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Biological degradation of PET plastic holds great potential for plastic recycling. However, the high costs associated with preparing free enzymes for degrading PET make it unfeasible for industrial applications. Hence, we developed various cell catalysts by surface-displaying PETase mutants and MHETase using autotransporters in E. coli and P. putida. The efficiency of surface display was enhanced through modifying the host, co-expressing molecular chaperones, and evoluting the autotransporter. In strain EC9F, PET degradation rate was boosted to 3.85 mM/d, 51-fold and 23-fold increase compared to free enzyme and initial strain ED1, respectively. The reusability of cell catalyst EC9F was demonstrated with over 38 % and 30 % of its initial activity retained after 22 cycles of BHET degradation and 3 cycles of PET degradation. The highest reported PET degradation rate of 4.95 mM/d was achieved by the dual-enzyme cascade catalytic system EC9F+EM2+R, a mixture of cell catalyst EC9F and EM2 with surfactant rhamnolipid.
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Escherichia coli , Mutação , Escherichia coli/genética , Pseudomonas putida/enzimologia , Pseudomonas putida/genética , Polietilenotereftalatos/química , Polietilenotereftalatos/metabolismo , Catálise , Biocatálise , Biodegradação AmbientalRESUMO
BACKGROUND: Macitentan, either as monotherapy or part of combination therapy, improved clinical outcomes in patients with pulmonary artery hypertension (PAH) in clinical trials. Evidence on the effectiveness and safety of macitentan administered in real-world clinical practice in China is limited. METHODS: This real-world, retrospective, multicenter chart review study was conducted at seven hospitals in China. Adult patients with a diagnosis of PAH who initiated macitentan and had medical assessments at 3-7 months after macitentan initiation were included. The primary outcomes were changes in the World Health Organization functional class (WHO-FC), 6-min walk distance (6MWD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP)/B-type natriuretic peptide from baseline to first follow-up visit (months 3-7). Serious adverse events (SAEs) and adverse drug reactions (ADRs) of macitentan were collected. RESULTS: From 30 August 2021 to 31 March 2022, 214 eligible patients were included in the safety analysis set and 105 patients were included in the analysis of effectiveness. At the first follow-up visit compared with baseline, significant changes in WHO-FC were observed (p = .04), 93.5% patients had their WHO-FC improved (25.8%) or maintained (67.7%). 6MWD changed by a mean (standard deviation [SD]) of 45.0 (81.4) meters (p < .001), with 94.7% having their 6MWD improved (34.7%) or maintained (60.0%). The mean (SD) of NT-proBNP decreased from 1667.4 (3233.0) ng/L to 1090.0 (2230.1) ng/L (p < .001). In the safety analysis set, 24 (11.2%) patients experienced at least one ADR and/or SAE. ADRs and SAEs were reported in 11 (5.1%) and 18 (8.4%), respectively. No deaths or unexpected safety events were observed. CONCLUSION: This study provided real-world evidence on the clinical benefits and good tolerance of macitentan in Chinese patients with PAH treated in routine clinical practice.
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Sesquiterpenes and tetraterpenes are classes of plant-derived natural products with antineoplastic effects. While plant extraction of the sesquiterpene, germacrene A, and the tetraterpene, lycopene suffers supply chain deficits and poor yields, chemical synthesis has difficulties in separating stereoisomers. This review highlights cutting-edge developments in producing germacrene A and lycopene from microbial cell factories. We then summarize the antineoplastic properties of ß-elemene (a thermal product from germacrene A), sesquiterpene lactones (metabolic products from germacrene A), and lycopene. We also elaborate on strategies to optimize microbial-based germacrene A and lycopene production.
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Antineoplásicos , Licopeno , Sesquiterpenos de Germacrano , Licopeno/metabolismo , Sesquiterpenos de Germacrano/metabolismo , Antineoplásicos/metabolismo , Humanos , Carotenoides/metabolismo , Carotenoides/química , Sesquiterpenos/metabolismo , Vias BiossintéticasRESUMO
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.
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Angioplastia com Balão , Hipertensão Pulmonar , Embolia Pulmonar , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/terapia , Estudos Retrospectivos , Estudos de Coortes , Doença Crônica , Pulmão/diagnóstico por imagem , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/métodos , Perfusão , Artéria Pulmonar/diagnóstico por imagemRESUMO
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.
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Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/genética , Licopeno , Transporte Biológico , Morte Celular , Membrana Celular , Lipoproteínas , Proteínas de Escherichia coli/genéticaRESUMO
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.
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Escherichia coli , Sesquiterpenos , Escherichia coli/genética , Escherichia coli/metabolismo , Engenharia Metabólica/métodos , Acetilcoenzima A/metabolismo , Sesquiterpenos/metabolismo , Carbono/metabolismoRESUMO
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 structuresâ0D RNA scaffolds and 2D RNA scaffoldsâusing 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.
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Aptâmeros de Nucleotídeos , Engenharia Metabólica , Engenharia Metabólica/métodos , Ácido Mevalônico/metabolismo , Escherichia coli/metabolismo , RNA/metabolismo , Aptâmeros de Nucleotídeos/metabolismo , Redes e Vias Metabólicas/genéticaRESUMO
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.
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Estruturas Metalorgânicas , Nanopartículas , Agrobacterium tumefaciens/metabolismo , Biocatálise , Cobalto , Estabilidade Enzimática , Enzimas Imobilizadas/metabolismo , Frutose , Concentração de Íons de Hidrogênio , Fenômenos Magnéticos , Racemases e EpimerasesRESUMO
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.
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Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Angiografia , Fluordesoxiglucose F18/metabolismo , Glicólise , Prognóstico , Artéria Pulmonar/diagnóstico por imagem , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Carga TumoralRESUMO
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.
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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.
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Engenharia Metabólica , Sesquiterpenos , Escherichia coli/genética , Saccharomyces cerevisiae/genética , TerpenosRESUMO
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.
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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.
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Medicamentos de Ervas Chinesas , Hipertensão Pulmonar , Materia Medica , China , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Medicina Tradicional ChinesaRESUMO
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.
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Resinas Acrílicas/farmacologia , Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Gelatina/farmacologia , Estruturas Metalorgânicas/farmacologia , Nanofibras/química , Cicatrização/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Concentração de Íons de Hidrogênio , Masculino , Testes de Sensibilidade Microbiana , Nanofibras/ultraestrutura , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
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.
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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.
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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 (â¼55 nm) was much larger than the uniform elution hole (â¼4 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.
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Nanofibras , Nanopartículas , Fotoquimioterapia , Hemostasia , Raios Infravermelhos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
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.
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Agressão , Empatia , Ira , China , Cognição , Humanos , Estudantes , Inquéritos e QuestionáriosRESUMO
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).
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Cytophagaceae/classificação , Sedimentos Geológicos/microbiologia , Lagos/microbiologia , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , Cytophagaceae/isolamento & purificação , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfatidiletanolaminas/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMO
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.