse-osmosis membranes.
Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations in humans and play a major role in the genetics of human phenotype variation and the genetic basis of human complex diseases. Recently, there is considerable interest in understanding the possible role of the CYP11B2 gene with corticosterone methyl oxidase deficiency, primary aldosteronism, and cardio-cerebro-vascular diseases. Hence, the elucidation of the function and molecular dynamic behavior of CYP11B2 mutations is crucial in current genomics. In this study, we investigated the pathogenic effect of 51 nsSNPs and 26 UTR SNPs in the CYP11B2 gene through computational platforms. Using a combination of SIFT, PolyPhen, I-Mutant Suite, and ConSurf server, four nsSNPs (F487V, V129M, T498A, and V403E) were identified to potentially affect the structure, function, and activity of the CYP11B2 protein. Furthermore, molecular dynamics simulation and structure analyses also confirmed the impact of these nsSNPs on the stability and secondary properties of the CYP11B2 protein. Additionally, utilizing the UTRscan, MirSNP, PolymiRTS and miRNASNP, three SNPs in the 3′UTR region were predicted to exhibit a pattern change in the upstream open reading frames (uORF), and eight microRNA binding sites were found to be highly affected due to 3′UTR SNPs. This cataloguing of deleterious SNPs is essential for narrowing down the number of CYP11B2 mutations to be screened in genetic association studies and for a better understanding of the functional and structural aspects of the CYP11B2 protein.
The objective of the research was to investigate the function of endothelial progenitor cells (EPCs) in the conditions of high glucose and lipids, which has been widely used to mimic the metabolic disorder that occurs in type 2 diabetic mellitus, and further to verify the role of PGC-1α and SIRT1, cellular energy metabolism regulators, in the process of senescence of EPCs with these combined stimuli. Circulating EPCs were incubated in absence or presence of high glucose (25 mM), FFA (200 µM) or both. EPCs senescence was assessed by β-galactosidase staining, EPCs telomerase activity was measured by telomeric repeat ampli-fication protocol assay, in vitro angiogenesis assay and MTT assays were performed to assess angiogenesis and proliferation ability of EPCs. The results showed that combined stimuli inhibited EPCs reendothelialization ability in vitro, accelerated EPCs senescence and decreased the telomerase activity. Meanwhile, with combined stimuli, the expression of PGC-1α increased whereas SIRT1 expression decreased in EPCs accompanied by activation of P53/P21 signaling pathway. Conversely, transfection of EPCs with PGC-1α-siRNA rescued EPCs premature senescence and up-regulated SIRT1 and decreased P53/P21 expression, correlating closely with the down-regulation of PGC-1α itself. In addition, the combined stimuli induced up-regulation of PGC-1α expression was partly mediated by ROS and P38 signaling pathway. Overall, the data presented here identify PGC-1α as a potent negative regulator of EPCs' senescence under combined stimuli, which is partly mediated by SIRT1/P53/P21 signaling pathway.
Kimura disease (KD) is a rare and benign chronic inflammatory disease of unknown cause. It is characterized by subcutaneous granuloma of soft tissues in the head and neck region, increased eosinophil count, and elevated serum IgE. Currently, no definitive treatments are recommended. A 57-year-old Chinese man was diagnosed with KD after 7 years of slow subcutaneous masses growth. The patient underwent treatment of oral glucocorticoids for 1 year, but the masses recurred as the dosage was tapered down. Subsequent anti-IgE therapy of omalizumab administered subcutaneously at 450 mg/day at a 4-week interval did not show improvement. The size of masses and serum IgE and circulating eosinophils did not decrease significantly after 19 cycles of continuous treatment. Ultimately, switched strategy of dupilumab was applied at an initial dose of 600 mg, followed by 300 mg every 2 weeks for 4 months. This treatment demonstrated dramatical effects with reduced masses in each area and fast dropdown of eosinophil counts, while the high level of serum IgE remained without changes. Recently, different biologics including anti-IgE, anti-IL-5, and anti-IL-4/IL-13 have been applied to treat KD with satisfied results and help to explore the pathogenesis of this rare disease. To our knowledge, this is the first report that demonstrates the effects of two different biologics in the same patient and reveals the impressive clinical efficacy of dupilumab to treat KD independent of IgE. Therefore, further investigation of the underlying mechanism and the development of diagnosis and treatment of KD is valuable.
Miscanthus sinensis is a potential biofuel that is distributed widely in China, but with difficulties for decomposition and utilization due to the complexity of its fibrous cell walls. To detect whether M. sinensis could increase the population of rumen fibrolitic microbes, two16S rRNA gene libraries were constructed using ruminal samples from Xiangxi yellow cattle fed with either common mixed feedstuff (group C) or M. sinensis (group M), and the diversity of ruminal bacteria and archaea in the rumens of cattle of both groups was identified. Based on the comparative analysis of these two groups, the microbial composition in group C/M was found to be: Bacteroidetes (16.33 %/28.15 %), Firmicutes (68.88 %/60.92 %), Proteobacteria (10.71 %/3.78 %), Planctomycetes (0/0.84 %), Lentisphaerae (0/0.42 %), Spirochaetes (1.02 %/0) in the Bacteria domain and Thermoplasmata (13.09 %/46.67 %), Methanomicrobia (57.14 %/12.22 %) and uncultured archaea (29.76 %/41.11 %) in the Archaea domain, respectively. Moreover, through phylogenetic analysis, we also detected the increase of Bacteroidetes and the decrease of Methanomicrobia in group M. These results indicated that feeding cattle with M. sinensis will change the microbial composition in the rumen; the increased bacteroidetes may be responsible for digesting M. sinensis, which will benefit us in further screening for potentially valuable bio-enzymes.
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