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A Zn(II) coordination polymer, [Zn3(4,4′-BMIBP)3(SIP)2] n (1) (4,4′-BMIBP = 4,4′-bis(2-methyl-imidazolyl)biphenyl, H3SIP = 5-sulfoisophthalic acid) was hydrothermally synthesized and structurally characterized. Complex 1 has a (3,4)-connected binodal four-fold three-dimensional topology with a point symbol of {4·62·82·10}2{4·62}2{64·102}. It shows strong fluorescence emission in the solid state and efficient photocatalytic performances to degrade methylene blue (MB) under UV irradiation, the degradation of MB reaching 88% after 50 min.

In the present study, a magnetic adsorbent, rhein-coated magnetic Fe3O4 nanoparticle (RMNP), for Pb2+ and Mg2+ had been developed, and adsorption mechanism was studied via low-field NMR. RMNP was characterized by TEM, FTIR, and XRD. RMNP could adsorb and remove Pb2+ and Mg2+ from water and was successfully applied to remove Pb2+ and Mg2+ from wastewater, with satisfactory recovery rates and high adsorption capacities. The calculated maximum adsorption capacity for Mg2+ and Pb2+ was approximately 69.3 and 64.9 mg g−1 of RMNP, respectively, which was better than some results reported. Low-field NMR results showed that Pb2+ or Mg2+ enhanced the T2 relaxation time of RMNP, which suggested that RMNP selectively coordinated with Pb2+ or Mg2+ and led to the aggregation of RMNP, furthermore removal of Pb2+ or Mg2+ from water. The standard curves for △T2-cation concentration exhibited good line correlation. The linear ranges were from 4.2 × 10−6 to 2.0 × 10−4 mol L−1 for Pb2+ and from 5.0 × 10−6 mol L−1 to 1.0 × 10−4 mol L−1 for Mg2+, respectively. The limits of detection were 1.4 × 10−6 mol L−1 for Pb2+ and 2.1 × 10−6 mol L−1 for Mg2+, respectively. In short, low-field NMR could clearly display the interaction between RMNP and Pb2+ or Mg2+, even be used to detect Pb2+ or Mg2+ in suitable condition. Besides, this method could be expanded to study the interaction between other magnetic adsorbents and analytes.

Leishmaniasis is a prevalent cause of death and animal morbidity in underdeveloped countries of endemic area. However, there is few vaccine and effective drugs. Antimicrobial peptides are involved in the innate immune response in many organisms and are being developed as novel drugs against parasitic infections. In the present study, we synthesized a 5-amino acid peptide REDLK, which mutated the C-terminus of Pseudomonas exotoxin, to identify its effect on the Leishmania tarentolae. Promastigotes were incubated with different concentration of REDLK peptide, and the viability of parasite was assessed using MTT and Trypan blue dye. Morphologic damage of Leishmania was analyzed by light and electron microscopy. Cellular apoptosis was observed using the annexin V-FITC/PI apoptosis detection kit, mitochondrial membrane potential assay kit and flow cytometry. Our results showed that Leishmania tarentolae was susceptible to REDLK in a dose-dependent manner, disrupt the surface membrane integrity and caused parasite apoptosis. In our study, we demonstrated the leishmanicidal activity of an antimicrobial peptide REDLK from Pseudomonas aeruginosa against Leishmania tarentolae in vitro and present a foundation for further research of anti-leishmanial drugs.

A fluorescent probe based on isorhamnetin (Iso)-cyclodextrin (CD) inclusion for detecting Cu2+ was synthesized. A major fluorescence emission peak at 542 nm was observed for isorhamnetin (Iso) in buffer solution (pH 7.40) when the excitation wavelength was 390 nm. It was surprisingly found that (2-hydroxypropyl)-β-cyclodextrin (β-CD) could enhance the fluorescence intensity of Iso, and the major fluorescence peak was shifted to 557 nm. UV-vis spectrum showed that the Iso-β-CD system was formed by hydrogen bond and hydrophobic interaction. And the fluorescence intensity of Iso-β-CD system was stronger and more stable compared with Iso. Further study indicated that Iso-β-CD system had good selectivity and sensitivity toward Cu2+. When Cu2+ was added, the fluorescent emission intensity of Iso-β-CD system was quenched, while other metal ions could not bring about obvious change, which meant that the Iso-β-CD system had good selectivity toward Cu2+. The fluorescence titration spectra indicated that the concentration of Cu2+ was inversely proportional to fluorescence intensity, and fluorescence emission intensity was linearly correlated with the concentration of Cu2+ in the range of 0.05–6.0 μM. The calibration equation was y = −11.66x + 781.13 (R2 = 0.996), with a limit of detection of 0.017 μM (S/N = 3). The possible reaction mechanism was studied by UV-vis spectroscopy and Job's plot method. The results indicated that Cu2+ could combine with Iso-β-CD system. The stoichiometric ratio for the complex of Iso and Cu2+ was 2:1. The formation of Iso-β-CD-Cu(II) complex led to the extension of the conjugated system and the intramolecular charge transfer (ICT) took place. Therefore, fluorescence of Iso-β-CD system was quenched. At last, the probe was successfully applied to determination of Cu2+ in water samples, vegetables and fruits with good recoveries, and the results coincided with those obtained by ICP-AES or AAS methods.

(13)C Magnetic resonance imaging of hyperpolarized (HP) (13)C-enriched bicarbonate (H(13)CO(3)(−)) and carbon dioxide ((13)CO(2)) is a novel and sensitive technique for tissue pH mapping in vivo. Administration of the HP physiological buffer pair is attractive, but poor polarization and the short T(1) of (13)C-enriched inorganic bicarbonate salts are major drawbacks for this approach. Here, we report a new class of mixed anhydrides for esterase-catalyzed production of highly polarized (13)CO(2) and H(13)CO(3)(−) in tissue. A series of precursors with different alkoxy and acyl group were synthesized and tested for chemical stability and T(1). (13)C-enriched ethyl acetyl carbonate ((13)C-EAC) was found to be the most suitable candidate due to the relatively long T(1) and good chemical stability. Our results showed that (13)C-EAC can be efficiently and rapidly polarized using BDPA. HP (13)C-EAC was rapidly hydrolyzed by esterase to (13)C-enriched monoacetyl carbonate ((13)C-MAC), which then decomposed to HP (13)CO(2). Equilibrium between the newly produced (13)CO(2) and H(13)CO(3)(−) was quickly established by carbonic anhydrase, producing a physiological buffer pair with (13)C NMR signals that can be quantified for pH measurements. Finally, in vivo tissue pH measurements using HP (13)C-EAC was successfully demonstrated in the liver of healthy rats. These results suggest that HP (13)C-EAC is a novel imaging probe for in vivo pH measurements.

A novel symmetrical macrocyclic phthalate hexaester (1) and a known macrocyclic phthalate tetraester (2) were isolated during a natural product-exploring program on the cyanobacterium Moorea producens. Their structures were elucidated based on spectroscopic data, including nuclear magnetic resonance and high-resolution mass spectra. In the antibacterial activity test, compounds 1 and 2 showed no bioactivity at the concentrations tested.

An amendment to this paper has been published and can be accessed via the original article.

Background Human hair follicle mesenchymal stem cells (hHFMSCs) isolated from hair follicles possess multilineage differentiation potential. OCT4 is a gene critically associated with pluripotency properties. The cell morphology and adhesion of hHFMSCs significantly changed after transduction of OCT4 and two subpopulations emerged, including adherent cells and floating cell. Floating cells cultured in hematopoietic induction medium and stimulated with erythropoetic growth factors could transdifferentiate into mature erythrocytes, whereas adherent cells formed negligible hematopoietic colonies. The aim of this study was to reveal the role of cell morphology and adhesion on erythropoiesis induced by OCT4 in hHFMSCs and to characterize the molecular mechanisms involved. Methods Floating cell was separated from adherent cell by centrifugation of the upper medium during cell culture. Cell size was observed through flow cytometry and cell adhesion was tested by disassociation and adhesion assays. RNA sequencing was performed to detect genome-wide transcriptomes and identify differentially expressed genes. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by differentially expressed genes. The expression of tight junction core members was verified by qPCR and Western blot. A regulatory network was constructed to figure out the relationship between cell adhesin, cytoskeleton, pluripotency, and hematopoiesis. Results The overexpression of OCT4 influenced the morphology and adhesion of hHFMSCs. Transcripts in floating cells and adherent cells are quite different. Data analysis showed that upregulated genes in floating cells were mainly related to pluripotency, germ layer development (including hematopoiesis lineage development), and downregulated genes were mainly related to cell adhesion, cell junctions, and the cytoskeleton. Most molecules of the tight junction (TJ) pathway were downregulated and molecular homeostasis of the TJ was disturbed, as CLDNs were disrupted, and JAMs and TJPs were upregulated. The dynamic expression of cell adhesion-related gene E-cadherin and cytoskeleton-related gene ACTN2 might cause different morphology and adhesion. Finally, a regulatory network centered to OCT4 was constructed, which elucidated that he TJ pathway critically bridges pluripotency and hematopoiesis in a TJP1-dependent way. Conclusions Regulations of cell morphology and adhesion via the TJ pathway conducted by OCT4 might modulate hematopoiesis in hHFMSCs, thus developing potential mechanism of erythropoiesis in vitro.

Particle based simulations are widely used in computer graphics. However, few methods use active control for fluid surface. Thus we present a new controllable method based on the spring force model, which provides active control for the disturbance of the fluid surface. This method modifies the spatial distribution of the particles to generate disturbance. To make it controllable, we design a disturbance equation, using the relationship between the macrostate of fluid and the microscopic particles in the Boltzmann’s Entropic Equation. Moreover, we also propose multiple optimizations in order to improve appearance of fluid surface. The correction of fluid splash first detects the target particles by a hybrid method, then adjusts the spring force that acts on these particles. The spring force attenuation model uses a sigmoid function to represent the attenuation of particles at different depths. Experimental results show that our method generates the expected disturbance details. The optimizations enhance the realism of the disturbance simulation.

Since public opinion from social media has a growing impact and supervision on the trial, risk assessment on public opinion is increasingly important in the refinement of trial management. However, due to insufficient historical training data, lack of high accuracy in risk prediction and so on, existing methods cannot be effectively applied to risk assessment on public opinion. To address this, we propose a fine-grained risk assessment framework on public opinion with fuzzy numbers. Firstly, we establish a multilayer indicator model for assessing the Risk of Public Opinion (POR), in the model, the indicators are defined and allocated priorities based on AHP. Secondly, we design a public opinion analysis module for indicator evaluation, which includes analysis in public opinion sentiment, in hot search and in social media coverage. Specially, the public opinion sentiment is calculated by aggregating sentiments of topic clusters, which is accurate and reasonable. Finally, the fuzzy number similarity is employed to determine the level of POR in the nine-levels risk system. Experimental results validate the efficiency of our framework when assessing the POR.

Background: Human hair follicle mesenchymal stem cells (hHFMSCs) isolated from hair follicles possess multilineage differentiation potential. OCT4 is a gene critically associated with pluripotency properties. The cell morphology and adhesion of hHFMSCs significantly changed after transduction of OCT4 and two subpopulations emerged, including adherent cells and floating cell. Floating cells cultured in hematopoietic induction medium and stimulated with erythropoetic growth factors could transdifferentiate into mature erythrocytes, whereas adherent cells formed negligible hematopoietic colonies. The aim of this study was to reveal the role of cell morphology and adhesion on erythropoiesis induced by OCT4 in hHFMSCs and to characterize the molecular mechanisms involved.Methods: Floating cell were separated from adherent cell by centrifugation of the upper medium during cell culture. Cell size was observed through flow cytometry and cell adhesion was tested by disassociation and adhesion assays. RNA sequencing was performed to detect genome-wide transcriptomes and identify differentially expressed genes. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by differentially expressed genes. The expression of tight junction core members was verified by qPCR and Western blot.Results: The overexpression of OCT4 influenced the morphology and adhesion of hHFMSCs. Transcripts in floating cells and adherent cells are quite different. Data analysis showed that upregulated genes in floating cells were mainly related to the pluripotency, germ layer development (including hematopoiesis lineage development), and downregulated genes were mainly related to cell adhesion, cell junctions and the cytoskeleton. Most molecules of the tight junction (TJ) pathway were downregulated and molecular homeostasis of the TJ was disturbed, as CLDNs were disrupted, and JAMs and TJPs were upregulated. The dynamic expression of cell adhesion-related gene E-cadherin and cytoskeleton-related gene ACTN2 might cause different morphology and adhesion. Finally, a regulatory network centered to OCT4 was constructed, which elucidated the TJ pathway critically bridges pluripotency and hematopoiesis in a TJP1-dependent way.Conclusions: Regulations of cell morphology and adhesion via the TJ pathway conducted by OCT4 might modulate hematopoiesis in hHFMSCs, thus developing potential mechanism of erythropoiesis in vitro.

In the present study, a magnetic adsorbent, rhein-coated magnetic Fe

Alterations in the microbiome are associated with the development of gastric cancer. Our study aimed to identify dysbiotic features in early gastric cancer (EC). The gastric microbiome was assessed in EC (n = 30), advanced gastric cancer (AC) (n = 30), and chronic gastritis (CG) (n = 60). The results demonstrated significant differences in the microbial profile and composition between EC and AC, suggesting alterations associated with gastric cancer progression. Linear discriminant analysis (LDA) effect size (LEfSe) analyses identified 32 bacterial genera that were associated with EC. Functional analyses of the gastric microbiome showed that the production of urease and synthesis of bacterial flagella were weakened in EC, while the glycolysis of fructose and hydrolysis of glycosides were enhanced. A classifier based on a random forest (RF) machine learning algorithm identified a microbial signature that distinguished EC from CG or AC with high accuracy. The correct identification of the signature was further validated in independent cohorts. This signature enriched of bacteria with varied abundance, high degree of bacterial interactions and carcinogenic potentials. Constrained principal coordinate analyses revealed that the presence of Helicobacter pylori and the cagA and vacA virulence genotypes influenced the structure of the gastric microbiome. To determine the impacts of host genetic variations on the gastric microbiome, six previously reported single nucleotide polymorphisms (SNPs) were examined. The minor allele of MUC1 rs4072037 was associated with an increased abundance of Ochrobactrum. The gastric microbiome altered in EC, which might be attributed in part to host genetic variations, H. pylori infection, bacterial virulence and environmental adaptations. The identified microbial signature could serve as biomarkers for clinical assessment of gastric cancer risk in high-risk patients.

Additional file 1: Fig. S1. Comparisons of the transcripts. (a) Correlation coefficient between samples displayed in a heatmap. The closer the correlation coefficient is to 1, the higher the sample similarity is. (b) Hierarchical clustering of correlation of the three groups of cells. The closer the sample clustering distance is, the higher the sample similarity is.

In this work, a novel fluorescent sensor (quercetin-Pluronic-F127 nano-micelles) was prepared by the facile self-assembly method with natural quercetin (Qc) and Pluronic-F127 (F127). Qc-F127 nano-micelles were characterized by TEM which indicated that Qc have successfully entered into the amphiphilic micelle. The nano micelles with sizes of 25 to 40 nm showed a strong green fluorescence (FL). The sensor exhibits high sensitivity and selectivity towards Cu2+ with a linear range of 5 × 10−8–4 × 10−6 mol L−1, the detection limit of 1 × 10−8 mol L −1. Moreover, the Qc-F127 nano-micelles can be used to detect Cu2+ in vitro due to their good biocompatibility. Besides Cu2+ sensing, when Cysteine (Cys) were added, the FL intensity of Qc-F127-Cu(II) system could be restored due to the chelation interactions between Cu2+ ions and the sulfydryl and amino groups of Cys. So, Qc-F127-Cu(II) system can used to detect Cys, and the linear range and the limit of detection of the Qc-F127-Cu2+ system were 3 × 10−7–3.5 × 10−5 mol L−1 and 6 × 10−8 mol L −1. Moreover, Qc-F127-Cu(II) has been used for imaging of Cys in cells, which demonstrates its values for potential application in biological systems.

Environmentally friendly probe materials for detecting copper ions were studied in this research. Fluorescent emission of quercetin (Q) was observed in the buffer solution (pH = 7.40), and (2-hydroxypropyl)-β-cyclodextrin (CD) could enhance the fluorescence intensity of Q. The UV/Vis spectrum showed that the Q-CD system was formed. After adding copper ions into the Q-CD system, the fluorescent emission intensity of Q-CD system generated quenching, and other metal ions could not bring change, which meant the Q-CD system showed good selectivity to copper ions. The fluorescence titration spectra showed that the concentration of copper ions was inversely proportional to fluorescence intensity, and gave a good linear change in fluorescence emission intensity in response to the concentration of copper ions ranging from 5.0 × 10−8 to 8.3 × 10−6 mol L−1. The calibration curve of the relationship between the intensity and copper ions concentration was y = −9.24x + 844.51 (R2 = 0.997). The detection limit of copper ions was measured to be 2.3 × 10−8 mol L−1. The probable mechanism was studied by UV/Vis spectrum and Job's plot method. The results indicated that Q-CD-Cu(II) complex was formed and intramolecular charge transfer (ICT) took place. At last, the probe was successfully applied for determination of copper ions in water bodies, vegetables and fruits with good recovery. The study showed that Q-CD system could detect copper ions as a fluorescent probe with high selectivity, sensitivity and larger linearity range.

In this paper, we develop quercetin-coated Fe3O4 nanoparticles (QMNPS) as a sensor for the detection and removal of Pb2+ and Cu2+ based on low-field NMR. QMNPS were characterized by TEM, FTIR and XRD. The NMR sensor showed high selectivity toward Pb2+ or Cu2+. The standard curves for ΔT2-ion concentration showed good correlations, i.e., R2 = 0.9912 for Pb2+ and 0.9983 for Cu2+; the linear ranges and the limits of detection were 4.8 × 10−6–1 × 10−4 mol L−1 and 1.6 × 10−6 mol L−1 for Pb2+, and 5.0 × 10−6–1 × 10−4 mol L−1 and 2.0 × 10−6 mol L−1 for Cu2+, respectively. The calculated maximum adsorption capacity was about 71 mg for Cu2+ and 68 mg for Pb2+ per gram of QMMP, which was superior to the results of some previous reports. The detection and removal of Pb2+ or Cu2+ was based on the coordination reaction between the NMR sensor of QMNPs and Pb2+ or Cu2+, which led to the aggregation of QMNPs. As a result, the proposed NMR sensor was successfully applied for the determination and removal of Pb2+ and Cu2+ in contaminated water and urine samples with excellent recoveries and high adsorbent capacities.

Chemical analysis of the hydrophilic fraction from marine cyanobacterium Moorea producens extracts led to the isolation of five new indole derivatives (1-5). So far, 2-formyl-4,5,6,7-tetrahydroindole has been reported only for 6 from the nature, consequently compounds 1-5 were the second representatives of this class. Cytotoxicity, diatom growth inhibition, and antibacterial activity tests for compounds 1-5 showed no bioactivity at the concentration tested.

A natural isorhamnetin-based fluorescent sensor for highly sensitive and selective detection of copper ions had been studied. The fluorescent sensor isorhamnetin (Iso) after binding to Cu 2+ ions in pH 7.40 buffer solution generated quenching in fluorescent emission intensity. The binding constant value was obtained 1.79 × 10 6 . The sensor Iso can be applied to the quantification of Cu 2+ ion with a linear range of 1.0 × 10 −8 –1.9 × 10 −6 mol L −1 , the detection limit of 4.0 × 10 −9 mol L −1 , and the reproducibility of the sensor is good. The sensor showed high selectivity toward Cu 2+ . As a result, the isorhamnetin fluorescent sensor was successfully applied for determination of Cu 2+ in rivers, lakes, vegetables and fruits with good recovery.

The block X is an integrated upstream and downstream development, comprising the development of oil fields and the construction and operation of pipelines and a refinery [1]. The upstream development consists of 73 fault blocks scattered in nine oil fields, in which four blocks are already in development, and the others will be under full development in the near future. The development strategies need to meet the strategic goal of maximizing the length of the stable production plateau for three production scenarios (low, base, and high) while fulfilling the objectives of maximizing the integrated economic value (NPV), fast recovery of the investment, and minimizing risks. To model the development strategy [2, 3], first, a single well economic case for each development block is created, and total production volume at economic limit is generated. It is then followed by the screening process to filter out the uneconomical blocks which do not meet the hurdle rate for the single well economic limit production volume. The economics results for each block passing the screening process are then brought into Merak Capital planning as the base for the optimization. The optimization is set up to generate three strategies which determine the onstream time options for each of the block development to meet the three strategic production plateau goals and fulfill the objectives. The business rules modeled in Merak Capital Planning [4−6] represent the dependency between the onstream time and the commissioning date of the export pipelines, the completion time of the surface facilities, the size and quality of the blocks, and the distance of the block to CPF, as well as the processing capacity of the refinery. The optimization is done by using both the Lindo and Genetic Algorithm methods. For each strategy, multiple options are generated from the optimization. Based on the optimization outcomes, full life cycle economic evaluation is performed to assess integrated upstream–downstream economic value [7] of the multiple development options for each strategy. Finally, the optimal development option for each strategy to meet the company’s strategic goals is determined based on the integrated economic results of the optimized development options [8−10].

Metabolic imaging by nuclear methods is widely used to access ischemic myocardium but provide limited information about individual enzyme-catalyzed reactions. 13 C hyperpolarization methods are sensitive to flux in specific key enzymes such as lactate dehydrogenase and pyruvate dehydrogenase. We tested the hypothesis that LDH flux is increased while PDH flux is abolished in low-flow ischemia. Metabolism of HP [1- 13 C]pyruvate was studied in four groups: (1) normal perfusion pressure (NPP), 100 cm H 2 O; (2) NPP with epinephrine; (3) low-perfusion pressure (LPP), 25 cm H 2 O; (4) LPP with epinephrine. Hearts excised from male Sprague-Dawley rats were perfused (37°C) at an initial pressure of 100 cm H 2 O using standard Langendorff method with Krebs-Henseleit buffer containing 0.75% bovine serum albumin, 0.4 mM non-labeled free fatty acid, 5.5 mM [U- 13 C]glucose, 1 mM [3- 13 C]pyruvate, 0.1 mM [3- 13 C]lactate. Perfusion pressure was reduced to 25 cm H 2 O after 30 min of perfusion for ischemia group and epinephrine added at 50 th min of perfusion. HP [1- 13 C]pyruvate was injected to heart and subsequently, 13 C NMR spectra were acquired. The freeze clamped heart tissues were extracted with perchloric acid and analyzed by high-resolution 1 H and 13 C NMR (14.1 T). The 31 P NMR spectroscopy confirmed significant myocardial ischemia under LPP conditions, demonstrated by a marked increase in the [Pi]/[ATP] ratio. Surprisingly, increased LDH flux was observed in the ischemic hearts (+18.4%) while the metabolism of HP [1- 13 C]pyruvate by PDH remained unchanged as indicated by bicarbonate production. To investigate the oxidative capacity of mitochondria, epinephrine was used to stimulate hearts. As anticipated, epinephrine increased heart rate (+23%) and coronary flow (+11%) under NPP. Epinephrine increased heart rate (-60%) but did not alter coronary flow under LPP. We found that epinephrine had no effect on the rate of bicarbonate production under LPP. The study demonstrated that the conversion of pyruvate to lactate increased in ischemic hearts but the degree of pyruvate oxidation was not affected by the low-flow ischemia. Adrenergic stimulation did not increase PDH flux in these ischemic hearts. Translation to human is likely to provide new data from low-flow myocardium.

Leishmaniasis, caused by the intracellular protozoan parasite Leishmania, remains an important neglected tropical infectious disease. Infection may be lethal if untreated. Currently, the available drugs for the disease are limited by high toxicity and drug resistance. There is an urgent need to develop novel anti-leishmanial strategies. Antimicrobial peptides (AMPs) have been described as the first-line immune defense against pathogenic microbes and are being developed as emerging anti-parasitic therapies. In the present study, we showed the anti-leishmanial activity of the synthetic 4-amino acid peptide lysine, aspartic acid, glutamic acid, and leucine (KDEL), the endoplasmic reticulum retention sequence, against Leishmania tarentolae promastigote and amastigote. Different concentrations of KDEL peptides were incubated with promastigotes, MTT viability assay, and promastigote assay were carried out. Macrophages infected with GFP-transfected L. tarentolae promastigotes were incubated with KDEL peptides, and the anti-amastigote activity of the KDEL peptides was measured by fluorescence microscopy. The damage of L. tarentolae was observed by light microscopy and electron microscopy. The cell apoptosis was analyzed using the Annexin V-FITC/PI apoptosis detection kit and mitochondrial membrane potential assay kit and by flow cytometry. Results showed that L. tarentolae was susceptible to KDEL peptides in a dose-dependent manner, and KDEL peptides disrupted the surface membrane integrity and caused cell apoptosis. In our study, we found for the first time an AMP KDEL from Pseudomonas aeruginosa and proved its significant therapeutic potential as a novel anti-leishmanial drug.

Background: Gastric microbiome has been well characterized gastric cancer. Alterations associated with gastric cancer have been identified. However, little is known regarding the dysbiotic features in early gastric cancer. Methods: Gastric microbiome was assessed in early gastric cancer (n=30), advanced gastric cancer (n=30) and chronic gastritis (n=60). Random forest machine learning algorithm was used to identify signatures capable of predicting early gastric cancer. In addition, influence of Helicobacter pylori virulence and cancer-associated single nucleotide polymorphisms in PRKAA1, PTGER4, PSCA, MUC1 and UNC5CL on gastric microbiome was determined. Findings: There were significant differences in the microbial profile and composition between early and advanced gastric cancer, suggesting alterations associated with cancer progression. Compared with chronic gastritis, 32 bacteria genera were found to be enriched or depleted in early gastric cancer. Production of urease and synthesis of bacteria flagellum were decreased, while glycolysis of fructose and hydrolysis of glycosides were enhanced. The correlation network became simplified and fragmented. A microbial signature enclosing 24 bacteria was identified, which could distinguish early gastric cancer from chronic gastritis with an AUC value of 0.97. H. pylori had impacts on gastric microbiome. The minor allele of MUC1 SNP rs4072037 was associated with increased abundance of Ochrobactrum. Interpretation: Gastric microbiome showed distinct features in early gastric cancer. The identified microbial signature could be used as biomarkers for predicting early gastric cancer. Funding: National natural Science Foundation of China (31870777, 81602144). Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: This study was approved by the Research Ethnics Committee of Qingdao Municipal Hospital, China. Informed written consent was obtained from all participants.

Testing applications with GUI is one of the most tedious tasks in software development. Test automation alleviates this burden by executing scripts that simulate how users interact with GUI. However, in practice efforts spent on developing GUI test automation scripts can be wasteful when the application evolves and modifies GUI components that are referenced by the scripts. In this paper, we propose a new test script repair framework to address this problem. The framework of our method consists of three main modules. Firstly, the script processing module calculates a similarity matrix of each script pair. Secondly, the code analysis module maintains an object repair map which is used to store repair operations. Finally, the script update module applies the map to the scripts under repair. The repair rate of our method keeps increasing with more test script pairs provided and it could be more than 95%. Experiments also show that our method is better than the tool for scrip maintaining within QTP not only in repair rate but also in time consuming.

A novel acylhydrazone coumarin fluorescent chemosensor C4 for detection of Ni2+ was designed and synthesized. The experimental results revealed a low detection limit of 2.1 × 10−11 M with high selectivity and excellent sensitivity towards Ni2+. C4 showed a good linear relationship with the concentration of Ni2+ from 1.3 × 10−6 to 1.6 μM. Moreover, a stable complex was formed between C4 and with Ni2+ and the binding ratio was proved to be 2: 1 by Job’s plot and mass spectrum. The sensing ability of C4 towards Ni2+ was attributed to parity-forbidden transition according to fluorescence titrations and DFT calculations. The detection of Ni2+ in water samples illustrated C4 could be successfully applied for the detection of Ni2+ in real environmental samples. What’s more, the fluorescence microscopy images of Hela cells demonstrated the high potential of the novel biosensor for the investigation of biological processes involving Ni2+, as well.

Mitochondrial dysfunction is considered to be an important component of many metabolic diseases yet there is no reliable imaging biomarker for monitoring mitochondrial damage in vivo. A large prior literature on inter-conversion of β-hydroxybutyrate (β-HB) and acetoacetate (AcAc) indicates that the process is mitochondrial and the ratio reflects specifically mitochondrial redox state. Therefore the conversion of [1,3-(13)C]AcAc to [1,3-(13)C]β-HB is expected to be sensitive to the abnormal redox state present in dysfunctional mitochondria. In this study, we examined conversion of hyperpolarized (HP) (13)C-acetoacetate (AcAc) to (13)C-β-hydroxybutyrate (β-HB) as a potential imaging biomarker for mitochondrial redox and dysfunction in perfused rat hearts. Conversion of HP AcAc to β-HB was investigated using (13)C magnetic resonance spectroscopy (MRS) in Langendorff-perfused rat hearts in four groups: control, global ischemic reperfusion, low-flow ischemic, and rotenone (mitochondrial complex-I inhibitor) treated hearts. We observed that more β-HB was produced from AcAc in ischemic hearts and the hearts exposed to complex I inhibitor, rotenone, compared to controls consistent with accumulation of excess mitochondrial NADH. The increase in β-HB, as detected by (13)C MRS, was validated by a direct measure of tissue β-HB by (1)H nuclear magnetic resonance (NMR) in tissue extracts. The redox ratio, NAD(+)/NADH, measured by enzyme assays of homogenized tissue, also paralleled production of β-HB from AcAc. Transmission electron microscopy of tissues provided direct evidence for abnormal mitochondrial structure in each ischemic tissue model. The results suggest that conversion of HP-AcAc to HP-β-HB detected by (13)C-MRS may serve as a useful diagnostic marker of mitochondrial redox and dysfunction in heart tissue in vivo.

A natural quercetin-based fluorescent sensor for highly sensitive and selective detection of copper ions has been studied. The quercetin fluorescent sensor after binding to Cu2+ ions in pH 7.40 buffered solution showed a quenching of fluorescence emission intensity. The binding constant value was obtained as 3.56 × 107. The sensor can be applied to the quantification of Cu2+ ions with a linear range of 2.0 × 10−7–3.0 × 10−6 mol L−1 and a detection limit of 1.0 × 10−7 mol L−1. The sensor showed high selectivity toward Cu2+. As a result, the proposed fluorescent sensor was successfully applied for determination of Cu2+ in water samples.

A new malyngamide (1) was isolated along with seven known compounds (2–8) from the marine cyanobacterium Moorea producens collected in Hawaii. Compound 1 represented the first reported malyngamide with a hydroxy moiety at C-7 of the characteristic fatty acid portion of the compound. Compound 1 showed cytotoxicity against L1210 cell line at an IC50 value of 2.9 mM and lethal toxicity against the shrimp Palaemon paucidens at a LD100 value of 33.3 mg/kg. The bioactivity of compound 1 was approximately 10–100 times weaker than those of isomalyngamides A and B (3, 4). These results indicated that the methoxy group at C-7 of the fatty acid section confers a degree of bioactivity in malyngamides.