Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 247
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Anal Chem ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32011124

RESUMO

Dental pulp stem cells (DPSCs) are considered one of the key cells in tooth regeneration engineering. Understanding molecular biological information on DPSCs during differentiation is of great significance for the construction of tissue-engineered teeth. In this study, we investigated the differentiation process of DPSCs stimulated by drugs and gained molecular insights in the process. By using label-free and noninvasive surface enhanced Raman spectroscopy (SERS) to monitor molecular change profiling in the cell nucleus of single DPSCs during the differentiation process, we found that two pivotal differentiation biomarkers, alkaline phosphatase (ALP) and dentin sialophosphoprotein (DSPP), were overexpressed during the process. Continuous and intermittent monitoring of SERS spectra from the nuclear region indicated that the expression of proteins and related amino acids of tryptophan were markedly increased until peak period of differentiation (on day 14). Meanwhile corresponding transformation of DNA/RNA backbone vibrational modes was also observed during the differentiation process, indicating the occurrence of replication or transcription of DNA. The method provides a useful tool for the molecular biology studies of DPSCs differentiation, and the finding will broaden our understanding of DPSCs differentiation.

2.
Sensors (Basel) ; 20(2)2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31963950

RESUMO

Nonuniformly-rotating ship refocusing is very significant in the marine surveillance of satellite synthetic aperture radar (SAR). The majority of ship imaging algorithms is based on the inverse SAR (ISAR) technique. On the basis of the ISAR technique, several parameter estimation algorithms were proposed for nonuniformly rotating ships. But these algorithms still have problems on cross-terms and noise suppression. In this paper, a refocusing algorithm for nonuniformly rotating ships based on the bilinear extended fractional Fourier transform (BEFRFT) is proposed. The ship signal in a range bin can be modeled as a multicomponent cubic phase signal (CPS) after motion compensation. BEFRFT is a bilinear extension of fractional Fourier transform (FRFT), which can estimate the chirp rates and quadratic chirp rates of CPSs. Furthermore, BEFRFT has excellent performances on cross-terms and noise suppression. The results of simulated data and Gaofen-3 data verify the effectiveness of BEFRFT.

3.
Cell Biochem Funct ; 2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31930546

RESUMO

Chemotherapy resistance has become a hold back and major clinical challenge in osteosarcoma cancer. The alteration and subcellular distribution of apurinic/apyrimidinic endonuclease 1 (APE1) has been reported to be involved in chemotherapy resistance in many cancers. Here, we report that the cytoplasmic distribution of APE1 plays a key role in the sensitivity of combination platinum chemotherapy in osteosarcoma. Interestingly, the prevalence of cisplatin-induced DNA damage and apoptosis in low cytoplasmic APE1 osteosarcoma cell lines was higher than in high expression of cytoplasmic APE1 cell lines. Overexpression of cytoplasmic APE1 protected the osteosarcoma cells from CDDP-induced apoptosis. In addition, clinical data also show that the level of cytoplasmic APE1 was negatively associated with sensitivity to combination chemotherapy of cisplatin in osteosarcoma patients. Our findings suggest that cytoplasmic APE1 plays a significant role in chemotherapy resistance. This role is a supplement to the extranuclear function of APE1, and cytoplasmic APE1 expression level could be a promising predictor of platinum treatment prognosis for osteosarcoma patients.

4.
J Cell Mol Med ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31989795

RESUMO

Sodium tanshinone IIA sulfonate (STS) has been reported to prevent Alzheimer's disease (AD). However, the mechanism is still unknown. In this study, two in vitro models, Aß-treated SH-SY5Y cells and SH-SY5Y human neuroblastoma cells transfected with APPsw (SH-SY5Y-APPsw cells), were employed to investigate the neuroprotective of STS. The results revealed that pretreatment with STS (1, 10 and 100 µmol/L) for 24 hours could protect against Aß (10 µmol/L)-induced cell toxicity in a dose-dependent manner in the SH-SY5Y cells. Sodium tanshinone IIA sulfonate decreased the concentrations of reactive oxygen species, malondialdehyde, NO and iNOS, while increased the activities of superoxide dismutase and glutathione peroxidase in the SH-SY5Y cells. Sodium tanshinone IIA sulfonate decreased the levels of inflammatory factors (IL-1ß, IL-6 and TNF-α) in the SH-SY5Y cells. In addition, Western blot results revealed that the expressions of neprilysin and insulin-degrading enzyme were up-regulated in the SH-SY5Y cells after STS treatment. Furthermore, ELISA and Western blot results showed that STS could decrease the levels of Aß. ELISA and qPCR results indicated that STS could increase α-secretase (ADAM10) activity and decrease ß-secretase (BACE1) activity. In conclusion, STS could protect against Aß-induced cell damage by modulating Aß degration and generation. Sodium tanshinone IIA sulfonate could be a promising candidate for AD treatment.

5.
J Cell Mol Med ; 24(1): 1141-1145, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31749282

RESUMO

The identification of lymph node metastases is important for the diagnosis, treatment and prognosis of patients with lung cancer. We found DDX49 was associated with the lymph node metastases in lung cancer by the Akt/ß-catenin pathway. Transcriptome sequencing, bioinformatics analysis, quantitative RT-PCR, cell transfection and the Cancer Genome Atlas (TCGA) data set were used to identify DDX49 responsible for lymph node metastases. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to explore the possible molecular mechanism in experimental cell. The DDX49 gene was correlated significantly with lymph node metastases of lung cancer. The knockdown of DDX49 inhibited the cell proliferation and migration in PC-9 and H460 cells. The mechanism research found downexpression of DDX49 decreased the Akt/ß-catenin pathway in lung cancer cell. In vivo experiments showed that DDX49 promoted the proliferation and metastases of lung cancer cells by increasing the Akt/ß-catenin pathway. These findings suggested that DDX49 may be useful as a novel biomarker of lymph node metastases and therapeutic target for lung cancer metastasis.

6.
J Chromatogr A ; 1609: 460436, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31409489

RESUMO

It is challenging to achieve absolute quantitation and accurate identification with mass spectrometry imaging (MSI) techniques. The issues facing these techniques include the uncertainty of sampling and ionization efficiencies in a localized environment, the difficulty in defining the concentration of spiked standard on tissue, and the low identification capability of MS in distinguishing isobaric compounds. In this study, we coupled continuous flow liquid microjunction surface sampling (LMJSS) with ultrahigh-performance liquid chromatography (UPLC)-MS for quantitative MSI of brain tissue. LC separation could increase the dimensions of identification and reduce the matrix effects in the tissue. A new LMJSS extraction solvent was developed to achieve exhaustive surface sampling; therefore, direct internal standard addition in the extraction solvent could be used for spot-to-spot absolute quantitation. The results showed that sphingolipids were successfully separated from their isobaric counterparts with LC-MS, and 10 sphingolipids were identified and imaged in brain tissue. The matrix effects in different locations of brain tissue with the new solvent were all in the range of 80%-150%. Compared with the traditional LMJSS solvent (90% methanol-water), the new solvent (10% 1,1,1,3,3,3-Hexafluoro-2-propanol-10% isopropanol-80% methanol) led to higher detection coverage (more lipid features) and 6-10-fold higher sensitivity for 6 identified metabolites in brain tissue. Moreover, extraction efficiencies of 80-98% for targeted sphingolipids in brain tissue were obtained with the new solvent, which allowed direct standard addition in extracts for absolute quantitation. Finally, the absolute quantitation results with LMJSS-LC-MSI were compared with those using traditional bulk tissue extraction-LC-MS, and similar quantitation results with these two methods (relative recoveries=64-119%) were obtained for sphingolipids. The absolute quantitative spatial distributions of targeted metabolites largely matched previously reported results. The method was applied to a study on the quantitative spatial changes of sphingolipids and creatine in brain after traumatic brain injury (TBI). The biological replicate results showed that 2 metabolites had significant changes after TBI in several specific regions of brain tissue.

7.
Analyst ; 145(4): 1427-1432, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31850403

RESUMO

Mitophagy, the process in which cells degrade dysfunctional organelles and recycle their nutrient substances by lysosomes, plays a vital role in cell metabolism and physiology. Herein, we present a highly targeting and near-infrared (NIR) mitochondrion fluorescent probe, which can monitor the process of autophagy. The response mechanism of the probe is based on intramolecular charge transfer (ICT) for the detection of autophagy and real-time imaging of living cells. We designed a primary amine as a pH sensitizing group, and due to the ICT process, the probe exhibits green fluorescence, and when it is protonated the ICT process is broken, and the NIR fluorescence will be restored. Simultaneously, the green fluorescence of the probe disappears. This probe exhibits excellent selectivity, high sensitivity and clean responsiveness, which indicate that it can be applied for high-targeting and high-sensitive imaging of the process of autophagy in living systems.

8.
J Pharm Biomed Anal ; 177: 112888, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31563758

RESUMO

Metabolomics measurements of seminal plasma are widely used in diagnosis and finding of molecular mechanisms of male infertility. However, so far the limitation of metabolome coverage of analytical methods hinders comprehensive metabolite biomarker finding. Moreover, the widely used case-control comparison is not enough to unveil the detailed correlations of the metabolic changes with different sperm abnormalities. In this work, we aimed to have comprehensive metabolic profiling of seminal plasma to find the metabolomics difference between healthy controls and infertility case samples with different semen abnormities by liquid chromatography-mass spectrometry (LC-MS) detection with previously established new sample preparation procedure. Among 624 detected metabolite features, 63 potential biomarkers in various metabolite classes were found for infertility in seminal plasma by multivariate analysis. Interestingly, different infertility forms have different potential biomarkers with few in common, and most of potential biomarkers were found in oligo-astheno-teratospermia samples. To further find the association of the metabolomic changes with specific sperm abnormality, sperm parameters including sperm concentration, sperm deformity rate and sperm motility were also collected, and multivariate linear regression was used to find correlations between sperm parameters and potential biomarkers. Finally, levels of 17 metabolites were found to be significantly correlated with sperm parameters. Most of correlations agreed with previously reported mechanisms of infertility, such as correlation of acylcarnitines with sperm concentration and sperm deformity, and correlation of some antioxidants with sperm deformity rate and sperm motility. Some correlations were reported for the first time, such as negative correlations of isopentenyl pyrophosphate, 2-phosphoglyceric acid and γ-glutamyl-Se-methylselenocysteine with sperm deformity rate, and negative correlation of creatine riboside with sperm concentration. All the potential biomarkers were involved in 14 metabolic pathways playing important role in energy production, antioxidation, hormone regulation and sperm membrane. These results proved previously reported molecular mechanism (such as oxidative stress and energy production) and also gave new possible clues to the pathology of male infertility, which will benefit future etiology, diagnosis and treatment of male infertility.

9.
Front Biosci (Landmark Ed) ; 25: 536-548, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585902

RESUMO

Hyperhomocysteinemia induces stress response in endoplasmic reticulum (ERS). Here, we tested whether blockage of homocysteine (Hcy) induced ERS and subsequent apoptosis in vascular smooth muscle cells can be inhibited by  blockage of PERK/eIF2α/ATF4/CHOP signaling. Short-term exposure of vascular smooth muscle cells to Hcy led to the phosphorylation of PERK (pPERK), which in turn, phosphorylated eIF2 alpha (peIF2a) and inhibited the unfolded protein response. Long-term Hcy exposure, however, increased the expression of ATF-4 and CHOP and led to apoptosis. Treatment of cells with salubrinal, a specific inhibitor for eIF2a decreased the expression of ATF-4 and CHOP, and prevented apoptosis. Together, the results show that PERK pathway is involved in Hcy-induced vascular smooth muscle cell apoptosis and that blocking the PERK pathway protects against this injury.

10.
J Med Chem ; 62(24): 11080-11107, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31789032

RESUMO

The bromodomain and extra-terminal domain (BET) family of proteins are readers which specifically recognize histone-acetylated lysine residues. Each BET bromodomain protein contains two highly homologous domains: the first bromodomain (BD1) and the second bromodomain (BD2). Pan-BET bromodomain inhibition is a potential therapy for various cancers and immune-inflammatory diseases, but only few reported inhibitors show selectivity within the BET family. Herein, we identified a series of benzo[cd]indol-2(1H)-ones and pyrrolo[4,3,2-de]quinolin-2(1H)-ones with good selectivity for BET BD1. Through structure-based optimization, highly active and selective compounds are ultimately obtained. The representative compounds are the first reported inhibitors with selectivity more than 100-fold for BRD4(1) over BRD4(2). Among them, we further show that 68 (LT052) mediates BRD4/NF-κB/NLRP3 signaling inflammatory pathways with comparable protein expression and significantly improves symptoms of gout arthritis in a rat model. Therefore, selective pharmacological modulation of individual bromodomains could represent a strategy for the treatment of acute gouty arthritis.

11.
J Phys Chem Lett ; 10(24): 7811-7816, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31804831

RESUMO

The application of optical microscopy in four-dimensional (spatial and temporal) super-resolution imaging poses challenges because of the requirement of a long acquisition time or high illumination intensity. In this paper, we introduce simultaneous two-angle axial ratiometry (STARII) for <20 nm axial super-resolution imaging and for fast and long-term imaging of live cells up to hundreds of frames per second. This method involves recording two raw images in two incident angle channels in the context of evanescent wave illumination and obtaining the corresponding intensity ratio. Furthermore, we demonstrate the combination of STARII with the lateral super-resolution method to resolve three-dimensional nanoscale structures of microtubules and to visualize the long-term dynamical plasma membrane curvature and fast remodeling of endoplasmic reticulum tubule meshwork and three-way junctions. These demonstrations indicate an important potential application of STARII in investigating nanoscale cellular complex processes in the native state.

12.
Medicine (Baltimore) ; 98(51): e18463, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861023

RESUMO

There is a lack of population-based surveys on oral health in Jilin province. Accordingly, this study aimed to understand the oral health status of 12-year-old children in Jilin province, China, to demonstrate the prevalence of oral health-related diseases, as well as to identify the associated risk factors.From February to April 2017, a cross-sectional investigation was conducted among 2324 children aged 12 years from 63 public schools of 9 regions in Jilin province, China. A questionnaire of World Health Organization (WHO) was conducted to ascertain the potential risk factors associated with oral diseases. The 3 examiners, who received theoretical and clinical training before the investigation, underwent clinical examinations to assess dental caries, dental fluorosis, presence of calculus, and gingival bleeding. Furthermore, the mean decayed-missing-filled tooth (DMFT), the rate of pit and fissure closure, education level of patients, brushing habits, and sugar consumption were also evaluated. All data analyses were conducted using SPSS version 19.0.A total of 2324 twelve-year-old children from 9 regions in Jilin-China were examined from February to April 2017. The prevalence of dental caries, dental fluorosis, calculus, and gingival bleeding reached 40.8%%, 21.8%, 47.93%, and 48.88%, respectively; the mean DMFT was 0.8787. The proportion of DMFT was 83.7% for decayed teeth, 0.2% for missing teeth, and 16.1% for filling teeth. The prevalence of pit and fissure closure was 10%.Educational level of parents was negatively correlated with the prevalence of oral diseases, whereas sugar consumption was positively associated with dental caries prevalent in children. We also found that there was no association between brushing habits and dental caries in children aged 12 years in Jilin Province.


Assuntos
Índice CPO , Cárie Dentária/epidemiologia , Fluorose Dentária/epidemiologia , Saúde Bucal/estatística & dados numéricos , Criança , China/epidemiologia , Açúcares da Dieta , Conhecimentos, Atitudes e Prática em Saúde , Humanos
13.
Appl Opt ; 58(33): 9069-9074, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31873583

RESUMO

In this paper, a new method is proposed for super-resolution imaging of non-fluorescent samples. This approach is based on the intensity difference between confocal image and negative confocal image, which are simultaneously acquired at one sample scanning. In order to get these two different images simultaneously, the sample was illuminated by two different focused spots from the same laser source: the doughnut spot and the solid spot. The effectiveness of the label-free difference microscopy based on parallel detection was validated by experiments on some samples including 80 nm gold beads, 100 nm silver nanowires, and Blu-ray DVD without fluorescent dyes. By subtraction of the reflected light intensity from the sample, the final resolution of the image without deconvolution was enhanced about 1.6 times compared with confocal imaging. This technique can be applied to surface topography detection of metallographic or other non-fluorescent materials.

14.
Opt Express ; 27(26): 38337-38348, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31878602

RESUMO

For a long term, spatial resolution of fluorescence microscopy was strictly restricted by the diffraction limit. To solve this problem, various super-resolution technologies have been developed. Super-resolution radial fluctuations (SRRF), an emerging type of super-resolution microscopy, directly analyze raw images and generate super-resolution results without fluorophore localization, thereby showing more advantages in handling high-density data. Here, by speeding up the process of the algorithm with graphics processing unit (GPU) and programming with Python language, we expand the universality and improve the computing speed of the SRRF algorithm. We further apply our SRRF algorithm in different live-cell super-resolution microscopy methods with two types of fluorescence fluctuation sources: (i) direct stochastic optical reconstruction microscopy (dSTORM) in which fluorophores themselves blink under specific buffer and laser condition and (ii) structural illumination microscopy (SIM) and modulated Airyscan in which fluorescence fluctuations are artificially introduced with modulated laser illumination. With improved spatiotemporal resolution and image quality, our SRRF algorithm demonstrates its capability in live-cell super-resolution imaging, indicating its wide applications in life sciences.

15.
Front Microbiol ; 10: 2576, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781072

RESUMO

Fish are the most widespread aquaculture species and maintain complex associations with microbial consortiums. However, the ecology of these associations present in multiple microhabitats in fish remains elusive, especially on the microbial assembly in fish external (skin and gill) and internal (stomach and intestine) niches, and the relationship with the rearing environment. To understand host dependence and niche differentiation of organ-specific microbiome signatures using a 16S rRNA gene-based sequencing technique, we systematically provided characterizations of a comparative framework relevant to the microbiome of stomach, regional intestine, skin, and gill in two important farmed fish species, herbivorous grass carp (Ctenopharyngodon idella) and carnivorous southern catfish (Silurus meridionalis), and of the rearing water. The different feeding habits of grass carp and southern catfish showed a significant separation of microbial community structure, with great compositional differences across body sites within each species. Site-driven divergences relied on host species: the same types of microhabitats between grass carp and southern catfish harbored differential microbiome. Additionally, body sites had remarkably distinct communities and displayed lower alpha diversity compared to rearing water. Unexpectedly, the stomach of southern catfish had the highest microbial diversity in the digestive tract of the two co-cultured fish species. For external sites within each species, a higher diversity occurred in gill of grass carp and in skin of southern catfish. Our results unveil different topographical microbiome signatures of the co-cultured species, indicating host selection in individual-level microbial assemblages and niche differentiation at the organ scale. This work represents a foundation for understanding the comprehensive microbial ecology of cohabiting farmed fish, suggesting potential applications associated with fish microbiome that urgently needs to be assessed in polycultured operations in aquaculture.

16.
J Med Chem ; 62(23): 10605-10616, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31751136

RESUMO

Activation of the leukotriene A4 hydrolase (LTA4H) aminopeptidase (AP) activity with 4-methoxydiphenylmethane (4MDM) promoted resolution of neutrophil infiltration in a murine cigarette smoke-induced model for emphysematous chronic obstructive pulmonary disease. Recently, 4-(4-benzylphenyl)thiazol-2-amine (ARM1) was published as a ligand for LTA4H with potential anti-inflammatory properties. To investigate the effect of modifier structure on enzyme kinetics of LTA4H, a series of analogues bearing structural features of ARM1 and 4MDM were synthesized using trifluoroborate Suzuki coupling reactions. Following, the 2.8 Å X-ray crystal structure of LTA4H complexed with 4-OMe-ARM1, a 4MDM-ARM1 hybrid molecule, was determined. Kinetic analysis showed that ARM1 and related analogues lowered affinity for the enzyme-substrate complex, resulting in a change of mechanism from hyperbolic mixed predominately catalytic activation (HMx(Sp < Ca)A) as observed for 4MDM to a predominately specific activation (HMx(Sp > Ca)A) mechanism. 4-OMe-ARM1 was then shown to dose responsively reduce LTB4 production in human neutrophils.

17.
Adv Appl Microbiol ; 109: 31-59, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31677646

RESUMO

Basic helix-loop-helix (bHLH) proteins belong to a superfamily of transcription factors, and they are widely distributed in eukaryotic organisms. Members of the bHLH protein family can form homodimers or heterodimers with themselves or other family members, and they often play bifunctional roles as activators and repressors to uniquely regulate the transcription of downstream target genes. The bHLH transcription factors are usually involved in developmental processes, including cellular proliferation and differentiation. Therefore, these transcription factors often play crucial roles in regulating growth, development, and differentiation in eukaryotes. Aspergillus species fungi are widely distributed in the environment, and they play important roles not only in the decomposition of organic matter as an important environmental microorganism but also in the fermentation and the food processing industry. Furthermore, some pathogenic fungi, such as Aspergillus flavus and Aspergillus fumigatus, affect the environment and human health in important ways. Recent research has shown that some Aspergillus bHLH proteins are significantly involved in the regulation of asexual and sexual reproduction, secondary metabolite production, carbohydrate metabolism, conidial and sclerotial production, among other processes. Here, we review the regulatory mechanisms and biological functions of the bHLH transcription factors of the Aspergillus genus to provide a theoretical reference for further study on the growth and development of Aspergillus and the functions of bHLHs.

18.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(5): 521-526, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31721501

RESUMO

The malignant tumors including oral cancer, colorectal cancer, pancreatic cancer, and esophageal cancer, of the digestive system are a common high-fatal malignancy. Porphyromonas gingivalis, as the most important pathogen of periodontal disease, has been gradually proved that its invasiveness occurs not only in the mouth but also in other parts of the digestive system. Moreover, the relevant pathogenic mechanism is increasingly attracting the reseachers' attention. In this study, the role and possible pathogenesis of Porphyromonas gingivalis in the digestive system are described in a systematic and comprehensive way.


Assuntos
Neoplasias Bucais , Doenças Periodontais , Humanos , Porphyromonas gingivalis
19.
J Microsc ; 276(2): 98-106, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31691969

RESUMO

Here, we propose a novel imaging method, which is called image scanning difference microscopy (ISDM), for superresolution imaging. In ISDM, we implement a detector array composed of 19 avalanche photodiodes (APD) rather than single-point detector in standard confocal microscopy for reconstructing superresolved images with higher signal-to-noise ratio (SNR). Combining with our former proposed fluorescence emission difference (FED) method, we have achieved a lateral resolution of 111 nm (∼λ/6) without the damage of image quality, the highest FED resolution to the best of our knowledge. With its simple setup and remarkable performance, we believe that ISDM can become a versatile observation tool in biology and other fundamental studies. LAY DESCRIPTION: Fluorescence emission difference (FED) microscopy is a really simple and generalisable superresolved fluorescence microscopy method based on PSF engineering and difference algorithm recently. Compared to stimulated-emission-depletion fluorescence microscopy (STED), FED don't need complicated system or precise alignment and polarisation, available for wide variety of dyes and has low photobleaching and phototoxicity for living cells. However, the distortion caused by negative value is one of the biggest obstacles to the further development of FED. In light of this, we propose a novel superresolution imaging method based on the FED method with parallel detection system, which is called image scanning difference microscopy (ISDM). Our method has achieved a significant breakthrough in FED, increasing the resolution further while reducing artefacts generated by negative values, which cannot be accomplished through combining other methods. In addition, ISDM does not require complex setup and optical alignment, long time imaging and imposing no constraint on dyes. Importantly, we realised a transverse resolution of ∼λ/6 (triple diffraction limit) with single wavelength, single incident path and low light intensity, which has never been achieved in any other far-field superresolution microscopy.

20.
ACS Chem Biol ; 14(12): 2546-2552, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31742988

RESUMO

Affinity-based protein profiling has proven to be a powerful method in target identification of bioactive molecules. Here, this technology was applied in two photoreactive anticancer inhibitors, arenobufagin and HM30181. Using UV irradiation, these photoreactive reagents can covalently cross-link to target proteins, leading to a covalent binding with target proteins. Moreover, the cellular on/off targets of these two molecules, including ATP1A1, MDR1, PARP1, DDX5, NOP2, RAB6A, and ERGIC1 were first identified by affinity-based protein profiling and bioimaging approaches. The protein hit, PARP1, was further validated to be involved in the function of the anticancer effects.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA