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Antimicrobial peptides are widely acknowledged as an alternative class of antimicrobial agents. In this study, a lysine-rich scorpion peptide derivative Pacavin-5K was designed, which showed an improved antibacterial spectrum, significantly higher antibacterial activity, and lower toxicity compared to the native peptide. It also showed an improved thermal and serum stability. Notably, Pacavin-5K significantly decreased the bacterial counts in the wounded region in the mouse cutaneous infection model caused by Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, Pacavin-5K did not induce bacterial resistance associated with its antibacterial mechanism disrupting the membrane. Furthermore, Pacavin-5K could kill the S. aureus cells at the biofilm state. Overall, Pacavin-5K could be a potential alternative antibacterial agent against skin infection caused by S. aureus and P. aeruginosa. [Display omitted] • Pacavin-5K showed excellent antibacterial activity in vitro and in vivo. • Pacavin-5K showed excellent thermal and serum stability. • Pacavin-5K killed bacterial cells mainly by disrupting the membrane. • Pacavin-5K did not induce bacterial resistance. • Pacavin-5K could be a potent anti-infective agent against skin infection. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides have recently become extremely popular as a novel class of antimicrobial agents. AMP MK049518 (FLGLLGSVLGSVLPSIFK), identified from the crab-scorpion Didymocentrus krausi , only possesses significant antibacterial activity against Gram-positive bacteria. In this study, a derivative G2K–S3K was designed with an excellent antibacterial spectrum and significantly higher antibacterial activity compared to the natural peptide. G2K–S3K also demonstrated excellent serum- and thermal-stability and did not induce bacterial resistance. In the Staphylococcus aureus and Pseudomonas aeruginosa -induced skin infection in mice, G2K–S3K significantly decreased bacterial counts in the wound by topical application. Thus, G2K–S3K could be a potent topical anti-infective agent against the skin infection caused by S. aureus and P. aeruginosa. • Scorpion venoms have been good resources for the discovery of antimicrobial peptides. • A scorpion-derived peptide, G2K–S3K, with improved antibacterial spectrum and activity was designed in this study. • G2K–S3K showed excellent serum- and thermal-stability and did not induce bacterial resistance. • G2K–S3K could significantly decrease the counts of Staphylococcus aureus and Pseudomonas aeruginosa in the wounded region. • G2K–S3K could be a potent topical anti-infective agent against skin infection. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) are not only involved in individual growth and metabolism, but they are also associated with inflammation and homeostasis of articular cartilage and bone. Recent studies have identified the involvement of IGF-1 and IGFBP-3 in the development of rheumatoid arthritis (RA). Nevertheless, the results were inconsistent, and the relevant data were not synthetically assessed. Therefore, this review aimed to systematically evaluate the associations of serum IGF-1 and IGFBP-3 levels with the development of RA. Several databases were used to retrieve relevant publications (up to January 2018). Pooled standard mean difference (SMD) and 95% confidence interval (CI) were demonstrated using a forest plot. A total of 27 studies from 19 publications were included. Meta-analysis results showed that RA patients had lower serum IGF-1 levels when compared to controls (SMD = −0.650, 95% CI = −1.184 to −0.115, P =.017). However, there was no significant association between serum IGFBP-3 levels and RA (SMD = 0.590, 95% CI = −1.323 to 2.504, P =.545). Subgroup analyses further showed that serum IGF-1 levels in RA patients are discrepant in terms of race, age, and measurement type (all P <.05). In conclusion, the decreased levels of serum IGF-1 were closely associated with the development of RA. Future longitudinal studies are needed to validate the link between serum IGF-1 levels with RA pathogenesis as well as the effects of IGF-1 on RA treatment. [ABSTRACT FROM AUTHOR]

A simple and low-cost method for the synthesis of α -MnO 2 /C catalyst was proposed, in which KMnO 4 was reduced in-situ by cellulose in urea solution. The heterogeneous catalytic degradation of urea wastewater were carried out over α -MnO 2 /C. The effect of KMnO 4 -urea solution concentration on the structure and performance of the catalysts was investigated. The results indicate that δ -MnO 2 tends to curl and collapse into tunnel structure of α -MnO 2 as the concentration of KMnO 4 -urea solution increases, leading to α -MnO 2 is evenly distributed on carbon carrier. When the concentration of KMnO 4 -urea solution is appropriate, the catalyst has not only a large specific surface area but also high oxygen vacancy density, which is the key to be able to completely degrade the urea process wastewater. The reaction kinetics show that the catalytic hydrolysis of urea behaves as a pseudo-first-order reaction. A possible catalytic mechanism of urea hydrolysis over α -MnO 2 /C was proposed. In addition, the reusability experiments show that the α -MnO 2 /C catalyst has a good recycling ability. [Display omitted] • α -MnO 2 /C was synthesized through KMnO 4 in-situ reduced by cellulose. • The uniform distribution of MnO 2 on carbon carrier improves the utilization of MnO 2. • Mn3+ and oxygen vacancy over α -MnO 2 /C are critical for urea hydrolysis. • Urea in wastewater can be almost completely degraded using this catalyst. [ABSTRACT FROM AUTHOR]

Abstract Objective This study aimed to assess the association between two tag single nucleotide polymorphisms (SNPs) (rs68177277 and rs11624293) of G protein-coupled receptor 65 (GPR65) gene and ankylosing spondylitis (AS) susceptibility in a Chinese Han population. Methods 673 patients with AS diagnosed according to the modified New York criteria and 679 age- and gender-matched healthy controls were recruited. SNP genotyping for rs68177277 and rs11624293 polymorphisms were performed using the SNPscan technique. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Results Genotype and allele distribution of rs11624293 but not rs68177277 were significantly different between AS and controls (p = 0.004 and p = 0.002). Compared to the wild-type T/T genotype and T allele at rs11624293, the frequencies of C/T genotype and C allele were significantly higher in AS than controls after adjusting for age and gender (OR = 1.527, 95%CIs: 1.190–1.958; OR = 1.515, 95%CIs: 1.183–1.942, respectively). Dominant and co-dominant model of rs11624293 were predictive of AS susceptibility. In AS patients, the genotype of rs11624293 was significantly associated with BASFI scores in those with low disease activity (BASDAI < 4, p = 0.007). Conclusions The results of our study suggest that rs11624293 polymorphism of GPR65 gene is associated with the susceptibility and severity of AS in Chinese Han population. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is regarded as a persistent respiratory symptom, mainly caused by cigarette smoking. Recent data have suggested that some miRNAs are involved in the pathogenesis of COPD. Here, we found that miR-195 was significantly upregulated in the lung tissues of patients with COPD compared to in never smokers. miR-195 expression was also upregulated in cigarette smoke (CS)-exposed mice. Lentivirus-mediated knockdown of miR-195 alleviated CS-induced lung pathological changes and reduced inflammatory cell infiltration as well as production of interleukin-6 and tumor necrosis factor-α in bronchoalveolar lavage fluid. Mechanically, a positive correlation was found between miR-195 and phosphorylation of Akt in lung tissues of COPD patients. PHLPP2 was confirmed as a direct downstream target of miR-195 and negative regulator of miR-195 expression. Inhibition of PHLPP2 enhanced Akt phosphorylation and increased interleukin-6 and tumor necrosis factor-α production in BEAS-2B cells, resembling the effects of miR-195 overexpression. Collectively, our data indicate that miR-195 has a pathogenetic role in CS-induced COPD and regulates Akt signaling by suppressing PHLPP2 expression. miR-195 may be an effective therapeutic target in COPD. [ABSTRACT FROM AUTHOR]

For h-periodic coefficients and any integer k>2 it is well known that the eigenvalues of some self-adjoint complex boundary condition on the interval [ a , a + h ] are the same as the periodic eigenvalues on the interval [ a , a + kh ] . For each k we identify explicitly which of the uncountable number of complex conditions generates these periodic eigenvalues. In addition, we prove an analogous result for semi-periodic eigenvalues. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) have started to garner more interest as novel antimicrobial agents. The scorpion venom peptide ctry2459 was modified to CT-K3K7 by lysine substitutions at the 3rd and 7th positions to increase the cationic properties. We discovered that the modified peptides CT-K3K7 had improved antibacterial activity, higher thermal stability, as well as lower hemolytic activity. It can kill S. aureus and P. aeruginosa rapidly, and reduce the production of biofilm and live bacterial residues in biofilm in vitro. CT-K3K7 has also been demonstrated to decrease bacterial counts, abscess area, and inflammatory cell infiltration in the mouse subcutaneous abscess models that were duplicated by S. aureus and P. aeruginosa. CT-K3K7 has difficulty in inducing S. aureus and P. aeruginosa to develop drug resistance, which may be related to the bactericidal properties. CT-K3K7 increases cationic properties by lysine substitutions can increase the electrostatic force between the peptides and the bacterial surface, which can lead to an increase in bacterial membrane permeability and DNA binding. In conclusion, the modified peptide CT-K3K7 enhances the antimicrobial activity and can be a novel antimicrobial agent candidate for the treatment of infections by S. aureus and P. aeruginosa. [Display omitted] • The peptide CT-K3K7, modified by a lysine substitution had a stronger bactericidal effect. • CT-K3K7 could eliminate Staphylococcus aureus and Pseudomonas aeruginosa in vitro, and reduce the production of biofilm. • CT-K3K7 has been proven to have a bactericidal effect on the subcutaneous abscess model in mice. • The bactericidal mechanism of CT-K3K7 can destroy bacterial membranes and bind to the DNA through electrostatic force. [ABSTRACT FROM AUTHOR]

[Display omitted] • A mild method was developed to prepare the amine-functionalized cellulose aerogel. • The aerogel retains large specific surface area and low crystallinity. • Excessive graft density hinders urea adsorption. • Grafted amino or silicone hydroxy groups significantly promote urea adsorption. The development of efficient adsorbent materials to remove urea from dialysate is an effective way to solve the bottleneck limiting the development of a wearable artificial kidney. Three methods were used to fabricate amine-functionalized cellulose aerogels aiming to screen for excellent structures favorable for urea adsorption. The influence of APTES addition on the structure and adsorption performance of the adsorption materials was investigated. The kinetics and thermodynamics of urea adsorption were evaluated, and adsorption mechanisms were also discussed. Results indicate that the material prepared by the gentle method was still able to maintain a large specific surface area, large pore volume and low crystallinity. Amine-functionalized cellulose aerogels retain the original hydroxyl adsorption sites, and the amino or silanol hydroxyl as new adsorption active sites are also introduced. Furthermore, proper APTES graft density plays a critical role in the urea adsorption. The equilibrium adsorption capacity of urea on HA-N-NCA-10 is increased by 156%. [ABSTRACT FROM AUTHOR]

Background Current findings regarding serum Dickkopf-1 (DKK-1) concentration in ankylosing spondylitis (AS) have proven inconsistent. This meta-analysis was performed to provide a better understanding of serum DKK-1 and AS. Methods Online electronic databases were used to retrieve all relevant articles published before November 2017. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. Results 23 studies, containing 1348 AS patients and 909 healthy controls, were included in this meta-analysis. No significant difference in serum DKK-1 concentration was found between AS patients and healthy controls (pooled SMD = 0.488, 95%CI = −0.176 to 1.152, p  = 0.150). Subgroup analyses suggested that serum DKK-1 in patients with increased C-reactive protein (CRP) (CRP > 10 mg/L) and high modified Stroke AS Spine Score (mSASSS) (mSASSS > 30) were significantly lower than healthy controls. Serum DKK-1 was, however, increased in patients with normal CRP (CRP   ≤ 10 mg/L). Conclusion Although serum DKK-1 concentration was not significantly different in AS vs. healthy controls, it may be used as a biomarker of inflammation and radiographic damage in AS. [ABSTRACT FROM AUTHOR]

Objective Dickkopf-1 (DKK-1) is an endogenous inhibitor of canonical Wnt pathway that was implicated in the pathogenesis of rheumatoid arthritis (RA), but the serum levels of DKK-1 in RA were inconsistent among studies. Therefore, we conducted a meta-analysis to systematically evaluate the relationship between serum DKK-1 levels and RA. Methods PubMed, Web of Science and Cochrane Library were comprehensively retrieved till 1 January 2018 for pertinent studies. The pooled standard mean differences (SMDs) of serum DKK-1 levels were calculated according to the random effects model. Results Nine original studies containing 1305 RA patients and 504 healthy controls were included in the meta-analysis. The pooled SMD of serum DKK-1 between RA patients and healthy controls was 0.79 (95% CI = 0.11 to 1.48, Z  = 2.28 and P  = 0.023), indicating a significantly higher serum level of DKK-1 in RA patients. Conclusion Serum level of DKK-1 is elevated in patients with RA compared to healthy controls, suggesting an important role of DKK-1 in the pathogenesis and treatment of RA. [ABSTRACT FROM AUTHOR]

To improve the druggability of salinomycin, a 20-epi-amino-20-deoxysalinomycin derivatives library was synthesized with high efficacy from which a few salinomycin derivatives with high potency and selectivity were identified through comprehensive cytotoxicity assay, including a fluorine-19 magnetic resonance sensitive tool molecule. Using a K-ras cellular model, salinomycin and its derivatives showed different molecular mode of action from literature reports. These results would be valuable for developing salinomycin-based cancer therapy. [ABSTRACT FROM AUTHOR]

Objectives Various studies have researched the serum levels of leptin, adiponectin and resistin in patients with ankylosing spondylitis (AS), but the results were inconclusive. The purpose of this study was to systematically evaluate the correlations between serum levels of these adipokines and AS. Methods Electronic databases were retrieved to search relevant publications. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. Cochrane Q test and I 2 statistic were used to test heterogeneity. Subgroup analysis and meta-regression were applied to assess possible sources of heterogeneity. Results A total of sixteen articles were included. Meta-analysis results indicated no statistical differences between AS patients and normal controls in serum leptin and adiponectin levels (leptin, SMD = 0.829, 95% CI = − 0.116 to 1.774, p = 0.085; adiponectin, SMD = 0.460, 95% CI = − 0.004 to 0.924, p = 0.052). However, AS patients had higher serum resistin levels than controls (SMD = 1.413, 95% CI = 0.294 to 2.531, p = 0.013). Subgroup analyses suggested that Asian and African AS patients as well as patients aged < 40 years had higher serum leptin and resistin levels when compared to controls. Serum adiponectin levels were higher in AS patients compared to controls in subgroup of age ≥ 40, and serum resistin levels in subgroup of BMI ≥ 25. Measurement method was a source of heterogeneity for resistin. Publication bias was not observed and the robustness of study results was confirmed by sensitivity analysis. Conclusion Serum resistin, but not leptin or adiponectin levels may be closely associated with the development of AS. [ABSTRACT FROM AUTHOR]

IL-22 provides a new insight into the mechanisms of autoimmunity, and copy number variations (CNVs) are associated with autoimmune diseases. This study aims to explore the association of IL-22 gene CNVs with ankylosing spondylitis (AS) susceptibility. The copy numbers of IL-22 gene (2 fragments: IL-22_1, IL-22_2) were examined by AccuCopy™ methods in a cohort of 649 AS patients and 628 controls. Association of IL-22 CNVs and AS susceptibility was analyzed, and AS risk was estimated by Odds Ratio (ORs) and 95% confidence intervals (CIs), and the Benjamini-Hochberg method was applied to regulate the false discovery rate (FDR). We found one copy of IL-22 gene was significantly associated with AS [OR = 0.345, 95%CI (0.144, 0.827), P = 0.013, P FDR = 0.026] in the IL-22_2 fragment, and this association still exist after adjustment of age and sex [OR = 0.344, 95%CI (0.143, 0.825), P = 0.017, P FDR = 0.034]. In the stratification analysis by gender, the statistical difference was detected in males in the IL-22_2 fragment [OR = 0.306, 95%CI (0.121, 0.778), P = 0.009, P FDR = 0.018; adjusted OR = 0.306, 95%CI (0.120, 0.777), P = 0.013, P FDR = 0.026]. We suggest that IL-22 CNVs are associated with AS and that lower copy number might be a protective factor for AS, especially in male patients. [ABSTRACT FROM AUTHOR]

Intact somatic embryos were obtained from an elite maize inbred line Y423, bred in our laboratory. Using 13-day immature embryos after self-pollination as explants, and after 4–5 times subculture, a large number of somatic embryos were detected on the surface of the embryonic calli on the medium. The intact somatic embryos were transferred into the differential medium, where the plantlets regenerated with shoots and roots forming simultaneously. Histological analysis and scanning electron micrographs confirmed the different developmental stages of somatic embryogenesis, including globular-shaped embryo, pear-shaped embryo, scutiform embryo, and mature embryo. cDNA-amplified fragment length polymorphism (cDNA-AFLP) was used for comparative transcript profiling between embryogenic and non-embryogenic calli of a new elite maize inbred line Y423 during somatic embryogenesis. Differentially expressed genes were cloned and sequenced. Gene Ontology analysis of 117 candidate genes indicated their involvement in cellular component, biological process and molecular function. Nine of the candidate genes were selected. The changes in their expression levels during embryo induction and regeneration were analyzed in detail using quantitative real-time PCR. Two full-length cDNA sequences, encoding ZmSUF4 (suppressor of fir 4-like protein) and ZmDRP3A (dynamin-related protein), were cloned successfully from intact somatic embryos of the elite inbred maize line Y423. Here, a procedure for maize plant regeneration from somatic embryos is described. Additionally, the possible roles of some of these genes during the somatic embryogenesis has been discussed. This study is a systematic analysis of the cellular and molecular mechanism during the formation of intact somatic embryos in maize. [ABSTRACT FROM AUTHOR]