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1.
Biotechnol Bioeng ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32175589

RESUMO

Beyond their widespread application as genome-editing and regulatory tools, CRISPR-Cas systems also play a critical role in nucleic acid detection due to their high sensitivity and specificity. Recently developed Cas family effectors have opened the door to the development of new strategies for detecting different types of nucleic acids with a variety of purposes. Precise and efficient nucleic acid detection using CRISPR-Cas systems has the potential to advance both basic and applied biological research. In this review, we summarize the CRISPR-Cas systems used for the recognition and detection of specific nucleic acids for different purposes, including the detection of genomic DNA, nongenomic DNA, RNA and pathogenic microbe genomes. Current challenges and further applications of CRISPR-based detection methods will be discussed according to the most recent developments. This article is protected by copyright. All rights reserved.

2.
Pol J Microbiol ; 69: 1-11, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32067441

RESUMO

Daqu made from raw wheat, barley or pea is used as an inoculum for the fermentation of Chinese Baijiu. In this study, the microbial communities of four different types of Daqus (sauce-flavor Wuling Daqu, sauce and strong-flavor Baisha Daqu, strong-flavor Deshan Daqu, and light-flavor Niulanshan Daqu) were analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), phospholipid fatty acid (PLFA) analysis, and Biolog EcoPlates analysis (Biolog). Clear differences were seen between the microbial communities of the four Daqus. PCR-DGGE showed differences in the number and brightness of bands between the Daqus, indicating the presence of unique bacterial species in Deshan Daqu, Wuling Daqu, and Niulanshan Daqu. Lactobacillus sanfranciscensis, Bacillus thermoamylovorans, and some unclassified bacteria were unique to Wuling Daqu, Deshan Daqu, and Niulanshan Daqu, respectively. Moreover, some bacterial species were observed in all four Daqus. A total of 26 PLFAs between C12 to C20 were detected from the four Daqus by PLFA analysis. Wuling Daqu had the highest total and fungal biomasses, Baisha Daqu had the highest bacterial biomass, and Niulanshan Daqu had the highest ratio of fungal biomass to bacterial biomass. The Biolog results indicated differences in the carbon source use and mode of the four Daqus, and also demonstrated that each Daqu had varying abilities to utilize different types of carbon sources. The cluster analysis of the three methods showed that the microbial communities of the four Daqus were different. This study also demonstrates the applicability of the three analytical methods in the evaluating of the microbial communities of Daqus.Daqu made from raw wheat, barley or pea is used as an inoculum for the fermentation of Chinese Baijiu. In this study, the microbial communities of four different types of Daqus (sauce-flavor Wuling Daqu, sauce and strong-flavor Baisha Daqu, strong-flavor Deshan Daqu, and light-flavor Niulanshan Daqu) were analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), phospholipid fatty acid (PLFA) analysis, and Biolog EcoPlates analysis (Biolog). Clear differences were seen between the microbial communities of the four Daqus. PCR-DGGE showed differences in the number and brightness of bands between the Daqus, indicating the presence of unique bacterial species in Deshan Daqu, Wuling Daqu, and Niulanshan Daqu. Lactobacillus sanfranciscensis, Bacillus thermoamylovorans, and some unclassified bacteria were unique to Wuling Daqu, Deshan Daqu, and Niulanshan Daqu, respectively. Moreover, some bacterial species were observed in all four Daqus. A total of 26 PLFAs between C12 to C20 were detected from the four Daqus by PLFA analysis. Wuling Daqu had the highest total and fungal biomasses, Baisha Daqu had the highest bacterial biomass, and Niulanshan Daqu had the highest ratio of fungal biomass to bacterial biomass. The Biolog results indicated differences in the carbon source use and mode of the four Daqus, and also demonstrated that each Daqu had varying abilities to utilize different types of carbon sources. The cluster analysis of the three methods showed that the microbial communities of the four Daqus were different. This study also demonstrates the applicability of the three analytical methods in the evaluating of the microbial communities of Daqus.

3.
J Biol Chem ; 295(9): 2760-2770, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-31941790

RESUMO

The calcineurin/nuclear factor of activated T cell (CN/NFAT) signaling pathway plays a critical role in the immune response. Therefore, inhibition of the CN/NFAT pathway is an important target for inflammatory disease. The conserved PXIXIT and LXVP motifs of CN substrates and targeting proteins have been recognized. Based on the affinity ability and inhibitory effect of these docking sequences on CN, we designed a bioactive peptide (named pep3) against the CN/NFAT interaction, which has two binding sites derived from the RCAN1-PXIXIT motif and the NFATc1-LXVP motif. The shortest linker between the two binding sites in pep3 is derived from A238L, a physiological binding partner of CN. Microscale thermophoresis revealed that pep3 has two docking sites on CN. Pep3 also has the most potent inhibitory effect on CN. It is suggested that pep3 contains an NFATc1-LXVP-substrate recognition motif and RCAN1-PXIXIT-mediated anchoring to CN. Expression of this peptide significantly suppresses CN/NFAT signaling. Cell-permeable 11-arginine-modified pep3 (11R-pep3) blocks the NFAT downstream signaling pathway. Intranasal administration of the 11R-pep3 peptide inhibits airway inflammation in an ovalbumin-induced asthma model. Our results suggest that pep3 is promising as an immunosuppressive agent and can be used in topical remedies.

4.
Water Sci Technol ; 80(4): 784-793, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31661457

RESUMO

Coconut shell biochar (CSB) was selected as raw material to obtain two kinds of modified biochars by pickling and iron modification. The pickling coconut shell biochar (PCSB) and pickling-iron modified coconut shell biochar (PICSB) were used as adsorbents to remove NO3-N in alkaline rare earth industry effluent. The results showed that pickling smoothed the surface of CSB, and α-FeOOH was formed on the surface of PCSB because of FeCl3 solution modification. Suitable adsorbent dosages of PCSB and PICSB were both 2.0 g/L. The NO3-N adsorption process by PCSB and PICSB both reached equilibrium at 30 min. The quasi-first-order kinetic model shows good fit to the NO3-N adsorption by PCSB. Whereas, the quasi-second-order kinetic model is more suitable for PICSB adsorbing NO3-N. The adsorption mechanisms of PICSB for NO3-N removal were ligand exchange and electrostatic attraction, and that of PCSB for NO3-N removal was electrostatic attraction. The NO3-N adsorption amounts of PCSB and PICSB decreased with increasing adsorption temperature and pH. The maximum NO3-N adsorption amounts of PCSB and PICSB were 15.14 mg/L and 10.75 mg/L respectively with adsorbent dosage of 2.0 g/L, adsorption time of 30 min, adsorption temperature of 25 ± 1 °C, and initial solution pH of 2.01.


Assuntos
Cocos , Poluentes Químicos da Água , Adsorção , Carvão Vegetal
5.
Chem Asian J ; 14(23): 4246-4254, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31571387

RESUMO

A new coordination polymer (H2 bpy)0.5 ⋅[(UO2 )1.5 (ipa)2 (H2 O)] (1) (H2 ipa=isophthalic acid, bpy=4,4'-bipyridine) was synthesized by hydrothermal condition. It was characterized by IR spectroscopy, elemental analysis, TG-DTA analysis, and powder X-ray diffraction. Analysis of single-crystal X-ray diffraction results showed that the title compound exhibited a double chain bridged by the different uranyl ions and ipa2- ligands. Through the hydrogen bond interactions and π⋅⋅⋅π stacking interactions, the double chains were assembled into the three-dimensional supramolecular framework. Furthermore, the compound can be used as a promising bifunctional luminescence sensor for detecting and identifying Fe3+ and tetracycline hydrochloride antibiotic molecules with high selectivity and sensitivity in aqueous solutions. Moreover, the luminescent sensing mechanisms for different analytes were proposed. Moreover, the electronic properties of title compound were explored by density functional theory (DFT) calculations. The sensor system has been successfully applied for the detection of Fe3+ and tetracycline hydrochloride with high recovery percentages and low relative standard deviation in real river water samples.


Assuntos
Compostos Férricos/análise , Corantes Fluorescentes/química , Estruturas Metalorgânicas/química , Tetraciclina/análise , Água/química , Ligantes , Polímeros/química , Teoria Quântica , Espectrometria de Fluorescência , Compostos de Urânio/química
6.
Chem Rec ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31631504

RESUMO

Heterogeneous catalysis plays a key role in promoting green chemistry through many routes. The functionalizable reactive silanols highlight silica as a beguiling support for the preparation of heterogeneous catalysts. Metal active sites anchored on functionalized silica (FS) usually demonstrate the better dispersion and stability due to their firm chemical interaction with FSs. Having certain functional groups in structure, FSs can act as the useful catalysts for few organic reactions even without the need of metal active sites which are termed as the covetous reusable organocatalysts. Magnetic FSs have laid the platform where the effortless recovery of catalysts is realized just using an external magnet, resulting in the simplified reaction procedure. Using FSs of multiple functional groups, we can envisage the shortened reaction pathway and, reduced chemical uses and chemical wastes. Unstable bio-molecules like enzymes have been stabilized when they get chemically anchored on FSs. The resultant solid bio-catalysts exhibited very good reusability in many catalytic reactions. Getting provoked from the green chemistry aspects and benefits of FS-based catalysts, we confer the recent literature and progress focusing on the significance of FSs in heterogeneous catalysis. This review covers the preparative methods, types and catalytic applications of FSs. A special emphasis is given to the metal-free FS catalysts, multiple FS-based catalysts and magnetic FSs. Through this review, we presume that the contribution of FSs to green chemistry can be well understood. The future perspective of FSs and the improvements still required for implementing FS-based catalysts in practical applications have been narrated at the end of this review.

7.
Analyst ; 144(20): 6041-6047, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31508616

RESUMO

In the present study, four copper-based metal-organic frameworks were facilely prepared to study the effects of the substituent groups of the ligand on the enzyme-like properties of these frameworks. It was found that all of them were capable of catalyzing the reaction between 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2; this demonstrated their enzyme-like properties. Moreover, the enzyme-like catalytic properties of all the Cu-MOFs obtained herein were studied in detail. Interestingly, the results indicate that the four Cu-MOFs should be addressed as different enzyme mimics although the chemical structures of their ligands are quite similar. Among these four MOFs, the Cu-MOF with the -NO2 group (Cu-MOF (ii)) exhibits highest catalytic activity at neutral pH, which would be beneficial for its application in real biological samples. Moreover, its catalytic activity should be ascribed to the generation of oxygen induced by Cu-MOF (ii)-catalyzed H2O2 decomposition; this accordingly indicates that this MOF should be called a catalase mimic. Under optimized conditions, the Cu-MOF (ii) was applied to develop a (GSH) colorimetric assay for glutathione (GSH). In addition, GSH detection in serum was performed, and satisfactory results were obtained. Therefore, a simple, sensitive and selective colorimetric assay based on the MOF catalase mimic for the detection of GSH was developed.


Assuntos
Materiais Biomiméticos/química , Técnicas Biossensoriais/métodos , Catalase/química , Cobre/química , Glutationa/sangue , Estruturas Metalorgânicas/química , Nitrocompostos/química , Catálise , Humanos
8.
Lab Chip ; 19(17): 2936-2946, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31380864

RESUMO

It is becoming more difficult to use bulk mixing and bi-fluid micromixing in multi-step continuous-flow reactions, multicomponent reactions, and nanoparticle synthesis because they typically involve multiple reactants. To date, most micromixing studies, both passive and active, have focused on how to efficiently mix two fluids, while micromixing of three or more fluids together (multi-fluid mixing) has been rarely explored. This study is the first on tri-fluid mixing in microchannels. We investigated tri-fluid mixing in three microchannel models: a straight channel, a classical staggered herringbone mixing (SHM) channel, and a three-dimensional (3D) X-crossing microchannel. Numerical simulations and experiments were jointly conducted. A two-step experimental process was performed to determine the tri-fluid mixing efficiencies of these microchannels. We found that the SHM cannot significantly enhance mixing of three streams especially for a Reynolds number (Re) higher than 10. However, the 3D X-crossing channel based on splitting-and-recombination (SAR) showed effective tri-mixing performance over a wide Re range up to 275 (with a corresponding flow rate of 1972.5 µL min-1), thereby enabling high microchannel throughput. Furthermore, this tri-fluid micromixing process was used to synthesize a kind of Si-based nanoparticle. This achieved a narrower particle size distribution than traditional bulk mixing. Therefore, SAR-based tri-fluid mixing is an alternative for chemical and biochemical reactions where three reactants need to be mixed.

9.
Biotechnol Lett ; 41(10): 1147-1154, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31428906

RESUMO

OBJECTIVES: Developing a dynamic regulation strategy is an essential step in establishing an automatic control system for manipulating metabolic fluxes and cellular behaviors. To broaden the extent of the application, a system that can generally control any gene of interest is demanded. RESULTS: Through characterization and optimization, the strategy repressed the immediate expression incrementally from 0 to 90% during culturing. Moreover, by changing single base pair in the lux box of the Plux promoter, the degree of repression of the target genomic gene was tuned to a difference of 70%. This strategy is expected to control metabolic flux without disrupting cell growth. CONCLUSIONS: We engineered bacterial small RNA to develop a pathway-independent strategy that can dynamically repress the expression of any gene at the posttranscription level.


Assuntos
Escherichia coli/genética , Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Percepção de Quorum , RNA Bacteriano/biossíntese , Pequeno RNA não Traduzido/biossíntese
10.
Sci Total Environ ; 690: 654-666, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31301506

RESUMO

Potassium monopersulfate (PMS) without a catalyst as cathode electron acceptor was first established to improve the electricity generation performance of a microbial fuel cell (MFC) in this study. The work investigated the performance with pure PMS (PPMS) and compound PMS (CPMS). The concentration and initial pH of PMS had an effect on the electricity generation, which increased with higher PMS concentration and lower catholyte pH. In the PPMS-MFC system, the maximum voltage (0.972 V), power density (16.37 W/m3), optimal exchange current density (2.000 A/m3) and minimum polarization impedance (Rp: 97.33 Ω) were reached at 10 mM PMS and pH 3.0. However, the maximum power density (8.60 W/m3) was exhibited at 70 mM PMS and pH 3.0 in the CPMS system. Additionally, high COD removals of 99.41% and 98.71% in anode chambers were obtained in the two systems, respectively. Sulfate radicals (SO4-) and hydroxyl radicals (OH) played significant roles in the PPMS-MFC, while HClO was also a contributor in addition to SO4- and OH in the CPMS-MFC. Furthermore, SO4- and OH was generated in situ in the cathode to promote the reduction reaction. The inorganic anion had different effects on electricity generation. Finally, while energy was recovered, rhodamine B (RhB) was added to the cathode chamber and then removed successfully in PPMS-MFC system. This work confirmed that only PMS could be activated by bio-electrochemical method, which is an energy-saving, environmentally friendly and effective activation approach, and thus, it could be used as an efficient acceptor in a MFC.


Assuntos
Fontes de Energia Bioelétrica , Compostos de Potássio/química , Sulfatos/química , Técnicas Eletroquímicas , Eletrodos , Elétrons
11.
Anal Chem ; 91(13): 8443-8452, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31247719

RESUMO

We report a novel immunocapture (IC)-LC-MS/MS methodology to directly measure real time in vivo receptor occupancy (RO) for a covalent binding drug in blood lysate. A small molecule quencher was added immediately after sample collection to convert the free receptor to a quencher-bound receptor (QB-R) which was measured with the drug-bound receptor (DB-R) simultaneously by LC-MS/MS after immunocapture enrichment, followed by trypsin digestion. Addition of the quencher is necessary to prevent the free receptor from ex vivo binding with the drug. The real time RO was calculated based on the concentrations of DB-R and the free receptor (which is now QB-R) that were obtained from each sample. This strategy has been successfully applied to the measurement of the RO for Bruton's tyrosine kinase (BTK) in the blood lysate of monkeys after dosing with branebrutinib (BMS-986195), a covalent BTK inhibitor being evaluated to treat rheumatoid arthritis. A custom-made quencher, which is more reactive to BTK than branebrutinib, was added in excess amount to bind with all available free BTK to form quencher-bound BTK (QB-BTK) during blood sample collection. To measure a wide range of % BTK RO, including those of <5% or >95%, the required LLOQ at 0.125 nM for QB-BTK and 0.250 nM for drug-bound BTK (DB-BTK) in blood lysate were successfully achieved by using this IC-LC-MS/MS strategy. This proof-of-concept assay demonstrated its suitability with high throughput for real time in vivo BTK RO measurement as a pharmacodynamic (PD) biomarker for clinical drug development.

12.
Plant J ; 99(2): 201-215, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31134682

RESUMO

Hexaploid common wheat is one of the most important food crops worldwide. Common wheat domestication began in the Fertile Crescent of the Near East approximately 10 000 years ago and then spread west into Europe and eastward into East Asia and China. However, the possible spreading route into and within China is still unclear. In this study, we successfully extracted DNA from single ancient wheat seeds and sequenced the whole genome of seven ancient samples from Xiaohe and Gumugou cemeteries in Xinjiang, China. Genomic inference and morphological observation confirmed their identity as hexaploid common wheat grown in prehistoric China at least 3200 years before present (BP). Phylogenetic and admixture analyses with RNA-seq data of modern hexaploid wheat cultivars from both China and Western countries demonstrated a close kinship of the ancient wheat to extant common wheat landraces in southwestern China. The highly similar allelic frequencies in modern landraces of the Qinghai-Tibetan plateau with the ancient wheat support the previously suggested southwestern spreading route into highland China. A subsequent dispersal route from the Qinghai-Tibetan plateau margins to the Yangtze valley was proposed in this study. Furthermore, the common wheat populations grown in the Middle and Lower Yangtze valley wheat zones were also proposed to be established by population admixture with the wheat grown in the Upper Yangtze valley. Our study reports ancient common wheat sequences at a genome-wide scale, providing important information on the origin, dispersal, and genetic improvement under cultivation of present-day wheat landraces grown in China.

13.
Front Genet ; 10: 316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31024626

RESUMO

Tung tree (Vernicia fordii), an economically important woody oil plant, is a monoecious and diclinous species with male and female flowers on the same inflorescence. The extremely low proportion of female flowers leads to low fruit yield in tung orchards. The female flower normally develops along with stamen abortion; otherwise sterile ovules will be produced. However, little knowledge is known about the molecular basis of the female flower development in tung tree. In this study, integrated analyses of morphological and cytological observations, endogenous phytohormone assay and RNA-seq were conducted to understand the molecular mechanism of the female flower development in tung tree. Cytological observation suggested that the abortion of stamens in female flowers (SFFs) belongs to the type of programmed cell death (PCD), which was caused by tapetum degeneration at microspore mother cell stage. A total of 1,366 differentially expressed genes (DEGs) were identified in female flowers by RNA-seq analysis, of which 279 (20.42%) DEGs were significantly enriched in phenylpropanoid biosynthesis, phenylalanine metabolism, flavonoid biosynthesis, starch and sucrose metabolism, and plant hormone signal transduction. Stage-specific transcript identification detected dynamically expressed genes of important transcription regulators in female flowers that may be involved in PCD and floral organ development. Gene expression patterns revealed that 17 anther and pollen development genes and 37 PCD-related genes might be involved in the abortion of SFF. Further analyses of phytohormone levels and co-expression networks suggested that salicylic acid (SA) accumulation could trigger PCD and inhibit the development of SFF in tung tree. This study provides new insights into the role of SA in regulating the abortion of SFF to develop normal female flowers.

14.
Sci Rep ; 9(1): 5929, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30976039

RESUMO

Inflammation has been known to affect endothelial function and is involved in the progression of erectile dysfunction (ED). Thus, our present study was conducted to investigate the association between inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and ED in a Chinese male population. A total of 1515 participants with anthropometric measurements, serum analyses and hs-CRP values available were included in our cross-sectional study. Data involving socioeconomic and lifestyle factors were also collected. ED was assessed by the 5-item International Index Erectile Function (IIEF-5), and hs-CRP levels were measured by the immunoturbidimetric assay. Logistic regression was applied to estimate the association between the serum hs-CRP and the risk of ED, and receiver operating characteristics (ROC) curve analysis was performed to identify the predictive value of hs-CRP. Serum hs-CRP levels were significantly higher in ED patients, and increased progressively with the incremental severity of ED (P < 0.001 for trend). In the multivariate-adjusted model, men in the highest quartile of hs-CRP level versus those in the lowest quartile had a 50% increased likelihood for ED (OR = 1.50; 95% CI = 1.08-2.08). When subjects were stratified by age, the risk of ED was more prominently in the middle-aged and elderly men. Based on the ROC analysis, serum hs-CRP has a poor diagnostic value for ED with an AUC of 0.58 (95% CI: 0.56-0.61) but has a good diagnostic performance for differentiating severe ED (AUC: 0.79; 95% CI: 0.77-0.81). Our study indicates that increased serum hs-CRP levels are associated with the severity of ED and an increased ED risk in a Chinese male population. These findings suggest that hs-CRP may be of value as an inflammatory marker for the assessment of ED risk and may play an important role in the etiology of ED.

15.
Water Sci Technol ; 80(10): 2003-2012, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32144232

RESUMO

To remove NO3-N from water, coconut shell biochar (CSB) was modified by a solution of FeCl3, a solution of AlCl3 and a mixture solution of FeCl3 and AlCl3 respectively. The obtained modified biochar with the best effect of NO3-N adsorption was screened out to explore the adsorption behavior and mechanism of NO3-N removal by batch experiments and kinetics and thermodynamics and correlated characterization. The results indicated that the mixture solution of FeCl3- and AlCl3- modified CSB (Fe-Al/CSB) showed the best adsorption performance for NO3-N removal. Iron and aluminum elements existed on the surface of Fe-Al/CSB in the form of FeOOH, Fe2O3, Fe2+, and Al2O3 respectively. The adsorption process could reach equilibrium in 20 min. An acidic condition was favorable for NO3-N adsorption. The presence of coexisting anions was not conducive for NO3-N adsorption. The quasi-second-order model and Freundlich model could be well fitted in the adsorption process. The maximum adsorption capacity of Fe-Al/CSB fitted by the Langmuir model could reach 34.20 mg/g. The adsorption of NO3-N by Fe-Al/CSB was an endothermic and spontaneous process. Ligand exchange and chemical redox reaction were the NO3-N adsorption mechanisms which led to NO3-N adsorption by Fe-Al/CSB.


Assuntos
Poluentes Químicos da Água , Água , Adsorção , Carvão Vegetal , Cinética , Termodinâmica
16.
Protein Eng Des Sel ; 31(5): 159-171, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30247737

RESUMO

Tumor-specific delivery of cytotoxic agents remains a challenge in cancer therapy. Antibody-drug conjugates (ADC) deliver their payloads to tumor cells that overexpress specific tumor-associated antigens-but the multi-day half-life of ADC leads to high exposure even of normal, antigen-free, tissues and thus contributes to dose-limiting toxicity. Here, we present Adnectin-drug conjugates, an alternative platform for tumor-specific delivery of cytotoxic payloads. Due to their small size (10 kDa), renal filtration eliminates Adnectins from the bloodstream within minutes to hours, ensuring low exposure to normal tissues. We used an engineered cysteine to conjugate an Adnectin that binds Glypican-3, a membrane protein overexpressed in hepatocellular carcinoma, to a cytotoxic derivative of tubulysin, with the drug-to-Adnectin ratio of 1. We demonstrate specific, nanomolar binding of this Adnectin-drug conjugate to human and murine Glypican-3; its high thermostability; its localization to target-expressing tumor cells in vitro and in vivo, its fast clearance from normal tissues and its efficacy against Glypican-3-positive mouse xenograft models.


Assuntos
Glipicanas/metabolismo , Imunoconjugados/química , Neoplasias/metabolismo , Sequência de Aminoácidos , Animais , Estabilidade de Medicamentos , Feminino , Células HEK293 , Humanos , Imunoconjugados/farmacocinética , Camundongos , Distribuição Tecidual
17.
Chin J Cancer Res ; 30(3): 299-306, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30046224

RESUMO

Objective: To analyze the incidence and mortality rates of laryngeal cancer in China from 2008 to 2012. Methods: Incident and death cases of laryngeal cancer were retrieved from the National Central Cancer Registry (NCCR) database collecting from 135 cancer registries in China during 2008-2012. The crude incidence and mortality rates of laryngeal cancer were calculated by area (urban/rural), region (eastern, middle, western), gender and age group (0, 1-4, 5-9, …, 85+). China census in 2000 and Segi's world population were applied for age standardized rates. JoinPoint (Version 4.5.0.1) model was used for time trend analysis. Results: The crude incidence rate of laryngeal cancer was 1.86/100,000 ranked the 21st in overall cancers. The age-standardized incidence rates by China population (ASIRC) and by World population (ASIRW) were 1.22/100,000 and 1.23/100,000, respectively. The crude mortality of laryngeal cancer in China was 1.01/100,000 and it was the 21st cause of cancer-related death in overall cancers. Both the age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 0.63/100,000. Incidence and mortality rates of laryngeal cancer were higher in males than in females and higher in urban areas than in rural areas. Middle areas had the highest incidence and mortality rates followed by eastern and western areas. Incidence and mortality rates of laryngeal cancer retained low level before age of 40 years old but increased greatly after and peaked in age group of 75. Incidence showed significant down trends in recent 10 years by 1.27% annually [95% confidence interval (95% CI): -2.2%, -0.3%]. Mortality declined in females sharply by 5.18% per year although stable in males and both sexes combined. Conclusions: Appropriate targeted prevention, early detection and treatment programs should be carried out to control the local burden of laryngeal cancer.

18.
Anal Chem ; 90(11): 6936-6944, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29707954

RESUMO

Lipidomics is a significant way to understand the structural and functional roles that lipids play in biological systems. Although many mass spectrometry (MS)-based lipidomics strategies have recently achieve remarkable results, in vivo, in situ, and microscale lipidomics for small biological organisms and cells have not yet been obtained. In this article, we report a novel lipidomics methodology for in vivo, in situ, and microscale investigation of small biological organisms and cells using biocompatible surface-coated probe nanoelectrospray ionization mass spectrometry (BSCP-nanoESI-MS). A novel biocompatible surface-coated solid-phase microextration (SPME) probe is prepared, which possesses a probe-end diameter of less than 5 µm and shows excellent enrichment capacity toward lipid species. In vivo extraction of living biological organisms (e.g., zebrafishes), in situ sampling a precise position of small organisms (e.g., Daphnia magna), and even microscale analysis of single eukaryotic cells (e.g., HepG2) are easily achieved by the SPME probe. After extraction, the loaded SPME probe is directly applied for nanoESI-MS analysis, and a high-resolution mass spectrometer is employed for recording spectra and identifying lipid species. Compared with the conventional direct infusion shotgun MS lipidomics, our proposed methodology shows a similar result of lipid profiles but with simpler sample pretreatment, less sample consumption, and shorter analytical times. Lipidomics of zebrafish, Daphnia magna, and HepG2 cell populations were investigated by our proposed BSCP-nanoESI-MS methodology, and abundant lipid compositions were detected and identified and biomarkers were obtained via multivariate statistical analysis.


Assuntos
Materiais Revestidos Biocompatíveis/química , Lipídeos/análise , Animais , Daphnia , Células Hep G2 , Humanos , Espectrometria de Massas , Análise Multivariada , Propriedades de Superfície , Peixe-Zebra
19.
Anal Chim Acta ; 1022: 131-137, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-29729733

RESUMO

In this study, a system was established for the detection of tetracyclines (TCs) by simply mixing graphene quantum dots (GQDs) and Eu3+. The GQDs-Eu3+ system exhibits both strong emission of GQDs and weak characteristic emission of Eu3+ upon 360 nm excitation. In the presence of TCs, the luminescence of GQDs was quenched, while the luminescence of Eu3+ was significantly enhanced. It is worth to mention that the GQDs we prepared possess a lot of carboxyl groups on the surface and edge. This carboxyl groups play an important role in fluorescent enhancement of Eu3+. On the basis of this effect, a novel label free ratiometric sensor was developed for the detection of TCs. Under the optimized conditions, linear concentration ranges from 0 to 20 µM for tetracycline was found, and the detection limits was 8.2 nM. This system also exhibited excellent selectivity toward TCs over other antibiotics. In addition, it was successfully applied to the determination of tetracycline in river water and milk samples. The proposed system was simple in design, fast in operation, rapid in response and cost-effective. In view of the advantages, the developed system demonstrates great potential for the detection of TCs in environmental and biological samples.


Assuntos
Európio/química , Grafite/química , Limite de Detecção , Pontos Quânticos/química , Tetraciclinas/análise , Animais , Medições Luminescentes , Leite/química , Modelos Moleculares , Conformação Molecular , Rios/química , Tetraciclinas/química
20.
Am J Clin Nutr ; 107(4): 647-651, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29635504

RESUMO

Background: NuVal, developed by NuVal, LLC, is a shelf nutrition label that rates the nutritional quality of foods on a scale of 1 (worst) to 100 (best). Objective: The objective of this study was to explore the impact of the NuVal labels on food-purchasing patterns. Design: In 2014, NuVal updated its nutrient profiling system, which changed the NuVal score on many foods. We took advantage of this "natural experiment" to assess the extent to which a change in the NuVal score influenced purchases of yogurts, a category with a wide range of more and less healthy alternatives. We supplemented these data with a survey of consumers in stores using NuVal labels to obtain their experience with the labels and the extent to which they state that the labels influence their purchases. Results: Results suggested that a 1-point increase in the NuVal score is associated with a 0.49% increase in sales. Because only 8% of survey respondents reported using NuVal to influence dairy purchases, the impact of a change in the score among users may be >10 times the average effect. Conclusion: Results suggest that front-of-package nutrition labels are likely to influence purchasing patterns. This trial was registered at www.clinicaltrials.gov as NCT03390075.


Assuntos
Comportamento de Escolha , Comportamento do Consumidor , Rotulagem de Alimentos , Promoção da Saúde , Valor Nutritivo , Comércio , Alimentos/economia , Humanos , Inquéritos e Questionários , Iogurte/economia
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