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1.
Nanotechnology ; 31(5): 055702, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31671071

RESUMO

Filtering of industrial PM2.5 is a major challenge for global environmental and animal protection. Filtering of materials with excellent thermal stability and other comprehensive performances is required for the removal of fine particles in high-temperature operating industries such as steel, cement, metallurgy, incineration, etc. In this study, a meta-aramid/polysulfone-amide (PMIA/PSA) composite nanofibrous filtration membrane is prepared via solution electrospinning for the development of high-temperature-resistant filtering products. To maximize the merits of each component, PMIA/PSA composite nanofibrous membranes with different mass blending ratios are prepared to determine the optimal balance. It is found that the PMIA/PSA composite nanofibrous membranes show excellent thermal stability and thermal shrinkage performance. They also maintain superb mechanical retention ratios after 200 h treatment at 200 °C. In addition, they exhibit excellent removal efficiency of polystyrene aerosol (PSL) particles of various sizes. It is found that the removal efficiency of PMIA/PSA (3/7) is 96.7% for 0.1 µm, 98.3% for 0.2 µm and 99.6% for 0.3 µm particles and it possesses optimal filtration resistance (79 Pa), while other composite membranes can reach a removal efficiency of over 99.7%. Our experimental results illustrate that the filtration efficiency for PM2.5 of PMIA/PSA (7/3), (5/5) composite nanofibrous membranes is still kept as high as 99.9% even after being treated at 200 °C for 120 h. It indicates that the prepared composite nanofibrous membranes have potential for applications where high-efficiency filtration is desired, such as bag dust filters for use under high temperatures.

2.
Talanta ; 207: 120288, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594593

RESUMO

The exploration of advanced photoactive materials with fine photoelectrochemical (PEC) performance is always the hot subject in PEC bioanalysis. Herein, Mn-doped CdS nanocrystals (CdS:Mn)-sensitized 2D/2D heterostructured g-C3N4-MoS2 was prepared and served as photoactive matrix of PEC sensing platform for myoglobin (Myo) detection using CuO nanoparticles labeled anti-Myo (anti-Myo-CuO) conjugates as signal amplification tags. The heterostructured g-C3N4-MoS2 could effectively promote the electron transfer and evidently restrain the recombination of electron-hole pairs, producing the high photocurrent response. Upon loaded CdS:Mn on the heterostructured g-C3N4-MoS2 to form co-sensitized structure, the photocurrent further gives a dramatically increase. To proof the performance of the co-sensitized structure in PEC bioanalysis, a sandwich type PEC immunosensor was designed by using the co-sensitized structure as photomatrix, Myo as model protein, and anti-Myo-CuO conjugates as amplifying tags. The introduction of anti-Myo-CuO conjugates in this system could significantly quench the PEC response of the sensing interface owing to the competition of the light-generated electron, poor conductivity and steric hindrance of the anti-Myo-CuO conjugates. In virtue of synergistic amplification of the CdS:Mn sensitized heterostructured g-C3N4-MoS2 and the anti-Myo-CuO conjugates, the immunosensor could respond down to 0.42 pg mL-1 Myo with a detectable range of 1.0 pg mL-1 to 50 ng mL-1. Moreover, this PEC platform demonstrates high specificity and sensitivity for Myo detection in real biological matrices. This strategy may furnish new insights for applications of novel 2D/2D heterostructures in PEC bioanalysis.

3.
Toxins (Basel) ; 11(11)2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671876

RESUMO

Fusarium graminearum causes Fusarium head blight (FHB), a devastating disease of wheat. Salicylic acid (SA) is involved in the resistance of wheat to F. graminearum. Cell wall mannoprotein (CWM) is known to trigger defense responses in plants, but its role in the pathogenicity of F. graminearum remains unclear. Here, we characterized FgCWM1 (FG05_11315), encoding a CWM in F. graminearum. FgCWM1 was highly expressed in wheat spikes by 24 h after initial inoculation and was upregulated by SA. Disruption of FgCWM1 (ΔFgCWM1) reduced mannose and protein accumulation in the fungal cell wall, especially under SA treatment, and resulted in defective fungal cell walls, leading to increased fungal sensitivity to SA. The positive role of FgCWM1 in mannose and protein accumulation was confirmed by its expression in Saccharomyces cerevisiae. Compared with wild type (WT), ΔFgCWM1 exhibited reduced pathogenicity toward wheat, but it produced the same amount of deoxynivalenol both in culture and in spikes. Complementation of ΔFgCWM1 with FgCWM1 restored the WT phenotype. Localization analyses revealed that FgCWM1 was distributed on the cell wall, consistent with its structural role. Thus, FgCWM1 encodes a CWM protein that plays an important role in the cell wall integrity and pathogenicity of F. graminearum.

4.
Lancet Oncol ; 20(11): e619-e626, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31674320

RESUMO

As a result of recent, substantial capacity building, a new landscape for cancer drug trials is emerging in China. However, data on the characteristics of cancer drug trials, and how they have changed over time, are scarce. Based on clinical trials published on the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, we aimed to systematically review changes over time in clinical trials of cancer drugs in mainland China from 2009 to 2018, to provide insight on the effectiveness of the pharmaceutical industry and identify unmet clinical needs of stakeholders. A total of 1493 trials of 751 newly tested cancer drugs were initiated. Increases over time were observed for the annual number of initiated trials, newly tested drugs, and newly added leading clinical trial units, with a sharp increase after 2016. Of the 1385 trials in which cancer types were identified, solid tumours (325 [23%] trials), non-small-cell lung cancer (232 [17%]), and lymphoma (126 [9%]) were the most common. A markedly uneven distribution was also observed in the geography of leading units with the largest number of leading units located in east China (50 [41%]) and the smallest number located in southwest China (4 [3%]). The growth trends we observed illustrate the progress in and increasing capability of cancer drug research and development achieved in mainland China over the decade from 2009. The low number of clinical trials on tumours with epidemiological characteristics unique to the Chinese population and the unbalanced geographical distribution of leading clinical trial units will provide potential targets for policy makers and other stakeholders. Further research efforts should address cancers uniquely relevant to Chinese populations, globally rare cancers, and the balance between equitable drug access, efficiency, and sustainability of cancer drug research and development in mainland China.

5.
Opt Express ; 27(19): 26569-26578, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31674535

RESUMO

Terahertz plasmon emission is the key to getting terahertz radiation, which has resulted in numerous studies on it. In this paper, we present the results of a theoretical investigation of terahertz plasmon emission by drifting electrons in a grated graphene system driven by an electric field by applying the Boltzmann's equilibrium equation method. The results show that plasmon frequencies from terahertz to infrared are generated by drifting electrons through the interaction between plasmons and electrons. Obvious increase of the plasmon emission strength with the driving electric field can be seen when the electric field is more than a certain strength (e.g. 1.0 kV/cm). The effects of electron density and the grating period on the emission strength of plasmons were also investigated. It was found that terahertz plasmons can be obtained by applying a grating with appropriate period. The plasmon frequencies can be tuned using either the driving electric field or the electron density controlled by the gate voltage or the grating parameters. This work may help to gain insight into graphene plasmonics and be pertinent to the application of graphene-based structures as electrically tunable terahertz plasmonic devices.

6.
Life Sci ; : 116868, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682847

RESUMO

BACKGROUND: Sepsis is an inflammatory response undergoing the complicate pathophysiological changes for host defense against pathogens. Previous studies suggested that dexmedetomidine (DEX) was served to controlling the over-reactive inflammatory effects to protect from the sepsis-induced organ failure via modulating histone methylation. However, the genome-wide changes of histone methylations upon DEX for sepsis treatment were poorly explored. MATERIALS AND METHODS: The acute kidney injury (AKI) mouse model were induced by lipopolysaccharide (LPS). DEX and KDM5 (H3K4 demethylases) inhibitors were used to add additionally. H3K4me3 antibody was used to conduct the ChIP-seq assay in renal cortex tissues. RESULTS: We observed that the overall H3K4me3 levels were obviously declined in AKI group compared to the normal control. We further observed that the therapeutic effect of DEX was basically equal with CPI-455 and KDM5A-IN-1 but better than PBIT. The overall H3K4me3 level was reduced in AKI group compared to DEX (p = 0.008), and KDM5A-IN-1 groups (p = 0.022). The H3K4me3 enrichment of the multiple genes associated with inflammatory cytokines such as TNF-α, NOS2 and CCL2 increased in AKI model, but decreased upon DEX or KDM5A-IN-1 treatment. Consistently, transcription and protein levels of genes such as TLR4, MYD88, MTA1, PTGS2, CASP3 associated with NF-κB signaling pathway were all compromising after treated with DEX or KDM5A-IN-1 groups compared to AKI group. CONCLUSION: Taken together, our data determined that DEX could attenuate AKI through KDM5A inhibition in sepsis.

7.
Opt Express ; 27(21): 29547-29557, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684214

RESUMO

Flexible electronics, as a futuristic technology, is presenting tremendous impact in areas of wearable displaying, energy saving, and adaptive camouflage. In this work, we constructed a simple triple-layered electrochemical device with high flexibility using the electroplated nickel (Ni) grid electrode and the multifunctional hydrogel. The Ni grid electrode with low resistance (0.5 Ω/sq), high optical transparency (84.8%) and good mechanical flexibility, is beneficial for efficient electron injection, while the transparent lithium chloride hydrogel functions simultaneously for ion storage, ion transportation and counter-conducting. The thin polymer poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS) film is utilized as the electrochromic (EC) material and it also distributes the electrons evenly for uniform coloration. The triple-layered EC architecture not only simplifies the manufacturing procedures but also improves the device performance in terms of optical contrast and mechanical robustness. The device shows fast response for coloration and bleaching with an absolute transmittance contrast of 40% and a contrast retention over 72% after 2500 bending cycles. The ability of the flexible electrochromic device for conformable attaching was also investigated without obvious performance degradation. The electroplated Ni grid electrode and the multifunctional hydrogel are advantageous in constructing flexible electrochromic devices in terms of the response time, the working stability and the bending capability, paving a way for next-generation flexible electronics.

8.
Opt Express ; 27(20): 28214-28222, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684578

RESUMO

Real-time detection of the ultrafast dynamics in complex nonlinear optical systems provides novel insights into pulse interactions and dynamic patterns, especially for soliton molecules. Herein, the concept of soliton molecule is extended to the pulsating regime, revealing the dynamical diversity of soliton molecule and the universality of pulsating behavior. By virtue of the dispersive Fourier transform (DFT) technique, we present the first experimental observation of the dissociation dynamics within a pulsating soliton molecule generated in an L-band normal-dispersion mode-locked fiber laser. The results provide valuable references for resolving the interactions in complex dissipative systems.

9.
Biotechnol Adv ; : 107465, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31689470

RESUMO

ß-Galactosidases, an important class of glycosidases, naturally catalyze the hydrolysis of ß-galactosidic bonds in oligosaccharides and polysaccharides. Traditionally, these enzymes have been used to degrade lactose in dairy products, which are beneficial for lactose-intolerant people. Attractively, ß-galactosidases exhibit glycosyl transfer activity under certain conditions in vitro. They are capable of synthesizing carbohydrates from cheap starting substrates in a facile, efficient, and environment-friendly way. The condensation of lactose into the well-known prebiotic galacto-oligosaccharides by ß-galactosidases has become a key aspect of the industrial interest in the synthetic activity in recent years. At present, the transglycosylation activity of these enzymes has been greatly extended. It can be used not only in building glycan blocks of crucial glycoconjugates to elucidate their biological functions, but also in glycosylation of vital molecules, which have been applied in food, medicine and cosmetic industries to improve solubility, stability and bioactivity. Further molecular engineering of ß-galactosidases has significantly improved their synthetic activity, expanded the substrate spectrum and made them more powerful in carbohydrate synthesis. This review covers the classification, structure and mechanism of ß-galactosidases, galactosylation reactions catalyzed by these enzymes, and various strategies of enzyme engineering, with an emphasis on recent advances.

10.
Medicine (Baltimore) ; 98(44): e17719, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689809

RESUMO

INTRODUCTION: Mixed urinary incontinence (MUI) is a coexistence of both urgency urinary incontinence and stress urinary incontinence. Medical, Epidemiologic, and Social aspects of Aging (MESA) questionnaire is a validated and commonly used tool to diagnose predominant components of it and assess the severity, which can offer help in clinic. However, MESA questionnaire is still not available in China. The aim of the study is to translate English MESA questionnaire into a Chinese version, adapt it in Chinese culture, and validate the measurement properties among female patients with MUI and urgency-predominant MUI. METHODS: MESA questionnaire will be translated and culturally adapted in China. The validation will be embedded in a multicentered randomized controlled trial targeted at women with urgency-predominant MUI. Apart from MESA questionnaire, 3 groups of patients are to receive clinical extended assessment, keep 3-day voiding diary, and complete International Consultation on Incontinence Questionnaire Short Form to evaluate the measurement properties of reliability and validity (internal consistence, test-retest reliability, construct validity, and responsiveness). DISCUSSION: If MESA questionnaire is of relatively high reliability and validity in diagnosing subtypes of MUI and assessing the severity, it can help to choose more appropriate therapy for patients and simplify the workload of clinicians. TRIAL REGISTRATION: ClinicalTrials.gov NCT03803878, January 11, 2019.

11.
Medicine (Baltimore) ; 98(44): e17779, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689844

RESUMO

RATIONALE: Absence or hypoplasia of the internal carotid artery (ICA) are rare developmental anomalies. Usually, patients with ICA agenesis are asymptomatic due to collateral circulation, but they may present with seizures, headache, or transient ischemic attack. We report a patient with right ICA absence in whom "paroxysmal right eye amaurosis" was the main symptom. PATIENT CONCERNS: A 76-year-old male patient suffered from "paroxysmal right eye amaurosis for 3 years". Three years prior, the patient had suffered sudden one-minute right eye amaurosis without any obvious cause. The attack reoccurred 1-2 times/year until one week before admission when he experienced two sudden right eye amaurosis. DIAGNOSIS: Congenital absence of the right ICA was diagnosed. In this patient with congenital absence of the right ICA, the ipsilateral anterior cerebral artery (ACA) was compensated by the anterior communicating artery (ACOM), and the ipsilateral middle cerebral artery (MCA) emerged from the carotid siphon of the contralateral ICA. INTERVENTIONS: The patient was given antiplatelet treatment consisting of aspirin and atorvastatin after admission and instructed to maintain the treatment after discharge. OUTCOMES: No symptom onset was observed during follow-up. LESSONS: Here, we report the patient's clinical manifestations and imaging findings and analyze the cause of the condition to provide a clinical reference for the study of congenital absence of the ICA.

12.
Hemoglobin ; : 1-4, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690131

RESUMO

Although mutations causing α-thalassemia (α-thal) are mainly larger deletions involving one or both of the duplicated α-globin genes, point mutations are not rare. We have identified a novel mutation of the translation initiation codon of the α2-globin gene with DNA sequencing and allele-specific multiplex ligation-dependent probe amplification (MLPA) in a Chinese family. RNA analysis was performed with reverse transcription-MLPA (RT-MLPA). A novel mutation at the translation initiation codon of the α2-globin gene (HBA2: c.3G>C) was identified. The proband and his father, who were both carriers of this mutation, had a hematological phenotype of mild α+-thalassemia (α+-thal) trait with low-normal limit of mean corpuscular volume (MCV) and normal Hb A2. RNA analysis showed markedly decreased levels of α-globin mRNA and the presence of a small amount of mutant mRNA. The HBA2: c.3G>C mutation most likely caused α-thal by lowering levels of wild α-globin chain. Our study increases the mutation spectrum of α-thal.

13.
Chem Commun (Camb) ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31690892

RESUMO

A putrescine derivative of aminomethyladamantane is established as a ditopic guest with two mutually exclusive binding sites for cucurbit[6]uril and cucurbit[7]uril. A mixture containing both hosts, the ditopic guest, and two fluorescent dyes affords a relay system with a ratiometric fluorescence response and enables a kinetic analysis of the switching mechanism.

14.
Br J Pharmacol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670839

RESUMO

BACKGROUND AND PURPOSE: Hepatic CYP450s play an important role in drug-induced hepatotoxicity. They are altered not only in liver diseases but in many non-liver diseases, such as extra-hepatic tumours. Consequently, CYP450-mediated abnormal drug exposure increases the incidence and extent of hepatotoxicity. However, people often underestimate this risk because the mechanisms underlying hepatic CYP450s reduction in extra-hepatic tumours remain unclear. EXPERIMENTAL APPROACH: To avoid additional influences of chemical carcinogenesis inducers used in spontaneous tumour mouse models on hepatic CYP450s, we chose mice with subcutaneously transplanted tumours to model extra-hepatic tumours. CYP3A reduction was evaluated by qPCR, western blotting and metabolic activity. LC-Q/TOF-MS and GC-MS were used in combination for analysing liver metabolomics. The contribution of pentose phosphate pathway (PPP) to CYP3A reduction was investigated by chemical interfering and silencing of glucose-6-phosphate dehydrogenase. KEY RESULTS: CYP3A was already inhibited at the early stage of tumour growth when no significant inflammatory response was observed yet. The PPP was predominately disrupted at this non-inflammatory stage. On one hand, the disrupted PPP directly inhibited CYP3A through chk2/p53/p65 pathway at the non-inflammatory stage; on the other hand, it indirectly strengthened the subsequent IL-6-mediated CYP3A reduction at the inflammatory stage. Through PPP recovery with menadione in the non-inflammatory stage, CYP3A reduction could be reversed, which was comparable to that of IL-6 inhibitor tocilizumab. This PPP modulation strategy to alleviate CYP3A-mediated drug hepatotoxicity was validated with dasatinib in vivo. CONCLUSIONS AND IMPLICATIONS: PPP modulation at the non-inflammatory stage might provide a novel and distinctive approach to manage CYP3A-mediated drug hepatotoxicity.

15.
Br J Nutr ; : 1-20, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31699171

RESUMO

Maintenance hemodialysis (MHD) is the use of a machine to filter wastes, salts and fluid from blood for at least 3 months to prolong the life of patients with advanced kidney failure. Although low dietary energy intake (DEI) has been observed in MHD patients, few studies have related DEI to the risk of mortality. To explore this relationship, a study included 1039 MHD patients from 8 centers was conducted. DEI was assessed by three 24-hour diet recalls including one dialysis day and two non-dialysis days, and was normalized to ideal body weight (IBW). All-cause mortality and CVD mortality were the primary and secondary outcomes, respectively. During a median follow-up of 28 months, all-cause and CVD mortality occurred in 230 (22.1%) and 140 (13.5%) participants. Overall, a U-shaped relationship was observed between DEI and all-cause or CVD mortality. The risk of all-cause mortality decreased significantly with the increase of DEI in participants with DEI <40kcal/kg IBW/d (HR, 0.98; 95% CI: 0.96-1.00) and increased significantly with the increase of DEI in those with DEI ≥40kcal/kg IBW/d (HR, 1.12; 95%CI: 1.04-1.20). Similarly, the risk of CVD mortality decreased with the increase of DEI in participants with DEI <36.5kcal/kg IBW/d (HR, 0.96; 95%CI: 0.93-0.99) and increased with the increase of DEI in participants with DEI ≥36.5kcal/kg IBW/d (HR, 1.11; 95%CI: 1.04-1.18). In summary, there was a U-shaped association between DEI and all-cause or CVD mortality, with a turning point at about 40 and 36.5 kcal/kg IBW/d, respectively, in MHD patients.

16.
Inorg Chem ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680517

RESUMO

Hydro(solvo)thermal syntheses of quaternary copper sulfides containing alkaline earth metal ions remain a great challenge because of the low solubility of Cu-S compounds. Herein, a new facile solvothermal method was developed, and four quaternary copper sulfides, i.e., BaCu3InS4 (1), BaCu3GaS4 (2), BaCu2SnS4 (3), and BaCu2GeS4 (4), were prepared using excess sulfur as a mineralizer. Compound 1 possesses a novel three-dimensional (3D) anionic [Cu3InS4]2- framework constructed by an 8-membered ring of [Cu4S4] and [Cu2In2S4] alternatively. Compound 2 features a unique 3D anionic [Cu3GaS4]2- framework composed of [Cu3GaS10]n14n- anionic chains and 8-membered rings, in which [Cu4S4] and [Cu2Ga2S4] reside alternatively. Compounds 3 and 4 feature 3D anionic [Cu2MS4]2- (M = Sn, Ge) frameworks composed of CuS4 and MS4 tetrahedra with Ba2+ located in the channels. It is worth noting that different 3D Cu-S frameworks exist in the title crystal structures, in which main group ions are incorporated. This paper provides a new synthetic strategy for new quaternary sulfides.

17.
Nat Prod Res ; : 1-8, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680553

RESUMO

Two new norsesquiterpenoids, dioscopposin A (1) and dioscopposin B (2), as well as 21 known compounds (3-23) were isolated from the stems and leaves of Dioscorea oppositifolia L. Their structures were elucidated by detailed analysis of comprehensive spectroscopic data. The absolute configurations were deduced by the comparison of experimental and calculated electronic circular dichroism spectra. Estrogenic activity of all the isolated compounds were evaluated using MCF-7 cells proliferation assay and compounds 2, 3, 7, 13, 15, 16, 18 and 21 exhibited proliferation activity.

18.
Nanoscale ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31681915

RESUMO

The intestinal epithelium is the main barrier for nanocarriers to orally deliver poorly water-soluble and absorbed agents. To further improve the transmembrane transport efficiency of polymeric micelles, intestinal oligopeptide transporter PepT1-targeted polymeric micelles were fabricated by Gly-Sar-conjugated poly(ethylene glycol)-poly(d,l-lactic acid). The functionalized polymeric micelles with about 40 nm diameter, uniform spherical morphology and favorable cytocompatibility with Caco-2 cells were demonstrated to distinctly enhance the cellular uptake and transmembrane transport of the loaded agents. The results of intestinal absorption strongly evidenced the higher accumulation of the micelles inside the epithelial cells, at the apical and basolateral sides of the epithelium within the villi in mice. Furthermore, the interaction of Gly-Sar decorated polymeric micelles with PepT1 was explored to promote the internalization of the micelles through fluorescence immunoassay, and the PepT1 level on the membrane of Caco-2 cells treated with the micelles appeared to change in a distinctly time-dependent manner. Both clathrin- and caveolae-mediated pathways were involved in the transcellular transport for undecorated polymeric micelles, while the transcellular transport pathway for Gly-Sar decorated ones was changed to be mainly mediated by clathrin and lipid rafts. The colocalization of Gly-Sar decorated micelles with the organelles observed by confocal laser scanning microscopy indicated that late endosomes, lysosomes, endoplasmic reticulum and Golgi apparatus appeared to participate in the intracellular trafficking progression of the micelles. These results suggested that PepT1-targeted polymeric micelles might have a strong potential to greatly promote the oral absorption of poorly water-soluble and absorbed agents.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31682098

RESUMO

Acute myocardial infarction (AMI) is one of the leading causes of death around the world. An early and accurate diagnosis of AMI is critical to reduce the mortality rate. As an important cardiac biomarker, Creatine kinase (CK) has been used in clinical diagnosis of AMI. However, it still remains a great challenge to realize highly sensitive and selective CK detection in blood specimen. Herein we have developed an ultrasensitive platform for detection of CK activity based on time-resolved (TR) luminescent lanthanide metal-organic framework nanoprobes (Eu-QPTCA). Benefiting from the intense emission of lanthanide ions sensitizated by the organic ligands and the eliminated short-lived autofluorescence by TR technique, these nanoprobes enabled homogeneous detection of CK activity with a limit of detection down to 1.0 U/L, which is about one order of magnitude improvement relative to that of the traditional methods. In addition, the Eu-QPTCA nanoprobes showed superior selectivity and reliability toward practical detection of CK activity in human serum, indicating great significance of our method in early diagnosis of AMI. We envision that the proposed bioassay strategy can be extended to the detection of other phosphorylation enzymes, paving a way for promising applications in clinical diagnostics.

20.
J Photochem Photobiol B ; 200: 111645, 2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31671371

RESUMO

Antimicrobial peptide W3R6 was derived from chensinin-1b and showed potential as a novel antibiotics. However, W3R6 was susceptible to protease cleavage, which limited its therapeutic application. To improve the proteolytic resistance of W3R6, D-amino acids were incorporated into its sequence by specific amino acid substitution or whole sequence substitution according to the specificity of the cleavage site. In this study, partially substituted analog D-Arg-W3R6 and completely substituted D-enantiomer D-W3R6 were synthesized. The resistance of D-Arg-W3R6 and D-W3R6 to cleavage by the tested protease increased, particularly of D-W3R6. The antimicrobial activity of D-Arg-W3R6 was almost the same as that of the parent peptide W3R6, but the antimicrobial activity of D-W3R6 was slightly decreased. The hemolytic activity of both D-Arg-W3R6 and D-W3R6 was negligible. The CD spectrum of D-W3R6 exhibited symmetry with that of W3R6 in a membrane-mimetic environment. The membrane interaction between the D-amino acid substituted analogs and a real/mimic bacterial cell membrane was examined. The outer membrane depolarization, inner membrane permeability and dye leakage in three types of liposomes treated with D-Arg-W3R6 and D-W3R6 were not obviously different from W3R6, which could be due to the similar physical and chemical properties. In addition, these three peptides showed the binding ability with LPS micelles detected by ITC, and their ability to disrupt the LPS micelles was examined by DLS experiment and even neutralize the surface negative charge of E. coli cells. These results suggest that D-Arg-W3R6 is a promising antibiotic molecule.

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