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1.
BMC Genomics ; 25(1): 242, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443802

RESUMO

BACKGROUND: 5-Methylcytosine (5mC) plays a very important role in gene stability, transcription, and development. Therefore, accurate identification of the 5mC site is of key importance in genetic and pathological studies. However, traditional experimental methods for identifying 5mC sites are time-consuming and costly, so there is an urgent need to develop computational methods to automatically detect and identify these 5mC sites. RESULTS: Deep learning methods have shown great potential in the field of 5mC sites, so we developed a deep learning combinatorial model called i5mC-DCGA. The model innovatively uses the Convolutional Block Attention Module (CBAM) to improve the Dense Convolutional Network (DenseNet), which is improved to extract advanced local feature information. Subsequently, we combined a Bidirectional Gated Recurrent Unit (BiGRU) and a Self-Attention mechanism to extract global feature information. Our model can learn feature representations of abstract and complex from simple sequence coding, while having the ability to solve the sample imbalance problem in benchmark datasets. The experimental results show that the i5mC-DCGA model achieves 97.02%, 96.52%, 96.58% and 85.58% in sensitivity (Sn), specificity (Sp), accuracy (Acc) and matthews correlation coefficient (MCC), respectively. CONCLUSIONS: The i5mC-DCGA model outperforms other existing prediction tools in predicting 5mC sites, and it is currently the most representative promoter 5mC site prediction tool. The benchmark dataset and source code for the i5mC-DCGA model can be found in https://github.com/leirufeng/i5mC-DCGA .


Assuntos
5-Metilcitosina , Benchmarking , Regiões Promotoras Genéticas , Projetos de Pesquisa , Software
2.
Angew Chem Int Ed Engl ; 63(27): e202401448, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38530747

RESUMO

Photogenerated radicals are an indispensable member of the state-of-the-art photochromic material family, as they can effectively modulate the photoluminescence and photothermal conversion performance of radical-induced photochromic complexes. Herein, two novel radical-induced photochromic metal-organic frameworks (MOFs), [Ag(TEPE)](AC) ⋅ 7/4H2O ⋅ 5/4EtOH (1) and [Ag(TEPE)](NC) ⋅ 3H2O ⋅ EtOH (2), are reported. Distinctly different topological networks can be obtained by judiciously introducing alternative π-conjugated anionic guests, including a new topological structure (named as sfm) first reported in this work, describing as 4,4,4,4-c net. EPR data and UV-Vis spectra prove the radical-induced photochromic mechanism. Dynamic photochromism exhibits tunability in a wide CIE color space, with a linear segment from yellow to red for 1, while a curved coordinate line for 2, resulting in colorful emission from blue to orange. Moreover, photogenerated TEPE* radicals effectively activate the near-infrared (NIR) photothermal conversion effect of MOFs. Under 1 W cm-2 808 nm laser irradiation, the surface temperatures of photoproducts 1* and 2* can reach ~160 °C and ~120 °C, respectively, with competitive NIR photothermal conversion efficiencies η=51.8 % (1*) and 36.2 % (2*). This work develops a feasible electrostatic compensation strategy to accurately introduce photoactive anionic guests into MOFs to construct multifunctional radical-induced photothermal conversion materials with tunable photoluminescence behavior.

3.
BMC Bioinformatics ; 24(1): 397, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880673

RESUMO

BACKGROUND: N6, 2'-O-dimethyladenosine (m6Am) is an abundant RNA methylation modification on vertebrate mRNAs and is present in the transcription initiation region of mRNAs. It has recently been experimentally shown to be associated with several human disorders, including obesity genes, and stomach cancer, among others. As a result, N6,2'-O-dimethyladenosine (m6Am) site will play a crucial part in the regulation of RNA if it can be correctly identified. RESULTS: This study proposes a novel deep learning-based m6Am prediction model, EMDL_m6Am, which employs one-hot encoding to expressthe feature map of the RNA sequence and recognizes m6Am sites by integrating different CNN models via stacking. Including DenseNet, Inflated Convolutional Network (DCNN) and Deep Multiscale Residual Network (MSRN), the sensitivity (Sn), specificity (Sp), accuracy (ACC), Mathews correlation coefficient (MCC) and area under the curve (AUC) of our model on the training data set reach 86.62%, 88.94%, 87.78%, 0.7590 and 0.8778, respectively, and the prediction results on the independent test set are as high as 82.25%, 79.72%, 80.98%, 0.6199, and 0.8211. CONCLUSIONS: In conclusion, the experimental results demonstrated that EMDL_m6Am greatly improved the predictive performance of the m6Am sites and could provide a valuable reference for the next part of the study. The source code and experimental data are available at: https://github.com/13133989982/EMDL-m6Am .


Assuntos
Aprendizado Profundo , Humanos , RNA Mensageiro/genética , RNA , Metilação , Software
4.
Analyst ; 148(14): 3359-3370, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37365912

RESUMO

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged as a novel pathogen in 2019. The virus is responsible for a severe acute respiratory syndrome outbreak, affecting the respiratory system of infected individuals. COVID-19 is a super amplifier of basic diseases, and the disease with basic diseases is often more serious. Controlling the spread of the COVID-19 pandemic relies heavily on the timely and accurate detection of the virus. To resolve the problem, a polyaniline functionalized NiFeP nanosheet array-based electrochemical immunosensor using Au/Cu2O nanocubes as a signal amplifier is fabricated for the detection of SARS-CoV-2 nucleocapsid protein (SARS-CoV-2 NP). Polyaniline (PANI) functionalized NiFeP nanosheet arrays are synthesized as an ideal sensing platform for the first time. PANI is coated on the surface of NiFeP by electropolymerization to enhance biocompatibility, beneficial for the efficient loading of the capture antibody (Ab1). Significantly, Au/Cu2O nanocubes possess excellent peroxidase-like activity and exhibit outstanding catalytic activity for the reduction of H2O2. Therefore, Au/Cu2O nanocubes combine with a labeled antibody (Ab2) through the Au-N bond to form labeled probes, which can effectively amplify current signals. Under optimal conditions, the immunosensor for the detection of SARS-CoV-2 NP shows a wide linear range of 10 fg mL-1-20 ng mL-1 and a low detection limit of 1.12 fg mL-1 (S/N = 3). It also exhibits desirable selectivity, repeatability, and stability. Meanwhile, the excellent analytical performance in human serum samples confirms the practicality of the PANI functionalized NiFeP nanosheet array-based immunosensor. The electrochemical immunosensor based on the Au/Cu2O nanocubes as a signal amplifier demonstrates great potential for application in the personalized point-of-care (POC) clinical diagnosis.


Assuntos
Técnicas Biossensoriais , COVID-19 , Nanopartículas Metálicas , Humanos , SARS-CoV-2 , Peróxido de Hidrogênio/química , Pandemias , Anticorpos Imobilizados , Imunoensaio , COVID-19/diagnóstico , Anticorpos , Proteínas do Nucleocapsídeo , Técnicas Eletroquímicas , Ouro/química , Limite de Detecção , Nanopartículas Metálicas/química
5.
Bioorg Med Chem Lett ; 88: 129263, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37004924

RESUMO

Glycogen synthase kinase-3ß (GSK-3ß) regulates numerous of CNS-specific signaling pathways, and is particularly implicated in various pathogenetic mechanisms of Alzheimer's disease (AD). A noninvasive method for detecting GSK-3ß in AD brains via positron emission tomography (PET) imaging could enhance the understanding of AD pathogenesis and aid in the development of AD therapeutic drugs. In this study, an array of fluorinated thiazolyl acylaminopyridines (FTAAP) targeting GSK-3ß were designed and synthesized. These compounds showed moderate to high affinities (IC50 = 6.0 - 426 nM) for GSK-3ß in vitro. A potential GSK-3ß tracer, [18F]8, was successfully radiolabeled. [18F]8 had unsatisfactory initial brain uptake despite its suitable lipophilicity, molecular size and good stability. Further structural refinement of the lead compound is needed to develop promising [18F]-labeled radiotracers for the detection of GSK-3ß in AD brains.


Assuntos
Doença de Alzheimer , Encéfalo , Humanos , Glicogênio Sintase Quinase 3 beta/metabolismo , Ligantes , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Fosforilação
6.
Bioorg Med Chem Lett ; 80: 129112, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36565966

RESUMO

Cytochrome P450 1B1 (CYP1B1) is highly expressed in a variety of tumors and implicated to drug resistance. More and more researches have suggested that CYP1B1 is a new target for cancer prevention and therapy. Various CYP1B1 inhibitors with a rigid polycyclic skeleton have been developed, such as flavonoids, trans-stilbenes, and quinazolines. To obtain a new class of CYP1B1 inhibitors, we designed and synthesized a series of bentranil analogues, moreover, IC50 determinations were performed for CYP1B1 inhibition of five of these compounds and found that 6o and 6q were the best inhibitors, with IC50 values in the nM range. The selectivity index (SI) of CYP1B1 over CYP1A1 and CYP1A2 was 30-fold higher than that of α-naphthoflavone (ANF). The molecular docking results showed that compound 6q fitted better into the CYP1B1 binding site than other compounds, which was consistent with our experimental results. On the basis of 6o and 6q, it is expected to develop CYP1B1 inhibitors with stronger affinity, higher selectivity and better solubility.


Assuntos
Citocromo P-450 CYP1A1 , Inibidores das Enzimas do Citocromo P-450 , Simulação de Acoplamento Molecular , Citocromo P-450 CYP1B1/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Sítios de Ligação
7.
Inorg Chem ; 62(3): 1075-1085, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36625763

RESUMO

Herein, hexaazamacrocyclic ligand LN6 was employed to construct a series of photochromic rare-earth complexes, [Ln(LN6)(NO3)2](BPh4) [1-Ln, Ln = Dy, Tb, Eu, Gd, Y; LN6 = (3E,5E,10E,12E)-3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane-3,5,10,12-tetraene]. The behavior of photogenerated radicals of hexaazamacrocyclic ligands was revealed for the first time. Upon 365 nm light irradiation, complexes 1-Ln exhibit photochromic behavior induced by photogenerated radicals according to EPR and UV-vis analyses. Static and dynamic magnetic studies of 1-Dy and irradiated product 1-Dy* indicate weak ferromagnetic interactions among DyIII ions and photogenerated LN6 radicals, as well as slow magnetization relaxation behavior under a 2 kOe applied field. Further fitting analyses show that the magnetization relaxation in 1-Dy* is markedly different from 1-Dy. Time-dependent fluorescence measurements reveal the characteristic luminescence quenching dynamics of lanthanide in the photochromic process. Especially for irradiated product 1-Eu*, the luminescence is almost completely quenched within 5 min with a quenching efficiency of 98.4%. The results reported here provide a prospect for the design of radical-induced photochromic lanthanide single-molecule magnets and will promote the further development of multiresponsive photomagnetic materials.


Assuntos
Elementos da Série dos Lantanídeos , Luminescência , Magnetismo , Imãs , Fluorescência , Ligantes
8.
Curr Genomics ; 24(3): 171-186, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38178985

RESUMO

Introduction: N4 acetylcytidine (ac4C) is a highly conserved nucleoside modification that is essential for the regulation of immune functions in organisms. Currently, the identification of ac4C is primarily achieved using biological methods, which can be time-consuming and labor-intensive. In contrast, accurate identification of ac4C by computational methods has become a more effective method for classification and prediction. Aim: To the best of our knowledge, although there are several computational methods for ac4C locus prediction, the performance of the models they constructed is poor, and the network structure they used is relatively simple and suffers from the disadvantage of network degradation. This study aims to improve these limitations by proposing a predictive model based on integrated deep learning to better help identify ac4C sites. Methods: In this study, we propose a new integrated deep learning prediction framework, DLC-ac4C. First, we encode RNA sequences based on three feature encoding schemes, namely C2 encoding, nucleotide chemical property (NCP) encoding, and nucleotide density (ND) encoding. Second, one-dimensional convolutional layers and densely connected convolutional networks (DenseNet) are used to learn local features, and bi-directional long short-term memory networks (Bi-LSTM) are used to learn global features. Third, a channel attention mechanism is introduced to determine the importance of sequence characteristics. Finally, a homomorphic integration strategy is used to limit the generalization error of the model, which further improves the performance of the model. Results: The DLC-ac4C model performed well in terms of sensitivity (Sn), specificity (Sp), accuracy (Acc), Mathews correlation coefficient (MCC), and area under the curve (AUC) for the independent test data with 86.23%, 79.71%, 82.97%, 66.08%, and 90.42%, respectively, which was significantly better than the prediction accuracy of the existing methods. Conclusion: Our model not only combines DenseNet and Bi-LSTM, but also uses the channel attention mechanism to better capture hidden information features from a sequence perspective, and can identify ac4C sites more effectively.

9.
BMC Bioinformatics ; 23(1): 450, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316638

RESUMO

BACKGROUND: Lysine succinylation is a newly discovered protein post-translational modifications. Predicting succinylation sites helps investigate the metabolic disease treatments. However, the biological experimental approaches are costly and inefficient, it is necessary to develop efficient computational approaches. RESULTS: In this paper, we proposed a novel predictor based on ensemble dense blocks and an attention module, called as pSuc-EDBAM, which adopted one hot encoding to derive the feature maps of protein sequences, and generated the low-level feature maps through 1-D CNN. Afterward, the ensemble dense blocks were used to capture feature information at different levels in the process of feature learning. We also introduced an attention module to evaluate the importance degrees of different features. The experimental results show that Acc reaches 74.25%, and MCC reaches 0.2927 on the testing dataset, which suggest that the pSuc-EDBAM outperforms the existing predictors. CONCLUSIONS: The experimental results of ten-fold cross-validation on the training dataset and independent test on the testing dataset showed that pSuc-EDBAM outperforms the existing succinylation site predictors and can predict potential succinylation sites effectively. The pSuc-EDBAM is feasible and obtains the credible predictive results, which may also provide valuable references for other related research. To make the convenience of the experimental scientists, a user-friendly web server has been established ( http://bioinfo.wugenqiang.top/pSuc-EDBAM/ ), by which the desired results can be easily obtained.


Assuntos
Lisina , Ácido Succínico , Lisina/metabolismo , Ácido Succínico/metabolismo , Proteínas/metabolismo , Sequência de Aminoácidos , Processamento de Proteína Pós-Traducional , Atenção , Biologia Computacional/métodos
10.
J Am Chem Soc ; 144(19): 8837-8847, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35503109

RESUMO

Here, we report the molecular self-assembly of hydroxido-bridged {Ln5Ni6} ((Ln3+ = Dy3+, Y3+) metal clusters by the reaction of enantiopure chiral ligands, namely, (R/S)-(2-hydroxy-3-methoxybenzyl)-serine), with NiII and LnIII precursors. Single-crystal diffraction analysis reveals that these compounds are isostructural sandwich-like 3d-4f heterometallic clusters showing helical chirality. Direct current magnetic measurements on {Dy5Ni6} indicates ferromagnetic coupling between DyIII and NiII centers, whereas those on {Y5Ni6} denote that the NiII centers are antiferromagnetically coupled and/or magnetically anisotropic. Magneto-chiral dichroism (MChD) measurements on {Dy5Ni6} and its comparison to that of {Y5Ni6} provide the first experimental observation of intense multimetal site MChD signals in the visible-near-infrared region. Moreover, the comparison of MChD with natural and magnetic circular dichroism spectra unambiguously demonstrate for the first time that the MChD signals associated with the NiII d-d transitions are mostly driven by natural optical activity and those associated with the DyIII f-f transitions are driven by magnetic optical activity.


Assuntos
Elementos da Série dos Lantanídeos , Compostos Organometálicos , Cristalografia por Raios X , Elementos da Série dos Lantanídeos/química , Fenômenos Magnéticos , Magnetismo , Compostos Organometálicos/química
11.
Mol Divers ; 25(1): 525-533, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32410113

RESUMO

Cerebral amyloid angiopathy (CAA) commonly found in the aged is pathologically characterized by ß-amyloid (Aß) deposition in the walls of arteries and capillaries of brain. In this study, four flexible multidentate benzyldiamine derivatives as potential probes for cerebrovascular Aß deposition were designed and synthesized. In in vitro inhibition assays, the ligands 18-21 displayed high affinities for Aß aggregates with Ki values of 1.45 ± 0.53 nM, 1.68 ± 0.35 nM, 1.16 ± 0.23 nM and 1.72 ± 0.19 nM, respectively. A significant improvement in the binding affinity over the monomer, compounds 9-12 or benzyldiamine derivatives, demonstrated the applicability of the multidentate approach. The underlying mechanism of these novel Aß agents was explored by molecular docking technique, which theoretically verified the high affinities of the multidentate benzyldiamine derivatives for Aß aggregates. Moreover, the molecular masses of the ligands 18-21 are more than 700 Dalton, which are believed to be hardly capable of penetrating blood brain barrier. In this regard, these ligands could be used to distinguish CAA from Alzheimer's disease which is another Aß-related disorder disease. To convert these ligands to positron emission tomography imaging agents, we attempted to radiosynthesize [18F]18. Though the radiolabeling was not very successful, the preliminary results suggested that these newly proposed multidentate benzyldiamine derivatives may be used as potential Aß imaging agents in cerebral amyloid angiopathy.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Benzilaminas/uso terapêutico , Angiopatia Amiloide Cerebral/tratamento farmacológico , Benzilaminas/química , Benzilaminas/farmacologia , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Simulação de Acoplamento Molecular , Agregados Proteicos
12.
Angew Chem Int Ed Engl ; 60(8): 4150-4157, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33174359

RESUMO

The organoplatinum(II) complex [Pt(C^N^N)(Cl)] (C^N^N=5,6-diphenyl-2,2'-bipyridine, Pt1) can assemble into nanoaggregates via π-π stacking and complementary hydrogen bonds, rather than Pt-Pt interactions. Pt1 exhibits ratiometric dual emission, including rare blue emission (λem =445 nm) and assembly-induced yellow emission (λem =573 nm), under one- and two-photon excitation. Pt1 displays blue emission in cells with an intact membrane due to its low cellular uptake. In cells where the membrane is disrupted, uptake of the complex is increased and at higher concentrations yellow emission is observed. The ratio of yellow to blue emission shows a linear relationship to the loss of cell membrane integrity. Pt1 is, to our knowledge, the first example of an assembly-induced two-photon ratiometric dual emission organoplatinum complex. The excellent and unique characteristics of the complex enabled its use for the tracking of cell apoptosis, necrosis, and the inflammation process in zebrafish.


Assuntos
Complexos de Coordenação/química , Microscopia de Fluorescência por Excitação Multifotônica , Platina/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/metabolismo , Complexos de Coordenação/farmacologia , Humanos , Inflamação/induzido quimicamente , Inflamação/diagnóstico por imagem , Larva/química , Larva/metabolismo , Piridinas/química , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo
13.
Plant Cell Environ ; 43(3): 732-744, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31724184

RESUMO

Silicon (Si) accumulation in shoots differs greatly with plant species, but the molecular mechanisms for this interspecific difference are unknown. Here, we isolated homologous genes of rice Si influx (SlLsi1) and efflux (SlLsi2) transporter genes in tomato (Solanum lycopersicum L.) and functionally characterized these genes. SlLsi1 showed transport activity for Si when expressed in both rice lsi1 mutant and Xenopus laevis oocytes. SlLsi1 was constitutively expressed in the roots. Immunostaining showed that SlLsi1 was localized at the plasma membrane of both root tip and basal region without polarity. Furthermore, overexpression of SlLsi1 in tomato increased Si concentration in the roots and root cell sap but did not alter the Si concentration in the shoots. By contrast, two Lsi2-like proteins did not show efflux transport activity for Si in Xenopus oocytes. However, when functional CsLsi2 from cucumber was expressed in tomato, the Si uptake was significantly increased, resulting in higher Si accumulation in the leaves and enhanced tolerance of the leaves to water deficit and high temperature. Our results suggest that the low Si accumulation in tomato is attributed to the lack of functional Si efflux transporter Lsi2 required for active Si uptake although SlLsi1 is functional.


Assuntos
Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Silício/metabolismo , Solanum lycopersicum/metabolismo , Adaptação Fisiológica , Clonagem Molecular , Desidratação , Eletrólitos/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Teste de Complementação Genética , Resposta ao Choque Térmico , Solanum lycopersicum/genética , Proteínas de Membrana Transportadoras/genética , Mutação/genética , Oryza/genética , Proteínas de Plantas/genética , Raízes de Plantas/genética , Plantas Geneticamente Modificadas , Transporte Proteico , Frações Subcelulares/metabolismo
14.
Mol Pharm ; 17(11): 4089-4100, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32845647

RESUMO

The highly rigid and planar scaffolds with π-conjugated systems have been widely considered to be indispensable for ß-amyloid (Aß) binding ligands. In this study, a library of diphenoxy compounds with different types of more flexible linkers as Aß ligands were synthesized and evaluated. Most of them displayed good affinity (Ki < 100 nM) for Aß1-42 aggregates, and some ligands even showed values of Ki less than 10 nM. Structure-activity relationship analysis revealed that modification on the linkers or substituents tolerated great flexibility, which challenged the long-held belief that rigid and planar structures are exclusively favored for Aß binding. Three ligands were labeled by iodine-125, and they exhibited good properties in vitro and in vivo, which further supported that this flexible scaffold was potential and promising for the development of Aß imaging agents.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Fenóis/química , Fenóis/metabolismo , Piperazina/química , Placa Amiloide/metabolismo , Polietilenoglicóis/química , Propano/química , Animais , Autorradiografia/métodos , Encéfalo/metabolismo , Humanos , Radioisótopos do Iodo/química , Ligantes , Camundongos , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Fenóis/síntese química , Compostos Radiofarmacêuticos/metabolismo , Relação Estrutura-Atividade , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/métodos
15.
Bioorg Med Chem Lett ; 30(11): 127160, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32247732

RESUMO

The objective of the study was to prepare and evaluate a 18F-radiolabled tracer (Al18F-5), derivated from the antitumor agent 2-(4-aminophenyl)benzothiazole, as a PET probe for tumor imaging. Al18F-5 was successfully prepared with approx. 40% radiochemical yield in aqueous phase. In in vitro cell uptake experiments and competition assay, Al18F-5 displayed good tumor-binding ability and specificity in HeLa cells (24.7 ± 0.9% ID/106 cells, IC50 = 63.8 ± 13.6 nM) and MCF-7 cells (6.8 ± 0.3% ID/106 cells, IC50 = 331.1 ± 33.7 nM). The nonradioactive compound, Al19F-5, visibly marked HeLa cells and MCF-7 cells but did not stain HEB cells in florescent staining, which further indicated the tumor-binding ability of Al18F-5. In in vivo PET imaging, HeLa and MCF-7 tumors were clearly delineated by specific accumulation of Al18F-5 in model mice. In biodistribution study, Al18F-5 exhibited good tumor uptake (4.66 ± 0.13% ID/g and 3.69 ± 0.56% ID/g, respectively), moderate tumor-to-muscle ratio (3.38 and 2.48, respectively) at 1 h post injection, which were in a good consistency with the results of PET imaging. In conclusion, Al18F-5 might be developed as a candidate PET probe for tumor imaging, though additional optimizations are still needed to improve pharmacokinetics in vivo.


Assuntos
Benzotiazóis/química , Meios de Contraste/química , Compostos Radiofarmacêuticos/síntese química , Animais , Benzotiazóis/metabolismo , Linhagem Celular Tumoral , Meios de Contraste/metabolismo , Radioisótopos de Flúor/química , Humanos , Camundongos , Microscopia de Fluorescência , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/metabolismo , Distribuição Tecidual , Transplante Heterólogo
16.
BMC Plant Biol ; 19(1): 164, 2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31029105

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are 3'-5' head-to-tail covalently closed non-coding RNA that have been proved to play essential roles in many cellular and developmental processes. However, no information relate to cucumber circRNAs is available currently, especially under salt stress condition. RESULTS: In this study, we sequenced circRNAs in cucumber and a total of 2787 were identified, with 1934 in root and 44 in leaf being differentially regulated under salt stress. Characteristics analysis of these circRNAs revealed following features: most of them are exon circRNAs (79.51%) and they prefer to arise from middle exon(s) of parent genes (2035/2516); moreover, most of circularization events (88.3%) use non-canonical-GT/AG splicing signals; last but not least, pairing-driven circularization is not the major way to generate cucumber circRNAs since very few circRNAs (18) contain sufficient flanking complementary sequences. Annotation and enrichment analysis of both parental genes and target mRNAs were launched to uncover the functions of differentially expressed circRNAs induced by salt stress. The results showed that circRNAs may be paly roles in salt stress response by mediating transcription, signal transcription, cell cycle, metabolism adaptation, and ion homeostasis related pathways. Moreover, circRNAs may function to regulate proline metabolisms through regulating associated biosynthesis and degradation genes. CONCLUSIONS: The present study identified large number of cucumber circRNAs and function annotation revealed their possible biological roles in response to salt stress. Our findings will lay a solid foundation for further structure and function studies of cucumber circRNAs.


Assuntos
Cucumis sativus/genética , Cucumis sativus/fisiologia , RNA de Plantas/genética , RNA/genética , Estresse Salino/genética , Sequência de Bases , Biomassa , Cucumis sativus/crescimento & desenvolvimento , Éxons/genética , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Redes Reguladoras de Genes , Genes de Plantas , Transporte de Íons , MicroRNAs/genética , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , RNA/metabolismo , RNA Circular , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA de Plantas/metabolismo
17.
J Theor Biol ; 460: 195-203, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30312687

RESUMO

Investigation into the network of protein-protein interactions (PPIs) will provide valuable insights into the inner workings of cells. Accordingly, it is crucially important to develop an automated method or high-throughput tool that can efficiently predict the PPIs. In this study, a new predictor, called "iPPI-PseAAC(CGR)", was developed by incorporating the information of "chaos game representation" into the PseAAC (Pseudo Amino Acid Composition). The advantage by doing so is that some key sequence-order or sequence-pattern information can be more effectively incorporated during the treatment of the protein pair samples. The operation engine used in this predictor is the random forests algorithm. It has been observed via the cross-validations on the widely used benchmark datasets that the success rates achieved by the proposed predictor are remarkably higher than those by its existing counterparts. For the convenience of the most experimental scientists, a user-friendly web-server for the new predictor has been established at http://www.jci-bioinfo.cn/iPPI-PseAAC(CGR), by which users can easily get their desired results without the need to go through the detailed mathematics.


Assuntos
Algoritmos , Biologia Computacional/métodos , Mapas de Interação de Proteínas , Sequência de Aminoácidos , Aminoácidos , Dinâmica não Linear
18.
Inorg Chem ; 58(2): 1301-1308, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30592214

RESUMO

A family of dinuclear dysprosium cores bridged by different ligands within a polyoxometalates (POMs) framework, (TBA)8.5H1.5[(PW11O39)2Dy2X2(H2O)2]·6H2O (X = OH (1), F (2), OAc (3); TBA = tetra- n-butylammonium), was successfully synthesized and structurally characterized. Magnetic studies indicate that the bridging ligands can significantly affect the magnetic behaviors, with 1 and 3 showing antiferromagnetic coupling and 2 bridged by fluoride ions showing ferromagnetic interaction. 1 and 2 behaved as single-molecule magnets (SMMs) with the thermally activated energy barrier of 98(5) and 74(6) cm-1 under zero dc filed, respectively, whereas no SMM behavior was observed for 3 bridged by two µ-η1:η2-acetato ligands. Notably, the low-temperature fluorescence spectra of 1-3 provide valuable information on the energy levels, which are consistent with the anisotropic barriers determined by magnetic measurements. These results offer an insight into the magneto-optical correlation. Furthermore, the effective energy barrier of 1 reaches a breakthrough among all POM-based SMMs.

19.
Ecotoxicol Environ Saf ; 174: 245-254, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30831473

RESUMO

Salinity decreases the yield and quality of crops. Silicon (Si) has been widely reported to have beneficial effects on plant growth and development under salt stress. However, the mechanism is still poorly understood. In an attempt to identify genes or gene networks that may be orchestrated to improve salt tolerance of cucumber plants, we sequenced the transcriptomes of both control and salt-stressed cucumber leaves in the presence or absence of added Si. Seedlings of cucumber 'JinYou 1' were subjected to salt stress (75 mM NaCl) without or with addition of 0.3 mM Si. Plant growth, photosynthetic gas exchange and transcriptomic dynamics were investigated. The results showed that Si addition improved the growth and photosynthetic performance of cucumber seedlings under salt stress. The comparative transcriptome analysis revealed that Si played an important role in shaping the transcriptome of cucumber: the expressions of 1469 genes were altered in response to Si treatment in the control conditions, and these genes were mainly involved in ion transport, hormone and signal transduction, biosynthetic and metabolic processes, and stress and defense responses. Under salt stress alone, 1482 genes with putative functions associated with metabolic processes and responses to environmental stimuli have changed their expression levels. Si treatment shifted the transcriptome of salt-stressed cucumber back to that of the control, as evidenced that among the 708 and 774 genes that were up- or down-regulated under salt stress, a large majority of them (609 and 595, respectively) were reverted to the normal expression levels. These results suggest that Si may act as an elicitor to precondition cucumber plants and induce salt tolerance. The study may help us understand the mechanism for silicon-mediated salt tolerance and provide a theoretical basis for silicon application in crop production in saline soils.


Assuntos
Cucumis sativus/efeitos dos fármacos , Estresse Salino/efeitos dos fármacos , Silicatos/farmacologia , Transcriptoma/efeitos dos fármacos , Cucumis sativus/genética , Cucumis sativus/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Modelos Teóricos , Fotossíntese/efeitos dos fármacos , Fotossíntese/genética , Desenvolvimento Vegetal/efeitos dos fármacos , Desenvolvimento Vegetal/genética , Salinidade , Estresse Salino/genética , Tolerância ao Sal/efeitos dos fármacos , Tolerância ao Sal/genética , Cloreto de Sódio/administração & dosagem
20.
Ecotoxicol Environ Saf ; 169: 8-17, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30412897

RESUMO

Silicon can increase salt tolerance, but the underlying mechanism has remained unclear. Here, we investigated the effect of silicon on polyamine metabolism and the role of polyamine accumulation in silicon-mediated salt tolerance in cucumber. Seedlings of cucumber 'JinYou 1' were subjected to salt stress (75 mM NaCl) in the presence or absence of added 0.3 mM silicon. Plant growth, polyamine metabolism and effects of exogenous polyamines and polyamine synthesis inhibitor dicyclohexylammonium sulphate on oxidative damage were investigated. The results showed that salt stress inhibited plant growth and decreased leaf chlorophyll levels and the maximum quantum yield of PSII, and added silicon ameliorated these negative effects. Salt stress increased polyamine accumulation in the leaves and roots. Compared with salt stress alone, overall, silicon addition decreased free putrescine concentrations, but increased spermidine and spermine concentrations in both leaves and roots under salt stress. Silicon application resulted in increased polyamine levels under salt stress by promoting the activities of S-adenosylmethionine decarboxylase and arginine decarboxylase while inhibiting the activity of diamine oxidase. Exogenous application of spermidine and spermine alleviated salt-stress-induced oxidative damage, whereas polyamine synthesis inhibitor eliminated the silicon-mediated decrease in oxidative damage. The results suggest that silicon-enhanced polyamine accumulation in cucumber under salt stress may play a role in decreasing oxidative damage and therefore increase the salt tolerance.


Assuntos
Cucumis sativus/efeitos dos fármacos , Poliaminas/metabolismo , Plantas Tolerantes a Sal/efeitos dos fármacos , Silício/farmacologia , Clorofila/metabolismo , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Putrescina/metabolismo , Tolerância ao Sal , Plantas Tolerantes a Sal/crescimento & desenvolvimento , Plantas Tolerantes a Sal/metabolismo , Espermidina/metabolismo , Espermina/metabolismo
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