Preliminary study on the short-term changes of pulmonary perfusion after a single balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Little is known about immediate responses of blood perfusion to the balloon pulmonary angioplasty (BPA) procedure. OBJECTIVES: To investigate the changes in pulmonary perfusion of balloon-dilated vessels and untreated vessels with before, immediately after a single BPA and at follow-up. DESIGN: Retrospective single-center cohort study. METHODS: Patients who had chronic thromboembolic pulmonary hypertension (CTEPH) and completed the pulmonary perfusion single photon emission computed tomography (SPECT) imaging before, immediately after BPA and at follow-up were included. We evaluated the perfusion defects of both-lung, BPA target (balloon dilated) and non-target (untreated) vessel segments according to Begic 3-point scale in each lung segment. RESULTS: Forty patients (40 BPA procedures) were included and were given next BPA after 89 (62-125) days. The hemodynamic parameters including mPAP, PVR, and RAP were significantly improved after a single BPA. Visual scoring results of pulmonary perfusion imaging in 40 BPAs showed the perfusion defect scores of target vessels reduced from 5.6 ± 2.6 to 4.2 ± 2.2 (p < 0.001) immediately after BPA, and then further diminished to 3.1 ± 1.9 (p < 0.001) at follow-up. While in the non-target vessels, the post-BPA perfusion defect scores did not change significantly (13.4 ± 4.7 versus 12.8 ± 4.6, p = 0.182), but tended to decrease at follow-up (12.2 ± 4.2). However, there were 17 BPAs of which the post-BPA perfusion defect scores of non-target vessels increased significantly (p < 0.001), but decreased at follow-up. CONCLUSION: In addition to improving the blood perfusion of target vessels, BPA also has a certain effect on the perfusion of some non-target vessels.

Improved Membrane Permeability via Hypervesiculation for In Situ Recovery of Lycopene in Escherichia coli.

Lycopene biosynthesis is frequently hampered by downstream processing hugely due to its inability to be secreted out from the producing chassis. Engineering cell factories can resolve this issue by secreting this hydrophobic compound. A highly permeable E. coli strain was developed for a better release rate of lycopene. Specifically, the heterologous mevalonate pathway and crtEBI genes from Corynebacterium glutamicum were overexpressed in Escherichia coli BL21 (DE3) for lycopene synthesis. To ensure in situ lycopene production, murein lipoprotein, lipoprotein NlpI, inner membrane permease protein, and membrane-anchored protein in TolA-TolQ-TolR were deleted for improved membrane permeability. The final strain, LYC-8, produced 438.44 ± 8.11 and 136.94 ± 1.94 mg/L of extracellular and intracellular lycopene in fed-batch fermentation. Both proteomics and lipidomics analyses of secreted outer membrane vesicles were perfect indicators of hypervesiculation. Changes in the ratio of saturated fatty acids, unsaturated fatty acids, and cyclopropane fatty acids coupled with the branching and acyl chain lengths altered the membrane fatty acid composition. This ensured membrane fluidity and permeability for in situ lycopene release. The combinatorial deletion of these genes altered the cellular morphology. The structural and morphological changes in cell shape, size, and length were associated with changes in the mechanical strength of the cell envelope. The enhanced lycopene production and secretion mediated by improved membrane permeability established a cell lysis-free system for an efficient releasing rate and downstream processing, demonstrating the importance of vesicle-associated membrane permeability in efficient lycopene production.

Engineering Escherichia coli BL21 (DE3) for high-yield production of germacrene A, a precursor of ß-elemene via combinatorial metabolic engineering strategies.

ß-elemene is one of the most commonly used antineoplastic drugs in cancer treatment. As a plant-derived natural chemical, biologically engineering microorganisms to produce germacrene A to be converted to ß-elemene harbors great expectations since chemical synthesis and plant isolation methods come with their production deficiencies. In this study, we report the design of an Escherichia coli cell factory for the de novo production of germacrene A to be converted to ß-elemene from a simple carbon source. A series of systematic approaches of engineering the isoprenoid and central carbon pathways, translational and protein engineering of the sesquiterpene synthase, and exporter engineering yielded high-efficient ß-elemene production. Specifically, deleting competing pathways in the central carbon pathway ensured the availability of acetyl-coA, pyruvate, and glyceraldehyde-3-phosphate for the isoprenoid pathways. Adopting lycopene color as a high throughput screening method, an optimized NSY305N was obtained via error-prone polymerase chain reaction mutagenesis. Further overexpression of key pathway enzymes, exporter genes, and translational engineering produced 1161.09 mg/L of ß-elemene in a shake flask. Finally, we detected the highest reported titer of 3.52 g/L of ß-elemene and 2.13 g/L germacrene A produced by an E. coli cell factory in a 4-L fed-batch fermentation. The systematic engineering reported here generally applies to microbial production of a broader range of chemicals. This illustrates that rewiring E. coli central metabolism is viable for producing acetyl-coA-derived and pyruvate-derived molecules cost-effectively.

Metabolic Engineering Mevalonate Pathway Mediated by RNA Scaffolds for Mevalonate and Isoprene Production in Escherichia coli.

Co-localizing biochemical processes is a great strategy when expressing the heterologous metabolic pathway for product biosynthesis. The RNA scaffold is a flexible and efficient synthetic compartmentalization method to co-localize the enzymes involved in the metabolic pathway by binding to the specific RNA, binding domains fused with the engineered enzymes. Herein, we designed two artificial RNA scaffold structures─0D RNA scaffolds and 2D RNA scaffolds─using the reported aptamers PP7 and BIV-Tat and the corresponding RNA-binding domains (RBDs). We verified the interaction of the RBD and RNA aptamer in vitro and in vivo. Then, we determined the efficiencies of these RNA scaffolds by co-localizing fluorescent proteins. We employed the RNA scaffolds combined with the enzyme fusion strategies to increase the metabolic flux involved in the enzymes of the mevalonate pathway for mevalonate and isoprene production. Compared with the no RNA scaffold strain, the mevalonate levels of the 0D RNA scaffolds and 2D RNA scaffolds increased by 84.1% (3.13 ± 0.03 g/L) and 76.5% (3.00 ± 0.09 g/L), respectively. We applied the 0D RNA scaffolds for increasing the isoprene production by localizing the enzymes involved in a heterologous multi-enzyme pathway. When applying the RNA scaffolds for co-localizing the enzymes mvaE and mvaS, the isoprene production reached to 609.3 ± 57.9 mg/L, increasing by 142% compared with the no RNA scaffold strain. Our results indicate that the RNA scaffold is a powerful tool for improving the efficiencies of the reaction process in the metabolic pathway.

Immobilization of D-allulose 3-epimerase into magnetic metal-organic framework nanoparticles for efficient biocatalysis.

D-allulose is a rare low-calorie sugar that has many fundamental biological functions. D-allulose 3-epimerase from Agrobacterium tumefaciens (AT-DAEase) catalyzes the conversion of D-fructose to D-allulose. The enzyme has attracted considerable attention because of its mild catalytic properties. However, the bioconversion efficiency and reusability of AT-DAEase limit its industrial application. Magnetic metal-organic frameworks (MOFs) have uniform pore sizes and large surface areas and can facilitate mass transport and enhance the capacity for enzyme immobilization. Here, we successfully encapsulated cobalt-type AT-DAEase into the cobalt-based magnetic MOF ZIF-67@Fe3O4 using a self-assembly strategy. We confirmed the immobilization of enzyme AT-DAEase and characterized the enzymatic properties of the MOF-immobilized AT-DAEase@ZIF-67@Fe3O4. The AT-DAEase@ZIF-67@Fe3O4 nanoparticles had higher catalytic activity (65.1 U mg-1) and bioconversion ratio (38.1%) than the free AT-DAEase. The optimal conditions for maximum enzyme activity of the AT-DAEase@ZIF-67@Fe3O4 nanoparticles were 55 °C and pH 8.0, which were significantly higher than those of the free AT-DAEase (50 °C and pH 7.5). The AT-DAEase@ZIF-67@Fe3O4 nanoparticles displayed significantly improved thermal stability and excellent recycling performance, with 80% retention of enzyme activity at a temperature range of 45-70 °C and > 45% of its initial activity after eight cycles of enzyme use. The AT-DAEase@ZIF-67@Fe3O4 nanoparticles have great potential for large-scale industrial preparation of D-allulose by immobilizing cobalt-type AT-DAEase into magnetic MOF ZIF-67@Fe3O4.

Improving the imaging diagnostic strategy for pulmonary artery masses based on 18F-FDG PET/CT integrated with CTPA.

OBJECTIVE: To evaluate the diagnostic accuracy of computed tomography pulmonary angiography (CTPA) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for pulmonary artery (PA) masses. METHODS: Of 2889 patients with PA filling defects of PA on CTPA, 79 consecutive patients suspicious for PA malignancy who subsequently underwent 18F-FDG PET/CT were enrolled. All masses were diagnosed on the basis of pathological findings or clinical imaging follow-up. For each mass, morphological CT signs, standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18F-FDG PET/CT were used as diagnostic markers. RESULTS: Expansive growth, irregular margin, invasion, CT contrast uptake, and wall eclipse sign were strongly associated with the malignant nature of masses. The coexistence of at least 5 CT signs perfectly identified malignant masses, whereas the detection of no more than 4 CT signs did not accurately discriminate between the natures of masses. Mean SUVmax, SUVmean, MTV, and TLG values were significantly higher in malignant masses compared to those in benign masses. The diagnostic accuracy of 18F-FDG PET/CT parameters (SUV, MTV, and TLG) was excellent in detecting malignant masses. Among patients with 3 or 4 pathological CT signs, SUVmax > 3.4 significantly increased the identification of malignancies. CONCLUSIONS: CTPA is a useful imaging modality for diagnosing PA masses, especially when at least 5 abnormal CT signs are identified. Similarly, 18F-FDG PET/CT accurately identified malignant masses and provided additional valuable information on diagnostic uncertainties after CTPA.

Ticagrelor reduces doxorubicin-induced pyroptosis of rat cardiomyocytes by targeting GSK-3ß/caspase-1.

Doxorubicin (Dox) is a widely used clinical drug whose cardiotoxicity cannot be ignored. Pyroptosis (inflammatory cell death) has gradually gained attention in the context of Dox-induced cardiotoxicity. In addition to the inhibition of platelet activation by ticagrelor, little is known about its other pharmacological effects. Glycogen synthase kinase 3ß (GSK-3ß) has been shown to contribute to the pathological process of pyroptosis, but whether it is related to the potential role of ticagrelor is unclear. In this study, we investigated the effects of ticagrelor on Dox-induced pyroptosis in cardiomyocytes. Rats were treated with ticagrelor (7.5 mg/kg, i.g.) 1 h before intravenous injection of Dox (2.5 mg/kg), once every 3 days, six times in total. Hearts were collected for histochemical analysis and western blot detection 8 weeks after the last administration. Ticagrelor was shown to significantly improve cardiac function by inhibiting GSK-3ß/caspase-1/GSDMD activation. In vitro experiments were conducted using rat cardiac myocytes (RCMs) and rat embryonic cardiac-derived H9c2 cells. Pretreatment with ticagrelor (10 µm) significantly inhibited Dox (1 µm)-induced hypertrophy and reversed the upregulation of GSDMD-NT expression. We showed that ticagrelor suppressed the activation of Akt caused by Dox in the heart tissue as well as in RCMs/H9c2 cells caused by Dox. When GSK-3ß expression was absent in H9c2 cells, the inhibitory effect of ticagrelor on Dox-induced caspase-1/GSDMD activation was weakened. These data showed that ticagrelor reduced Dox-induced pyroptosis in rat cardiomyocytes by targeting GSK-3ß/caspase-1.

Metabolic engineering strategies for sesquiterpene production in microorganism.

Sesquiterpenes are a large variety of terpene natural products, widely existing in plants, fungi, marine organisms, insects, and microbes. Value-added sesquiterpenes are extensively used in industries such as: food, drugs, fragrances, and fuels. With an increase in market demands and the price of sesquiterpenes, the biosynthesis of sesquiterpenes by microbial fermentation methods from renewable feedstocks is acquiring increasing attention. Synthetic biology provides robust tools of sesquiterpene production in microorganisms. This review presents a summary of metabolic engineering strategies on the hosts and pathway engineering for sesquiterpene production. Advances in synthetic biology provide new strategies on the creation of desired hosts for sesquiterpene production. Especially, metabolic engineering strategies for the production of sesquiterpenes such as: amorphadiene, farnesene, bisabolene, and caryophyllene are emphasized in: Escherichia coli, Saccharomyces cerevisiae, and other microorganisms. Challenges and future perspectives of the bioprocess for translating sesquiterpene production into practical industrial work are also discussed.

Toward improved terpenoids biosynthesis: strategies to enhance the capabilities of cell factories.

Terpenoids form the most diversified class of natural products, which have gained application in the pharmaceutical, food, transportation, and fine and bulk chemical industries. Extraction from naturally occurring sources does not meet industrial demands, whereas chemical synthesis is often associated with poor enantio-selectivity, harsh working conditions, and environmental pollutions. Microbial cell factories come as a suitable replacement. However, designing efficient microbial platforms for isoprenoid synthesis is often a challenging task. This has to do with the cytotoxic effects of pathway intermediates and some end products, instability of expressed pathways, as well as high enzyme promiscuity. Also, the low enzymatic activity of some terpene synthases and prenyltransferases, and the lack of an efficient throughput system to screen improved high-performing strains are bottlenecks in strain development. Metabolic engineering and synthetic biology seek to overcome these issues through the provision of effective synthetic tools. This review sought to provide an in-depth description of novel strategies for improving cell factory performance. We focused on improving transcriptional and translational efficiencies through static and dynamic regulatory elements, enzyme engineering and high-throughput screening strategies, cellular function enhancement through chromosomal integration, metabolite tolerance, and modularization of pathways.

Natural ingredients from Chinese materia medica for pulmonary hypertension.

Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure, which may eventually develop to right heart failure and death. Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, limited types of effective and economical drugs for PH still makes it as a life-threatening disease. Some drugs from Chinese materia medica (CMM) have been traditionally applied in the treatment of lung diseases. Accumulating evidence suggests active pharmaceutical ingredients (APIs) derived from those medicines brings promising future for the prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH, so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.

Synergistic antibacterial polyacrylonitrile/gelatin nanofibers coated with metal-organic frameworks for accelerating wound repair.

Bacterial infections prolong the wound healing time and increase the suffering of patients, thus it is important to develop wound dressing that can inhibit bacterial infection. Herein, we use two methods including "doping method" and "secondary growth method" to prepare ZIF-8@gentamicin embedded in and coated on polyacrylonitrile/gelatin (PG) nanofibers, separately. Composite nanofibers prepared by the secondary growth method achieve higher drug loading than that of the doping method, and the release rate can be adjusted by pH. Simultaneously increasing drug loading and regulating its release rate are achieved in the secondary growth method, which cannot be achieved by the doping method. Furthermore, synergistic antibacterial property occurs in the composite nanofibers prepared by the secondary growth method, and gentamicin loaded on ZIF-8 promotes the antibacterial effect, which shows better antibacterial effect than the doping method. As a result, during the wound infection of mouse, composite nanofibers prepared by the secondary growth method exhibit a faster recovery effect than the doping method, which effectively shortened the wound healing time from 21 days to 16 days.

Dual Antibacterial Effect of In Situ Electrospun Curcumin Composite Nanofibers to Sterilize Drug-Resistant Bacteria.

Bacterial infection especially caused by multidrug-resistant bacteria still endangers human life. Photodynamic therapy (PDT) can effectively kill bacteria, and nanofiber-based PDT can effectively reduce damage to normal tissues. However, current photosensitizers coated on the surfaces of fibers would release to the wound, causing some side effects. And nanofibers prepared by traditional method exhibit poor adhesion on the wound, which severely reduces the PDT effect due to its short-range effect. Herein, core-shell curcumin composite nanofibers are prepared by in situ electrospinning method via a self-made portable electrospinning device. The obtained composite nanofibers show superior adhesiveness on different biological surface than that of traditional preparation method. Upon 808-nm irradiation, these composite nanofibers effectively produced singlet oxygen (1O2) without curcumin falling off. After these composite nanofibers' exposure to drug-resistant bacteria, they exhibit dual antibacterial behaviors and efficiently kill the drug-resistant bacteria. These dual antibacterial nanofiber membranes with excellent adhesiveness may benefit the application of wound infection as antibacterial dressing.

Association Between Anxiety Symptoms and Problematic Smartphone Use Among Chinese University Students: The Mediating/Moderating Role of Self-Efficacy.

Problematic smartphone use (PSU) is a novel manifestation of addictive behaviors. It is frequently reported to be correlated with anxiety symptoms among University students. However, the underlying mechanism has not yet been thoroughly studied. Whether the association between anxiety symptoms and PSU is mediated or moderated by self-efficacy remains unclarified. A cluster sampling cross-sectional study was thus conducted to explore the potential mediating or moderating effect of self-efficacy in Chinese University students. Participants (N = 1,113) were recruited from eight Universities in Shenyang, China. Of them, 146 did not effectively respond to the questionnaires. Thus, 967 participants were eligible for the final analysis. The mediating or moderating role of self-efficacy in the anxiety-PSU relationship was explored using hierarchical multiple regression. Then the mediation model was further verified using the SPSS macros program (PROCESS v3.0). Our results showed that anxiety symptoms was positively correlated with PSU (r = 0.302, P < 0.01), while self-efficacy was negatively correlated with anxiety symptoms and PSU (r = -0.271 and -0.181, P < 0.01). Self-efficacy partly mediated the relationship between anxiety symptoms and PSU, which accounted for ~17.5% of the total effect that anxiety symptoms have on PSU. However, the moderating effect of self-efficacy on the anxiety-PSU relationship was insignificant. In summary, our findings suggested that self-efficacy partly mediates but not moderates the link between anxiety symptoms and PSU among Chinese University students. Therefore, multicomponent interventions should be made to restrict the frequency of smartphone usage, enhance the level of self-efficacy, and thus promote the mental health status of University students.

Eluting mode of photodynamic nanofibers without photosensitizer leakage for one-stop treatment of outdoor hemostasis and sterilizing superbacteria.

Bleeding in outdoor environments is often accompanied by bacterial infection. Due to poor outdoor conditions, it is essential to use the same materials to achieve one-stop treatment of fast hemostasis and simultaneously sterilizing bacteria, especially multidrug-resistant bacteria. Photodynamic therapy (PDT) can kill superbacteria, and local PDT through a nanofiber platform can effectively reduce damage to normal tissue. However, current photosensitizers whether in the interior or on the surface of fibers would leak into the wound and inhibit collagen regeneration. Herein, we use a battery-powered handheld electrospinning device that can work outdoors. It directly spins fibers onto the wound, which facilitates fast hemostasis due to its excellent adhesion to the wound. Eluting holes in the hydrophobic fibers by wound tissue fluid are also proposed to accelerate the escape of reactive oxygen species (ROS) from the interior of the fibers to the wound. After photosensitizers were coated on upconverting nanoparticles (UCNPs), they formed clusters whose size (∼55 nm) was much larger than the uniform elution hole (∼4 nm), which prevented photosensitizers from leaking out into the wound tissue. This cluster structure can also tailor the photosensitizers to be triggered by near infrared (NIR) light, whose deeper penetration depth in tissue can facilitate treating deep infections. Because of the combination of the in situ fiber deposition method with the designed elution mode, ROS is effectively poured out onto the fiber surface and is quickly delivered to the wound. Thus, after rapid hemostasis (<7 s), this one-stop treatment followed by photodynamic sterilizing of superbacteria can promote collagen regeneration and reduce wound healing time from 24 to 16 days.

The Differing Roles of Cognitive Empathy and Affective Empathy in the Relationship Between Trait Anger and Aggressive Behavior: A Chinese College Students Survey.

Empathy is essential for effective social interaction. People often express the belief that empathy is closely related to aggressive behavior, but empirical data has challenged this assumption. However, there is a lack of research that focuses on the role of empathy in the relationship between trait anger and aggressive behavior. The current research focuses on the roles that different components of empathy have performed in the combinations of trait anger-hostile cognition-aggressive behavior link and attempt to identify, with reference to Integrated Model of Emotion Processes and Cognition in Social Information Processing, at which step this may occur. Participants included 663 undergraduate students who completed self-report measures of Trait Anger Scale, Aggressive Behavior Questionnaire, the Interpersonal Reactivity Index, and the Reactive-Proactive Aggression Questionnaire. Results from correlation analysis show that there is no significant correlation between cognitive empathy and aggressive behavior (r = -.06) but do however suggest a significant correlation between affective empathy and aggressive behavior (r = -.19). Results from structural equation modeling reveal that different components of empathy perform different roles in relation to aggressive behavior. The moderated mediating model analysis results show that cognitive empathy played a moderating role in both the direct effect and the first stage of the mediating model of trait anger-hostile cognition-aggression behavior. The results of multiple mediation model analysis demonstrate that affective empathy only played a partial mediating role between hostile cognition and aggressive behavior. This study contributes to understanding of Social Information Processing Models (SIPMs) and provides insight into the relationship between empathy and aggressive behavior.

Hymenobacter sediminis sp. nov., isolated from lake sediment.

A Gram-stain-negative, facultatively aerobic, rod-shaped, motile by gliding and pink-pigmented bacterial strain, designated ELS1360T, was isolated from a lake sediment sample collected in Inner Mongolia, PR China. Strain ELS1360T grew optimally at 33 °C, at pH 6.5-7.0 and without NaCl. Strain ELS1360T exhibited 97.3, 97.1 and 96.9 % 16S rRNA gene sequence similarities to Hymenobacter aquatilis HMF3095T, Hymenobacter luteus JCM 30328T and Hymenobacter latericoloratus JCM 30327T, respectively, and 90.4-96.9 % to other members of the genus Hymenobacter. Results of phylogenetic analysis based on 16S rRNA gene sequences showed that strain ELS1360T belonged to the genus Hymenobacter and clustered with H. luteus JCM 30328T and H. latericoloratus JCM 30327T. The predominant cellular fatty acids were iso-C15:0, summed feature 3 and C16:1ω5c. Strain ELS1360T contained MK-7 as the sole menaquinone. The major polar lipids contained phosphatidylethanolamine and two unidentified lipids. The genomic DNA G+C content of strain ELS1360T was 57.1 mol%. Based on the results of our phylogenetic, phenotypic, genotypic and chemotaxonomic analyses, it is concluded that strain ELS1360T represents a novel species within the genus Hymenobacter, for which the name Hymenobacter sediminis sp. nov. is proposed. The type strain is ELS1360T (=KCTC 62449T=MCCC 1H00319T).

A scale-down model of 4000-L cell culture process for inactivated foot-and-mouth disease vaccine production.

The anticipated increasing demand for inactivated foot-and-mouth (FMD) disease vaccine calls for its larger production capacity, while development of a large-scale process typically requires high running cost and has very limited experimental throughput at manufacturing scale. Thus, an economic scale-down model of representing a large-scale process becomes necessary and essential. In this study, we used a systematic approach to establish a scale-down model representing a 4000-L culture process for FMD vaccine production by suspension BHK-21 cells. In detail, we firstly compared hydrodynamic properties of three bioreactors (14-L, 800-L and 4000-L) under three different conditions (equivalent mixing time, equivalent shear stress and equivalent volumetric power). We figured out equivalent volumetric power (P/V) potentially as an appropriate scale-down strategy, since it resulted in comparable calculated hydrodynamic parameters among three bioreactors. Next, we used computational fluid dynamics (CFD) simulation to provide more details about hydrodynamic environments inside the bioreactors, which supports the reliability of this scale-down strategy. Finally, we compared cell growth, metabolites, vaccine productivity and product quality attributes during FMD vaccine production by BHK-21 cells and observed very close performances among three bioreactors, which once again demonstrates the robustness of this scale-down model. This scale-down strategy can be applied to study variations and critical quality attributes (CQAs) in the resultant production process based on quality by design (QbD) principles, aiming at further more efficient optimization of vaccine production.

Paracnuella aquatica gen. nov., sp. nov., a member of the family Chitinophagaceae isolated from a hot spring.

A Gram-stain-negative, rod-shaped bacterium (designated strain N24T) with gliding motility was isolated from thermal spring water sampled at Xi'an, PR China. Cells were 0.4-0.8 µm wide and 1.8-7.8 µm long. Optimal growth occurred at 33 °C and pH 7.0 on Reasoner's 2A (R2A) agar. Strain N24T could produce exopolysaccharide on R2A agar at 33 °C. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain N24T formed a distinct phyletic lineage within the family Chitinophagaceae and was most closely related to members of the genera Flavisolibacter, Cnuella, Niveitalea, Flavitalea, Flaviaesturariibacter and Niastella with 91.7-93.9 % 16S rRNA gene sequence similarities. The major fatty acids of strain N24T were iso-C15 : 0 (31.8 %), iso-C17 : 0 3-OH (16.1 %) and iso-C15 : 1 G (12.9 %). The polar lipid profile consisted of phosphatidylethanolamine, two aminolipids and six unknown lipids; the quinone system consisted of menaquinone-7 (MK-7). The genomic G+C content was 49.3 mol%. On the basis of the evidence presented in this study, strain N24T represents a novel species of a new genus in the family Chitinophagaceae, for which the name Paracnuella aquatica gen. nov., sp. nov. is proposed. The type species is N24T (=KCTC 62083T=MCCC 1H00301T).

Efficacy of ivabradine for heart failure: A protocol for a systematic review of randomized controlled trial.

BACKGROUND: Previous clinical trials have reported that ivabradine can effectively treat heart failure (HF). However, no systematic review has explored its efficacy and safety for HF. This systematic review will aim to evaluate the efficacy and safety of ivabradine for the treatment of patients with HF. METHODS: We will search the literature from the following electronic databases from inception to the January 31, 2019: Cochrane Central Register of Controlled Trials, EMBASE, MEDILINE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data. All randomized controlled trials (RCTs) of ivabradine for HF will be fully considered for inclusion without any restrictions. Additionally, grey literature including clinical trial registries, dissertations, and reference lists of included studies, conference abstracts will also be searched. Two researchers will review these literatures, extract data, and assess risk of bias of included RCTs separately. Data will be pooled by either fixed-effects model or random-effects model, and meta-analysis will be conducted if it is appropriate. RESULTS: The primary outcome is all-cause mortality. The secondary outcomes comprise of change in body weight, urine output, change in serum sodium, and all adverse events. CONCLUSIONS: The results of this study will summary provide up-to-dated evidence for assessing the efficacy and safety of ivabradine for HF. ETHICS AND DISSEMINATION: It is not necessary to acquire ethical approval for this systematic review, because no individual patient data will be used in this study. The results of this systematic review will be published through peer-reviewed journals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019120814.

Engineering and manipulation of a mevalonate pathway in Escherichia coli for isoprene production.

Isoprene is a useful phytochemical with high commercial values in many industrial applications including synthetic rubber, elastomers, isoprenoid medicines, and fossil fuel. Currently, isoprene is on large scale produced from petrochemical sources. An efficient biological process for isoprene production utilizing renewable feedstocks would be an important direction of research due to the fossil raw material depletion and air pollution. In this study, we introduced the mevalonate (MVA) pathway genes/acetoacetyl-coenzyme A thiolase (mvaE) and MVA synthase (mvaS) from Enterococcus faecalis (E. faecalis); MVA kinase (mvk) derived from Methanosarcina mazei (M. mazei); and phosphomevalonate kinase (pmk), diphosphomevalonate decarboxylase (mvaD), and isopentenyl diphosphate isomerase (idi) from Streptococcus pneumoniae (S. pneumoniae) to accelerate dimethylallyl diphosphate (DMAPP) accumulation in Escherichia coli (E. coli). Together with a codon-optimized isoprene synthase (ispS) from Populus alba (P. alba), E. coli strain succeeded in formation of isoprene. We then manipulated the heterologous MVA pathway for high-level production of isoprene, by controlling the gene expression levels of the MVA pathway genes. We engineered four E. coli strains which showed different gene expression levels and different isoprene productivities, and we also characterized them with quantitative real-time PCR and metabolite analysis. To further improve the isoprene titers and release the toxicity to cells, we developed the extraction fermentation by adding dodecane in cultures. Finally, strain BL2T7P1TrcP harboring balanced gene expression system produced 587 ± 47 mg/L isoprene, with a 5.2-fold titer improvement in comparison with strain BL7CT7P. This work indicated that a balanced metabolic flux played a significant role to improve the isoprene production via MVA pathway.