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1.
J Cardiothorac Surg ; 15(1): 75, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381035

RESUMO

OBJECTIVES: This study aimed to identify Chinese parents' knowledge and attitudes toward transthoracic device closure of ventricular septal defect (VSD). METHODS: This cross-sectional study collected data on a total of 203 Chinese parents of patients with VSD were included, and an author-designed three-page questionnaire was used. RESULTS: A total of 73.9% of the parents had heard of transthoracic device closure of VSD; however, they lacked detailed knowledge. 88.2% parents expressed their willingness to undergo this procedure. Although there was no significant correlation between knowledge about the occluder material and acceptance of the method, knowledge of other information was significantly related to willingness to undergo the procedure. Some parents expressed some concerns and high expectations, but the postoperative risk reduced their desire for accepting the procedure. This study also found that most parents did not have a detailed understanding of such procedure. CONCLUSION: Parents of patients with VSD in China need continued education regarding transthoracic device closure of VSD, especially in terms of its benefits and limited postoperative complications. In addition, it is essential to reduce the cost of this procedure to promote its development and application.

2.
J Cardiothorac Surg ; 15(1): 81, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393300

RESUMO

OBJECTIVE: The purpose of this study was to explore the effects of music therapy on pain, anxiety and depression in patients after coronary artery bypass grafting. METHODS: A retrospective study of 99 patients after coronary artery bypass from January 2017 to January 2019 was conducted in a cardiac center in China. According to the different interventions, all the participants were divided into 3 groups: group A: music therapy; group B: rest without music therapy; and group C: conventional treatment. The Numerical Rating Scale (NRS), Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were used to measure the patient's pain, anxiety and depression before and after 30 min of the intervention. RESULTS: There were no significant differences in the NRS, SDS and SAS scores between the three groups of patients before the intervention. After 30 min of music therapy, the NRS, SDS and SAS scores of patients in group A were significantly lower than those before music therapy, and the differences were statistically significant. However, before and after the intervention in groups B and C, the NRS, SDS and SAS scores were not statistically significant. By comparison among the three groups after 30 min of intervention, the NRS, SDS and SAS scores in patients in group A were significantly lower than those in groups B and C, and the differences were statistically significant. The scores were not significantly different between groups B and C. CONCLUSION: Music therapy can effectively alleviate the pain, anxiety and depression of patients after coronary artery bypass grafting.

3.
J Cardiothorac Surg ; 15(1): 88, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398010

RESUMO

OBJECTIVE: This article aimed to study the quality of life and anxiety of sexagenarian patients who underwent aortic biological vs mechanical valve replacement in a single center in China. METHODS: The clinical data of 78 patients aged 60 to 70 years who underwent aortic prosthetic valve replacement were retrospectively analyzed in our hospital from June 2017 to February 2018. Patients were divided into two groups depending on the type of prosthetic valve they received (biological valve group vs mechanical valve group). The SF-36 was completed by all patients at discharge and at one-year follow-up, and the cardiac anxiety questionnaire (CAQ) was also completed at one-year follow-up. RESULTS: There was no statistically significant difference between the two groups in general clinical data or SF-36 score at discharge. However, at one-year follow-up, the SF-36 scores were significantly higher in the biological valve group than in the mechanical valve group, and the CAQ scores in fear and anxiety, avoidance and attention in the mechanical valve group were significantly higher than those in the biological valve group. CONCLUSIONS: Based on the postoperative quality of life and anxiety scores of sexagenarian patients who underwent biological vs mechanical valve replacement in this study, a biological valve has more value than a mechanical valve for sexagenarians undergoing aortic valve replacement.

4.
Nanoscale ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32400835

RESUMO

Engineering coordination compounds, e.g., prussian blue (PB) and its analogues (PBAs), with designable complex nanostructures via chemical etching holds great opportunities for improving energy storage performances by adjusting topological geometry, selectively exposing active sites, tuning electronic properties and enhancing accessible surface area. Unfortunately, it remains ambiguous particularly on site-selective and anisotropic etching behaviors. Herein, for the first time, we propose that two distinct regions are formed inside NiCo PBA (NCP) cubes due to the competition between classical ion-by-ion crystallization and non-classical crystallization based on aggregation. Such a unique structure ultimately determines not only the etching position but also the anisotropic pathway by selectively exposing unprotected Ni sites. According to this principle, complex PBA architectures, including nanocages, open nanocubes (constructed by six cones sharing the same apex), nanocones, and chamfer nanocubes can be intentionally obtained. After thermal annealing, NCP nanocones are converted to morning glory-like porous architectures composed of NiO/NiCo2O4 heterostructures with a mean particle size of 5 nm, which show improved rate performance and cycling stability.

5.
J Cardiothorac Surg ; 15(1): 72, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375843

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the effect of continuous nursing interventions on valve noise-related anxiety in patients undergoing mechanical mitral valve replacement (MVR) and to analyze its impact on patient quality of life. METHODS: Ninety patients who underwent mechanical MVR were divided into two groups. All patients in group A received routine nursing care. In addition to this intervention, an assigned nurse periodically provided patients in group B with continuous nursing interventions and ongoing health consultations during a 1-year follow-up. A hospital anxiety and depression (HAD) scale, a customized questionnaire and a Short Form Health Status 36 (SF-36) score questionnaire were used as the research tools. RESULTS: The postoperative HAD scores were better in group B than in group A, but the differences in most of the data were not statistically significant between the groups, except for HA sections 0-7 and 11-21. Based on the customized questionnaire, the subjective disturbance level was significantly lower in group B than in group A (the results of Q1 and Q4 were statistically significant). With regard to the SF-36 scores, group B was superior to group A in general health, emotional function and mental health, while the other dimensions had no significant difference. CONCLUSIONS: Compared with routine care, patients who received continuous care intervention after mechanical MVR had fewer anxiety symptoms and better quality of life.

6.
Drug Des Devel Ther ; 14: 1717-1727, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32440097

RESUMO

Purpose: Oral squamous cell carcinoma (OSCC) is a common malignancy of the oral cavity. As the survival rate of OSCC patients is low, it is crucial to explore new markers and therapeutic targets for early diagnosis of the disease. A high level of actinin alpha 1 (ACTN1) in patients could serve as an independent prognostic factor of acute myeloid leukemia. However, the role of ACTN1 in OSCC remains unclear. In the present study, we aimed to investigate the role of ACTN1 in OSCC. Methods: ACTN1 protein levels in tissues were determined by immunohistochemical (IHC) staining. The correlation of ACTN1 expression with clinicopathological features and prognosis was analyzed. Univariate and multivariate analyses were performed. The effect of ACTN1 knockdown on cell proliferation, migration, invasion, apoptosis, epithelial-mesenchymal transition (EMT), and the cell cycle was evaluated using Western blotting, Cell Counting Kit­8 (CCK8) assays, flow cytometry analysis, transwell assays, wound-healing assays, and nude mouse models of subcutaneous xenograft and pulmonary metastasis. Results: Based on the total score of ACTN1 IHC staining analysis, ACTN1 expression was found to be low in 10 normal mucosal tissues, 48 normal mucosal tissues adjacent to OSCC, and 19 OSCC tissues, but high in 29 OSCC tissues. ACTN1 protein levels were significantly associated with the clinical stage and node metastasis, and a high ACTN1 protein level indicated poor prognosis. Moreover, ACTN1 expression was an independent predictor of poor prognosis of OSCC. Using in vitro assays, we found that ACTN1 knockdown could induce cell cycle arrest, promote apoptosis, and inhibit EMT and cell proliferation, migration, and invasion in the OSCC cell lines, SCC-15 and HSC-3. Moreover, ACTN1 knockdown inhibited subcutaneous tumor growth and pulmonary metastasis in vivo. Conclusion: ACTN1 levels were significantly associated with the clinical stage and node metastasis, and a high ACTN1 protein level indicated poor prognosis. Moreover, ACTN1 knockdown could suppress cell proliferation and metastasis of OSCC. Our results suggested that ACTN1 may serve as a diagnostic and prognostic marker of OSCC.

7.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(5): 419-424, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32434634

RESUMO

OBJECTIVE: To study the clinical features of coronavirus disease 2019 (COVID-19) in children aged <18 years. METHODS: A retrospective analysis was performed from the medical data of 23 children, aged from 3 months to 17 years and 8 months, who were diagnosed with COVID-19 in Jiangxi, China from January 21 to February 29, 2020. RESULTS: Of the 23 children with COVID-19, 17 had family aggregation. Three children (13%) had asymptomatic infection, 6 (26%) had mild type, and 14 (61%) had common type. Among these 23 children, 16 (70%) had fever, 11 (48%) had cough, 8 (35%) had fever and cough, and 8 (35%) had wet rales in the lungs. The period from disease onset or the first nucleic acid-positive detection of SARS-CoV-2 to the virus nucleic acid negative conversion was 6-24 days (median 12 days). Of the 23 children, 3 had a reduction in total leukocyte count, 2 had a reduction in lymphocytes, 2 had an increase in C-reactive protein, and 2 had an increase in D-dimer. Abnormal pulmonary CT findings were observed in 12 children, among whom 9 had patchy ground-glass opacities in both lungs. All 23 children received antiviral therapy and were recovered. CONCLUSIONS: COVID-19 in children aged <18 years often occurs with family aggregation, with no specific clinical manifestation and laboratory examination results. Most of these children have mild symptoms and a good prognosis. Epidemiological history is of particular importance in the diagnosis of COVID-19 in children aged <18 years.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32365023

RESUMO

We present an image projection network (IPN), which is a novel end-to-end architecture and can achieve 3D-to-2D image segmentation in optical coherence tomography angiography (OCTA) images. Our key insight is to build a projection learning module (PLM) which uses a unidirectional pooling layer to conduct effective features selection and dimension reduction concurrently. By combining multiple PLMs, the proposed network can input 3D OCTA data, and output 2D segmentation results such as retinal vessel segmentation. It provides a new idea for the quantification of retinal indicators: without retinal layer segmentation and without projection maps. We tested the performance of our network for two crucial retinal image segmentation issues: retinal vessel (RV) segmentation and foveal avascular zone (FAZ) segmentation. The experimental results on 316 OCTA volumes demonstrate that the IPN is an effective implementation of 3D-to-2D segmentation networks, and the uses of multi-modality information and volumetric information make IPN perform better than the baseline methods.

9.
Aquat Toxicol ; 224: 105497, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32388340

RESUMO

Previous research has identified microplastics as new environmental pollutants that are widely distributed in a variety of environments, including aquaculture environments. However, the potential hazard of microplastics to aquaculture animals, especially toward lipid metabolism involved with the survival and growth of aquatic animal, has not yet been investigated. In the present study, redclaw crayfish (Cherax quadricarinatus) were exposed to different concentrations of 200 nm-sized polystyrene microspheres (0, 0.5, and 5 mg/L) for 21 days, to investigate the effects of microplastics on lipid metabolism. After ingestion, the microplastics were distributed in the intestines and hepatopancreas, and appeared to inhibit the growth of Cherax quadricarinatus. Subsequently, the lipid levels in the hepatopancreas and hemolymph was detected, and found that after 21 days of exposure, the lipid content and free fatty acids in the hepatopancreas and hemolymph decreased significantly, and total cholesterol and triglycerides levels increased significantly in the hemolymph. This might have been caused by insufficient intake of exogenous fat. A significant decrease in lipase activity also supported this view. The activity of lipoprotein lipase related to lipolysis in the hepatopancreas increased significantly, while the activity of fatty acid synthase related to fat synthesis increased, and the activity of acetyl-CoA carboxylase decreased. These results indicated disturbed lipid metabolism in the hepatopancreas. The significant increase of lipid transport-related low-density lipoprotein indicated that the lipolytic capacity was higher than the lipid synthesis capacity. The expression levels of fatty acid metabolism-related genes FAD6 and FABP decreased significantly, indicating that the fatty acid utilization ability of hepatopancreas cells was inhibited, which was consistent with the results of enzyme activities. Thus, microplastics represent a potential hazard to redclaw crayfish, at least on lipid metabolism. This study provided basic data on the ecotoxicological effects of microplastics on crustaceans.

10.
Small ; : e2000653, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32432831

RESUMO

Fiber-based supercapacitors (FSCs) possess great potential as an ideal type of power source for future weaveable/wearable electronics and electronic-textiles. The performance of FSCs is, without doubt, primarily determined by the properties of fibrous electrodes. Carbonaceous fibers, e.g., commercial carbon fibers, newly developed graphene fibers, and carbon nanotube fibers, are deemed as promising materials for weaveable/wearable supercapacitors owing to their exotic properties including high tensile strength and robustness, excellent electrical conductivity, good flexibility, and environmental stability. Nevertheless, bare carbonaceous fiber normally exhibits low capacitance originating from electric double-layer capacitance, which remains unsatisfactory for efficiently powering wearable and portable devices. Numerous efforts have been devoted to tailoring fiber properties by hybridizing pseudocapacitive materials, and impressive progress has been achieved thus far. Herein, the microstructures of pristine carbonaceous fibers are introduced in detail, and the recent advances in rational nano/microstructure design of their hybrids, which provides the feasibility to achieve the synergistic interaction between conductive agents and pseudocapacitive nanomaterials but are normally overlooked, are comprehensively reviewed. Besides, the challenges in developing high-performance fibrous electrodes are also elaborately discussed.

11.
J Comp Physiol B ; 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32274534

RESUMO

The Xizang plateau frog, Nanorana parkeri, has the highest altitudinal distribution of all frogs in the world and survives the cold of winter without feeding by entering into a hibernating state. However, little attention has been paid to its physiological and biochemical characteristics that support overwintering underwater in small ponds. Here, we measured metabolic rate and heart rate, and collected liver and muscle samples from N. parkeri in summer and winter for analysis of mitochondrial respiration rate, and activities and relative mRNA transcript expression of metabolic enzymes. Compared with summer-collected frogs, both resting metabolic rate and heart rate were significantly reduced in winter-collected frogs. Both state 3 and state 4 respiration of liver mitochondria were also significantly reduced in winter but muscle mitochondria showed a decline only in state 3 respiration in winter. The activities and corresponding mRNA expression of cytochrome c oxidase showed a marked decline in winter, whereas the activities and corresponding mRNA expression of lactate dehydrogenase increased in winter-collected frogs, compared to summer. The thermal sensitivity (Q10 values) for state 3 respiration rate by liver mitochondria, and activities of lactate dehydrogenase, and cytochrome c oxidase all increased in winter-collected frogs, compared with summer frogs, suggesting that overwintering frogs were more sensitive to changes in external temperature. Enzyme changes mainly result from lower overall quantities of these enzymes as well as post-translational modifications. We conclude that overwintering N. parkeri exhibit a seasonal, temperature-independent suppression of metabolism that is mediated at multiple levels: physiological, mitochondrial, gene expression and enzyme activity levels.

12.
Comput Human Behav ; : 106380, 2020 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-32292239

RESUMO

During times of public crises, governments must act swiftly to communicate crisis information effectively and efficiently to members of the public; failure to do so will inevitably lead citizens to become fearful, uncertain and anxious in the prevailing conditions. This pioneering study systematically investigates how Chinese central government agencies used social media to promote citizen engagement during the COVID-19 crisis. Using data scraped from 'Healthy China', an official Sina Weibo account of the National Health Commission of China, we examine how citizen engagement relates to a series of theoretically relevant factors, including media richness, dialogic loop, content type and emotional valence. Results show that media richness negatively predicts citizen engagement through government social media, but dialogic loop facilitates engagement. Information relating to the latest news about the crisis and the government's handling of the event positively affects citizen engagement through government social media. Importantly, all relationships were contingent upon the emotional valence of each Weibo post.

13.
J Med Virol ; 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32275072

RESUMO

The outbreak of the infection of 2019 novel coronavirus disease (COVID--19) has become a challenging public health threat worldwide. Limited data are available for pregnant women with COVID-19 pneumonia. We report a case of a convalescing pregnant woman diagnosed with COVID-19 infection 37 days before delivery in the third trimester. A live birth without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was performed successfully via the vagina. The findings from our case indicate that there is no intrauterine transmission in this woman who developed COVID-19 pneumonia in late pregnancy.

14.
Chem Commun (Camb) ; 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32296798

RESUMO

The selective adsorption/separation of C2 hydrocarbons has been realized in a "flexible-robust" MOF, Zn2(Atz)2Ox. Owing to the distinctive guest-dependent multistep adsorption behaviors and suitable guest-framework interactions, this MOF shows outstanding separation performance for C2H2/C2H4 mixtures in a wide range of temperature confirmed by a column breakthrough experiment.

15.
Inorg Chem ; 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32309935

RESUMO

The metal-metal bond in metal-rich chalcogenide is known to exhibit various structures and interesting physical properties. Ta2Se can be obtained by both arc-melting and solid-state pellet methods. Ta2Se crystallizes a layered tetragonal structure with space group P4/nmm (No. 129; Pearson symbol tP6). Each unit cell consists of four layers of body-centered close-packing Ta atoms sandwiched between two square nets of Se atoms, forming the Se-Ta-Ta-Ta-Ta-Se networks. Herein, we present magnetic susceptibility, resistivity, and heat capacity measurements on Ta2Se, which together indicate bulk superconductivity with Tc = 3.8(1) K. According to first-principles calculations, the d orbitals in Ta atoms dominate the Fermi level in Ta2Se. The flat bands at the Γ point in the Brillouin zone yield the van Hove singularities in the density of states around the Fermi level, which is intensified by introducing a spin-orbit coupling effect, and thus could be critical for the superconductivity in Ta2Se. The physical properties, especially superconductivity, are completely different from those of Ta-rich alloys or transition-metal dichalcogenide TaSe2.

16.
Sci Total Environ ; 724: 138309, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32272413

RESUMO

Transition metals in airborne particulate matter, especially those with aerodynamic diameters no more than 2.5 µm (PM2.5), have attracted considerable attention due to their potential environmental and human health risks. However, determination of these potential risks requires comprehensive knowledge of their dissolution behavior and residual size in aqueous media. Herein, we describe an analytical method for on-line determination of the soluble fraction of Zn as a model transition metal and the size of residual PM2.5 using hollow fiber flow field-flow fractionation (HF5) coupled with UV-vis absorption spectroscopy and inductively coupled plasma optical emission spectroscopy. HF5 was directly applied on the incubated samples in pure water (PW), simulated natural water (SNW), and simulated lung fluid (SLF) due to its efficient in-line filtration and excellent fractionation resolution. Firstly, the potential of the proposed method (under optimized conditions) for size characterization was assessed against commercial silica microparticles, and results in good agreement with manufacturer and scanning electron microscopy values were obtained. The accuracy of quantification of soluble Zn in various media was then validated using a standard reference material in terms of satisfactory recoveries compared with the reference values. For the real PM2.5 samples collected from different sites in Beijing, China, the soluble Zn percentages in PW, SNW, and SLF were within 15.4-16.7%, 10.6-12.7%, and 43.1-46.9%, respectively, with the amount of particles smaller than ~10 nm released from PM2.5 increasing in the order of SNW < PW < SLF. The proposed HF5-based method provides a powerful and efficient tool for the quantification of soluble transition metal fractions and size characterization of residual particles with reduced analysis times, thus possessing great promise in real-time tracking of the transformation of PM2.5 in environmental and physiological media and in risk assessment.

17.
Int J Mol Sci ; 21(6)2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32244994

RESUMO

The development of monoclonal antibodies (mAbs) has provided vast opportunities to treat a wide range of diseases from cancer to viral infections. While plant-based production of mAbs has effectively lowered the upstream cost of mAb production compared to mammalian cell cultures, further optimization of downstream processing, especially in extending the longevity of Protein A resin by an effective bulk separation step, will further reduce the overall prohibitive cost of mAb production. In this study, we explored the feasibility of using aqueous two-phase separation (ATPS) in capturing and separating plant-made mAbs from host proteins. Our results demonstrated that an anti-West Nile virus mAb (E16) was efficiently separated from most plant host proteins by a single ATPS step, comprising the mixing of plant extracts containing Hydrophobin-Protein A fusion protein (HPA) and E16 and the subsequent incubation with an inexpensive detergent. This simple ATPS step yielded a highly enriched E16 mAb preparation with a recovery rate comparable to that of Protein A chromatography. The ATPS-enriched E16 retained its structural integrity and was fully functional in binding its target antigen. Notably, HPA-based ATPS was also effective in enriching E16 from plant host proteins when both HPA and E16 were produced in the same leaves, supporting the potential of further streamlining the downstream purification process. Thus, ATPS based on plant-produced HPA in unpurified extract is a cost-effective yet efficient initial capture step for purifying plant-made mAbs, which may significantly impact the approach of mAb purification.

18.
J Clin Invest ; 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32255767

RESUMO

Food allergies are a major clinical problem and are driven by IgE antibodies specific for food antigens. T follicular regulatory (TFR) cells are a specialized subset of Foxp3+ T cells that modulate antibody responses. Here we analyzed the role of TFR cells in regulating antigen-specific IgE using a peanut-based food allergy model in mice. Peanut-specific IgE titers and anaphylaxis responses were significantly blunted in TFR cell-deficient Foxp3-cre Bcl6-fl/fl mice. Loss of TFR cells led to greatly increased non-specific IgE levels, showing that TFR cells have both helper and suppressor functions on IgE production in the GC that work together to facilitate the production of antigen-specific IgE. Foxp3-cre Pten-fl/fl mice with augmented TFR cell responses had markedly higher levels of peanut-specific IgE, revealing an active helper function by TFR cells on antigen-specific IgE. The helper function of TFR cells for IgE production involves IL-10, and the loss of IL-10 signaling by B cells led to a severely curtailed peanut-specific IgE response, decreased GC B cell survival and loss of GC dark zone B cells after peanut sensitization. We thus reveal that TFR cells have an unexpected helper role in promoting food allergy and are a novel target for drug development.

19.
Cardiol Young ; 30(5): 599-606, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32308178

RESUMO

BACKGROUND: Outcome data of doubly committed subarterial ventricular septal defect closure in adults are limited. METHODS: A review was made of the inpatients >18 years of age who underwent doubly committed subarterial ventricular septal defect closure between June 2010 and June 2017. RESULTS: The patients were categorised into two groups: The valve intervention group consisted of 31 patients who underwent aortic valvuloplasty, aortic valve replacement, or repair of sinus Valsalva aneurysm in addition to doubly committed subarterial ventricular septal defect closure; non-valvular intervention group comprised 58 patients who underwent only doubly committed subarterial ventricular septal defect closure. The groups did not differ by sex and age. Patients in the valve intervention group, with a larger ventricular septal defect size, were shorter and tended to be lighter. The valve intervention group had more patients with pneumonia perioperatively. No infective endocarditis and reoperation were noted during the study period. At last follow-up, 91 and 96.6% of the studied patients were free from left ventricle dilation and pulmonary hypertension. In patients without pre-operative aortic regurgitation, 12 developed new mild aortic regurgitation during the follow-up. CONCLUSIONS: About 34.8% of adult patients with doubly committed subarterial ventricular septal defect required concurrent intervention on aortic valve or sinus Valsalva aneurysm. The midterm results of doubly committed subarterial ventricular septal defect closure in adult patients were favourable. However, the incidence of new mild aortic regurgitation after ventricular septal defect closure was high (27.3%). Long-term follow-up of aortic regurgitation progression is needed.

20.
ChemMedChem ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32233075

RESUMO

Gramicidin S (GS), one of the most widely investigated antimicrobial peptides (AMPs), is known for its robust antimicrobial activity. However, it is restricted to topical application due to undesired hemolytic activity. With the aim of obtaining nontoxic GS analogues, we describe herein a molecular approach in which the native GS ß-turn region is replaced by synthetic ß,γ-diamino acids (ß,γ-DiAAs). Four ß,γ-DiAA diastereomers were employed to mimic the ß-turn structure to afford GS analogues GS3-6, which exhibit diminished hemolytic activity. A comparative structural study demonstrates that the (ßR,γS)-DiAA is the most-stable ß-turn mimic. To further improve the therapeutic index (e. g., high antibacterial activity and low hemolytic activity) and to extend the molecular diversity, GS5 and GS6 were used as structural scaffolds to introduce additional hydrophobic or hydrophilic groups. We show that GS6K, GS6F and GS display comparable antibacterial activity, and GS6K and GS6F have significantly decreased toxicity. Moreover, antibacterial mechanism studies suggest that GS6K kills bacteria mainly through the disruption of the membrane.

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