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1.
Cell Commun Signal ; 22(1): 299, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811954

RESUMO

Eph receptors constitute the largest family of receptor tyrosine kinases, comprising 14 distinct members classified into two subgroups: EphAs and EphBs.. Despite their essential functions in normal physiological processes, accumulating evidence suggests that the involvement of the Eph family in cancer is characterized by a dual and often contradictory nature. Research indicates that Eph/ephrin bidirectional signaling influences cell-cell communication, subsequently regulating cell migration, adhesion, differentiation and proliferation. The contradictory functionalities may arise from the diversity of Eph signaling pathways and the heterogeneity of different cancer microenvironment. In this review, we aim to discuss the dual role of the Eph receptors in tumor development, attempting to elucidate the paradoxical functionality through an exploration of Eph receptor signaling pathways, angiogenesis, immune responses, and more. Our objective is to provide a comprehensive understanding of the molecular mechanisms underlying tumor development. Additionally, we will explore the evolving landscape of utilizing Eph receptors as potential targets for tumor therapy and diagnostic tools.


Assuntos
Neoplasias , Neovascularização Patológica , Receptores da Família Eph , Transdução de Sinais , Humanos , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/imunologia , Neovascularização Patológica/metabolismo , Receptores da Família Eph/metabolismo , Animais , Progressão da Doença , Imunidade , Angiogênese
2.
Entropy (Basel) ; 25(12)2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38136528

RESUMO

Compressed sensing (CS) is a popular data compression theory for many computer vision tasks, but the high reconstruction complexity for images prevents it from being used in many real-world applications. Existing end-to-end learning methods achieved real time sensing but lack theory guarantee for robust reconstruction results. This paper proposes a neural network called RootsNet, which integrates the CS mechanism into the network to prevent error propagation. So, RootsNet knows what will happen if some modules in the network go wrong. It also implements real-time and successfully reconstructed extremely low measurement rates that are impossible for traditional optimization-theory-based methods. For qualitative validation, RootsNet is implemented in two real-world measurement applications, i.e., a near-field microwave imaging system and a pipeline inspection system, where RootsNet easily saves 60% more measurement time and 95% more data compared with the state-of-the-art optimization-theory-based reconstruction methods. Without losing generality, comprehensive experiments are performed on general datasets, including evaluating the key components in RootsNet, the reconstruction uncertainty, quality, and efficiency. RootsNet has the best uncertainty performance and efficiency, and achieves the best reconstruction quality under super low-measurement rates.

3.
Sensors (Basel) ; 22(13)2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35808186

RESUMO

For the alignment problem of strapdown inertial navigation system (SINS) under the complex environment of unknown latitude, angular oscillation interference, and line interference, the ant colony simulated annealing algorithm of gravity vector optimization is proposed to obtain the gravity apparent motion vector optimization equation, and the polynomial fitting method is proposed to simultaneously perform latitude estimation and self-alignment in combination with the alignment principle of SINS. Simulations and experiments show that the proposed method has more robust anti-interference capability than the traditional interference-based alignment method, the latitude estimation accuracy is improved by six times, the self-alignment yaw angle error RMSE value after obtaining the latitude is within 0.7°, and the roll angle and pitch angle error values are within 0.1°.

4.
Clin Exp Ophthalmol ; 49(6): 550-559, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34032343

RESUMO

BACKGROUND: To compare the postoperative complications and visual outcomes of big-bubble deep anterior lamellar keratoplasty (BB-DALK) and penetrating keratoplasty (PK) for fungal keratitis (FK). METHODS: This retrospective study included 94 cases of BB-DALK for FK and 161 cases of PK for FK from a tertiary ophthalmology care centre. RESULTS: The most common FK pathogens were Fusarium (n = 84, 32.9%) and Aspergillus (n = 67, 26.3%). The recurrence rates after BB-DALK and PK were 3.2 and 5%, respectively (p = 0.723). The follow-up duration was 31.9 ± 15.8 months in the BB-DALK group and 33.9 ± 15.0 months in the PK group. The immune rejection rate was significantly lower in the BB-DALK group than in the PK group (1.1 vs. 18.6%, p < 0.001), as was the incidence of secondary glaucoma (p = 0.018). Endothelial cell density in the BB-DALK group tended to be stable at postoperative month 6, whereas the PK group still attenuated at a hyper-physiological rate. Postoperative best-corrected visual acuity (BCVA) significantly improved in both groups (p < 0.001). No significant difference between-group was observed in BCVA, refractive cylinder, and spherical equivalent postoperatively. CONCLUSION: Big-bubble DALK is a useful and safe alternative to PK for medically uncontrolled FK.


Assuntos
Transplante de Córnea , Úlcera da Córnea , Humanos , Ceratoplastia Penetrante , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual
5.
Appl Opt ; 59(29): 9272-9278, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33104642

RESUMO

In dual or multiwavelength interferometry, the traditional equivalent wavelength method is widely used for phase recovery to enlarge the unambiguous measurement range (UMR). In fact, however, this method ignores information of size and sign (positive or negative) of single wavelength wrapped phases, and the extension of the UMR is not sufficient. For the reflective measurement, the largest UMR of the dual or multiwavelength interferometry is half of the least-common multiple (LCM) of single wavelengths, called the LCM effective wavelength, which is often several times the equivalent wavelength. But why do we often use the equivalent wavelength and seldom use the larger UMR in practice? Existing research reveals that the actual UMR is related to the measurement error of single-wavelength-wrapped phases, and half of the LCM effective wavelength is only the theoretical value. But how do errors affect the UMR? We think the quantitative analysis and description are lacking. In this paper, we continue to study this problem, analyze it in a graphical method, and give quantitative descriptions. The simulation experiments are carried out and verify our analysis.

6.
Proc Natl Acad Sci U S A ; 114(36): E7574-E7582, 2017 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-28827360

RESUMO

l-Serine biosynthesis, a crucial metabolic process in most domains of life, is initiated by d-3-phosphoglycerate (d-3-PG) dehydrogenation, a thermodynamically unfavorable reaction catalyzed by d-3-PG dehydrogenase (SerA). d-2-Hydroxyglutarate (d-2-HG) is traditionally viewed as an abnormal metabolite associated with cancer and neurometabolic disorders. Here, we reveal that bacterial anabolism and catabolism of d-2-HG are involved in l-serine biosynthesis in Pseudomonas stutzeri A1501 and Pseudomonas aeruginosa PAO1. SerA catalyzes the stereospecific reduction of 2-ketoglutarate (2-KG) to d-2-HG, responsible for the major production of d-2-HG in vivo. SerA combines the energetically favorable reaction of d-2-HG production to overcome the thermodynamic barrier of d-3-PG dehydrogenation. We identified a bacterial d-2-HG dehydrogenase (D2HGDH), a flavin adenine dinucleotide (FAD)-dependent enzyme, that converts d-2-HG back to 2-KG. Electron transfer flavoprotein (ETF) and ETF-ubiquinone oxidoreductase (ETFQO) are also essential in d-2-HG metabolism through their capacity to transfer electrons from D2HGDH. Furthermore, while the mutant with D2HGDH deletion displayed decreased growth, the defect was rescued by adding l-serine, suggesting that the D2HGDH is functionally tied to l-serine synthesis. Substantial flux flows through d-2-HG, being produced by SerA and removed by D2HGDH, ETF, and ETFQO, maintaining d-2-HG homeostasis. Overall, our results uncover that d-2-HG-mediated coupling between SerA and D2HGDH drives bacterial l-serine synthesis.


Assuntos
Oxirredutases do Álcool/metabolismo , Fosfoglicerato Desidrogenase/metabolismo , Pseudomonas aeruginosa/metabolismo , Pseudomonas stutzeri/metabolismo , Serina/metabolismo , Flavoproteínas Transferidoras de Elétrons/metabolismo , Homeostase/fisiologia , Ácidos Cetoglutáricos/metabolismo , Oxirredução
7.
J Biol Chem ; 293(40): 15513-15523, 2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-30131334

RESUMO

Pseudomonas is a very large bacterial genus in which several species can use d-malate for growth. However, the enzymes that can metabolize d-malate, such as d-malate dehydrogenase, appear to be absent in most Pseudomonas species. d-3-Phosphoglycerate dehydrogenase (SerA) can catalyze the production of d-2-hydroxyglutarate (d-2-HG) from 2-ketoglutarate to support d-3-phosphoglycerate dehydrogenation, which is the initial reaction in bacterial l-serine biosynthesis. In this study, we show that SerA of the Pseudomonas stutzeri strain A1501 reduces oxaloacetate to d-malate and that d-2-HG dehydrogenase (D2HGDH) from P. stutzeri displays d-malate-oxidizing activity. Of note, D2HGDH participates in converting a trace amount of d-malate to oxaloacetate during bacterial l-serine biosynthesis. Moreover, D2HGDH is crucial for the utilization of d-malate as the sole carbon source for growth of P. stutzeri A1501. We also found that the D2HGDH expression is induced by the exogenously added d-2-HG or d-malate and that a flavoprotein functions as a soluble electron carrier between D2HGDH and electron transport chains to support d-malate utilization by P. stutzeri These results support the idea that D2HGDH evolves as an enzyme for both d-malate and d-2-HG dehydrogenation in P. stutzeri In summary, D2HGDH from P. stutzeri A1501 participates in both a core metabolic pathway for l-serine biosynthesis and utilization of extracellular d-malate.


Assuntos
Oxirredutases do Álcool/metabolismo , Proteínas de Bactérias/metabolismo , Malatos/metabolismo , Pseudomonas stutzeri/enzimologia , Serina/metabolismo , Oxirredutases do Álcool/genética , Proteínas de Bactérias/genética , Transporte de Elétrons , Ensaios Enzimáticos , Expressão Gênica , Glutaratos/metabolismo , Ácidos Glicéricos/metabolismo , Ácidos Cetoglutáricos/metabolismo , Cinética , Ácido Oxaloacético/metabolismo , Oxirredução , Pseudomonas stutzeri/genética , Estereoisomerismo , Especificidade por Substrato
8.
J Microsc ; 276(3): 118-127, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31696930

RESUMO

White light interferometry (WLI) is an effective and widely-used technique for structured surface measurement. However, it requires multiframe interferograms with vertical scanning to realise large-scale measurement, which is time consuming and computationally intensive. This paper proposes a rapid surface measurement method to realise surface recovery with a single interferogram by white light interferometry. First, the feasibility to solve the wrapped phase of a single white-light interferogram by Hilbert transform is certified. Then, unwrapped phases against zero optical path difference position (OPD) are achieved by a zero optical path difference detection algorithm applied to unwrapping process, which provides efficient surface recovery. To ensure the accuracy of phase solution in the proposed method, the necessary number and width of the interference fringes in the interferogram are analysed and determined based on Hilbert transform and sampling analysis. Finally, measurement results of a standard step sample and a standard reticle template are presented, which prove the accuracy and efficiency of the proposed method. LAY DESCRIPTION: As an effective and widely-used technique for structured surface measurement, white light interferometry (WLI) has the major advantage to measure noncontinuous surfaces using the short coherence length of a wide bandwidth source. However, frequently vertical scanning is required to get series of white light interferograms at different axial positions for surface recovery by recovered algorithms. The vertical scanning process is complicated and time consuming. This paper proposes a fast and efficient method to realise rapid surface measurement using only a single-frame interferogram based on WLI. First, the feasibility of using only one single white light interferogram to solve wrapped phases by Hilbert transform (HT) is discussed. Next, unwrapping process and zero optical path difference(OPD) detection algorithms are combined to unwrap phases against zero OPD position, which makes the structured surface recovery much easier. After that, the feasible number and width of interference fringes are determined based on sampling analysis and HT to guarantee the reliability and accuracy of phase solution in the proposed method. Finally, the accuracy and efficiency of this method is verified by measurement experiments of a standard step sample and a standard reticle template.

9.
Appl Opt ; 58(6): 1327-1335, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30874013

RESUMO

Simultaneous phase-shifting interferometry (SPSI) is a suitable technique for dynamic surface measurement due to its rapid measurement capability. Based on whether there are obvious multiple phase-shifting channels in the setup, it can be divided into the multi-channel type and the pixelated phase-mask type. For the former type, two important error sources are the uneven intensity distribution among different phase-shifting channels and inaccurate phase shifts in each phase-shifting channel. In order to diminish the influence of these two error sources, several methods have been proposed. However, in some of these methods, only one error source of the two was considered and corrected. In the methods where the two error sources were both considered, some assumptions such as the uniform background intensity and fringe contrast are needed, so a complete and universal suppression method for both error sources is still needed in actual applications. In this paper, for a prism-based SPSI, we proposed such an error-correction method that mainly contains the following contributions. First, the intrinsic parameters of the system, including intensity distribution coefficients and relative phase shifts among phase-shifting channels, are calibrated in advance. We also checked the uniformity of phase shifts in each phase-shifting channel. Second, based on the obtained parameters, a corrected four-step phase-shifting algorithm is deduced to recover the more accurate measured phase. Results of both simulation and experiment verify the effectiveness of the proposed method.

10.
J Bacteriol ; 199(22)2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28847921

RESUMO

Bacterial membrane-associated NAD-independent d-lactate dehydrogenase (Fe-S d-iLDH) oxidizes d-lactate into pyruvate. A sequence analysis of the enzyme reveals that it contains an Fe-S oxidoreductase domain in addition to a flavin adenine dinucleotide (FAD)-containing dehydrogenase domain, which differs from other typical d-iLDHs. Fe-S d-iLDH from Pseudomonas putida KT2440 was purified as a His-tagged protein and characterized in detail. This monomeric enzyme exhibited activities with l-lactate and several d-2-hydroxyacids. Quinone was shown to be the preferred electron acceptor of the enzyme. The two domains of the enzyme were then heterologously expressed and purified separately. The Fe-S cluster-binding motifs predicted by sequence alignment were preliminarily verified by site-directed mutagenesis of the Fe-S oxidoreductase domain. The FAD-containing dehydrogenase domain retained 2-hydroxyacid-oxidizing activity, although it decreased compared to the full Fe-S d-iLDH. Compared to the intact enzyme, the FAD-containing dehydrogenase domain showed increased catalytic efficiency with cytochrome c as the electron acceptor, but it completely lost the ability to use coenzyme Q10 Additionally, the FAD-containing dehydrogenase domain was no longer associated with the cell membrane, and it could not support the utilization of d-lactate as a carbon source. Based on the results obtained, we conclude that the Fe-S oxidoreductase domain functions as an electron transfer component to facilitate the utilization of quinone as an electron acceptor by Fe-S d-iLDH, and it helps the enzyme associate with the cell membrane. These functions make the Fe-S oxidoreductase domain crucial for the in vivo d-lactate utilization function of Fe-S d-iLDH.IMPORTANCE Lactate metabolism plays versatile roles in most domains of life. Lactate utilization processes depend on certain enzymes to oxidize lactate to pyruvate. In recent years, novel bacterial lactate-oxidizing enzymes have been continually reported, including the unique NAD-independent d-lactate dehydrogenase that contains an Fe-S oxidoreductase domain besides the typical flavin-containing domain (Fe-S d-iLDH). Although Fe-S d-iLDH is widely distributed among bacterial species, the investigation of it is insufficient. Fe-S d-iLDH from Pseudomonas putida KT2440, which is the major d-lactate-oxidizing enzyme for the strain, might be a representative of this type of enzyme. A study of it will be helpful in understanding the detailed mechanisms underlying the lactate utilization processes.


Assuntos
Flavina-Adenina Dinucleotídeo/metabolismo , Proteínas Ferro-Enxofre/metabolismo , Lactato Desidrogenases/genética , Lactato Desidrogenases/metabolismo , Ácido Láctico/metabolismo , Quinonas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Coenzimas , Citocromos c/metabolismo , Elétrons , Lactato Desidrogenases/isolamento & purificação , Mutagênese Sítio-Dirigida , NAD/metabolismo , Oxirredução , Pseudomonas putida/enzimologia , Ubiquinona/análogos & derivados , Ubiquinona/metabolismo
11.
J Am Chem Soc ; 138(26): 8076-9, 2016 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-27310487

RESUMO

Exploration of heterogeneous molecular catalysts combining the atomic-level tunability of molecular structures and the practical handling advantages of heterogeneous catalysts represents an attractive approach to developing high-performance catalysts for important and challenging chemical reactions such as electrochemical carbon dioxide reduction which holds the promise for converting emissions back to fuels utilizing renewable energy. Thus, far, efficient and selective electroreduction of CO2 to deeply reduced products such as hydrocarbons remains a big challenge. Here, we report a molecular copper-porphyrin complex (copper(II)-5,10,15,20-tetrakis(2,6-dihydroxyphenyl)porphyrin) that can be used as a heterogeneous electrocatalyst with high activity and selectivity for reducing CO2 to hydrocarbons in aqueous media. At -0.976 V vs the reversible hydrogen electrode, the catalyst is able to drive partial current densities of 13.2 and 8.4 mA cm(-2) for methane and ethylene production from CO2 reduction, corresponding to turnover frequencies of 4.3 and 1.8 molecules·site(-1)·s(-1) for methane and ethylene, respectively. This represents the highest catalytic activity to date for hydrocarbon production over a molecular CO2 reduction electrocatalyst. The unprecedented catalytic performance is attributed to the built-in hydroxyl groups in the porphyrin structure and the reactivity of the copper(I) metal center.

12.
Cancer Lett ; 582: 216567, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38070822

RESUMO

EphB1 is implicated in numerous physiological and pathological processes, including nervous system diseases, cardiovascular diseases and cancers. It binds to membrane-bound ligands and drives bidirectional signaling. EphB1, along with its ligand ehrinB, plays a pivotal role in activating immune cells. However, despite its presence in dendritic cells (DCs), EphB1's involvement in the differentiation and maturation of DCs in cancers remains inadequately understood. In this study, we found compromised differentiation and maturation of DCs in EphB1-/- mice bearing lung adenocarcinoma syngeneic tumors. Our in vitro assays revealed that EphB1 phosphorylation induced DC differentiation and maturation. Cox-2, a key enzyme involved in the production of proinflammatory molecules, is implicated in DC differentiation induced by phosphorylated EphB1. Additionally, the study has identified lead compounds that specifically target EphB1 phosphorylation sites. Collectively, this research on EphB1 phosphorylation has provided valuable insights into the regulation of immune cell functionality and holds the potential for the development of innovative therapeutic strategies for a range of diseases.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Camundongos , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Transdução de Sinais , Diferenciação Celular , Células Dendríticas
13.
ISA Trans ; 143: 221-230, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37730462

RESUMO

In this paper, a brain-like navigation scheme based on fuzzy kernel C-means (FKCM) clustering assisted pyramid Lucas Kanade (LK) optical flow algorithm is developed to measure the position of vehicle. The Speed Cell and Place Cell in animals' brain are introduced to construct the brain-like navigation mechanism which involves the optical flow method and image template matching to imitate the cells above-mentioned separately. To eliminate the singular values during optical flow calculation, the output of pyramid LK algorithm is clustered by FKCM algorithm firstly. Then, the velocity is calculated and integrated to get the position of the vehicle, and the brain-like navigation scheme is introduced to correct the position measurement errors by eliminating the accumulated errors resulting from velocity integration. The prominent advantages of the presented method are: (i) a pure visual brain-like position measurement method based on the concept of speed cells and place cells is proposed, making visual navigation more accurate and intelligent; (ii) the FKCM algorithm is used to eliminate the singular value of the pyramid LK algorithm, which improves the calculated velocity accuracy. Also, experimental comparison with classical pyramid LK algorithm is given to illustrate the superiority of the proposed method in position measurement.

14.
Materials (Basel) ; 15(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36079259

RESUMO

Carbon fiber-reinforced polymer (CFRP) is a widely-used composite material that is vulnerable to impact damage. Light impact damages destroy the inner structure but barely show obvious change on the surface. As a non-contact and high-resolution method to detect subsurface and inner defect, near-field radiofrequency imaging (NRI) suffers from high imaging times. Although some existing works use compressed sensing (CS) for a faster measurement, the corresponding CS reconstruction time remains high. This paper proposes a deep learning-based CS method for fast NRI, this plugin method decreases the measurement time by one order of magnitude without hardware modification and achieves real-time imaging during CS reconstruction. A special 0/1-Bernoulli measurement matrix is designed for sensor scanning firstly, and an interpretable neural network-based CS reconstruction method is proposed. Besides real-time reconstruction, the proposed learning-based reconstruction method can further reduce the required data thus reducing measurement time more than existing CS methods. Under the same imaging quality, experimental results in an NRI system show the proposed method is 20 times faster than traditional raster scan and existing CS reconstruction methods, and the required data is reduced by more than 90% than existing CS reconstruction methods.

15.
J Mater Chem B ; 10(48): 10042-10053, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36156670

RESUMO

Ceria nanoparticles are remarkable antioxidants due to their large cerium(III) content and the possibility of recovering cerium(III) from cerium(IV) after reaction. Here we increase the cerium(III) content of colloidally stable nanoparticles (e.g., nanocrystals) using a reactive polymeric surface coating. Catechol-grafted poly(ethylene glycols) (PEG) polymers of varying lengths and architectures yield materials that are non-aggregating in a variety of aqueous media. Cerium(IV) on the ceria surface both binds and oxidizes the catechol functionality, generating a dark-red colour emblematic of surface-oxidized catechols with a concomitant increase in cerium(III) revealed by X-ray photoemission spectroscopy (XPS). The extent of ceria reduction depends sensitively on the architecture of the coating polymer; small and compact polymer chains pack with high density at the nanoparticle surface yielding the most cerium(III). Nanoparticles with increased surface reduction, quantified by the intensity of their optical absorption and thermogravimetric measures of polymer grafting densities, were more potent antioxidants as measured by a standard TEAC antioxidant assay. For the same core composition nanoparticle antioxidant capacities could be increased over an order of magnitude by tailoring the length and architecture of the reactive surface coatings.


Assuntos
Cério , Nanopartículas , Polietilenoglicóis/química , Antioxidantes , Nanopartículas/química , Cério/química , Catecóis/química , Polímeros
16.
Neural Netw ; 142: 573-582, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34343781

RESUMO

For the context-dependent Text-to-SQL task, the generation of SQL query is placed in a multi-turn interaction scenario. Each turn of Text-to-SQL must take historical interactive information and database schema into account. Accordingly, how to encode and integrate these different types of texts (the question sentence, the corresponding SQL query, and database schema) is a tough problem. In previous work, these series of texts are usually concatenated into sequences and encoded by various variants of recurrent neural networks (RNN). However, the RNNs cannot model the intrinsic relationship of the text directly. To this end, we propose an interaction-modeling mechanism to represent and aggregate these texts. Firstly, different types of texts are represented as individual graphs. Then, heterogeneous graph aggregation is used to capture the interactions and aggregate graphs into a holistic representation. Finally, the corresponding SQL query is generated based on the current question and the aggregated information. We evaluate our model on the SparC and CoSQL dataset to demonstrate the benefits of interaction-modeling. Experimentally, our model has a competitive performance and space-time cost.


Assuntos
Idioma , Redes Neurais de Computação , Bases de Dados Factuais
17.
Nat Commun ; 12(1): 7108, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876568

RESUMO

D-2-Hydroxyglutarate (D-2-HG) is a metabolite involved in many physiological metabolic processes. When D-2-HG is aberrantly accumulated due to mutations in isocitrate dehydrogenase or D-2-HG dehydrogenase, it functions in a pro-oncogenic manner and is thus considered a therapeutic target and biomarker in many cancers. In this study, DhdR from Achromobacter denitrificans NBRC 15125 is identified as an allosteric transcriptional factor that negatively regulates D-2-HG dehydrogenase expression and responds to the presence of D-2-HG. Based on the allosteric effect of DhdR, a D-2-HG biosensor is developed by combining DhdR with amplified luminescent proximity homogeneous assay (AlphaScreen) technology. The biosensor is able to detect D-2-HG in serum, urine, and cell culture medium with high specificity and sensitivity. Additionally, this biosensor is used to identify the role of D-2-HG metabolism in lipopolysaccharide biosynthesis of Pseudomonas aeruginosa, demonstrating its broad usages.


Assuntos
Oxirredutases do Álcool/metabolismo , Técnicas Biossensoriais , Regulação da Expressão Gênica , Glutaratos/química , Glutaratos/metabolismo , Achromobacter denitrificans/enzimologia , Achromobacter denitrificans/genética , Achromobacter denitrificans/metabolismo , Oxirredutases do Álcool/genética , Bactérias/metabolismo , Células HEK293 , Humanos , Isocitrato Desidrogenase , Redes e Vias Metabólicas , Mutação , Neoplasias , Fatores de Transcrição
18.
Adv Healthc Mater ; 10(11): e2001780, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33882196

RESUMO

Millions of people a year receive magnetic resonance imaging (MRI) contrast agents for the diagnosis of conditions as diverse as fatty liver disease and cancer. Gadolinium chelates, which provide preferred T1 contrast, are the current standard but face an uncertain future due to increasing concerns about their nephrogenic toxicity as well as poor performance in high-field MRI scanners. Gadolinium-containing nanocrystals are interesting alternatives as they bypass the kidneys and can offer the possibility of both intracellular accumulation and active targeting. Nanocrystal contrast performance is notably limited, however, as their organic coatings block water from close interactions with surface Gadoliniums. Here, these steric barriers to water exchange are minimized through shape engineering of plate-like nanocrystals that possess accessible Gadoliniums at their edges. Sulfonated surface polymers promote second-sphere relaxation processes that contribute remarkable contrast even at the highest fields (r1 = 32.6 × 10-3 m Gd-1 s-1 at 9.4 T). These noncytotoxic materials release no detectable free Gadolinium even under mild acidic conditions. They preferentially accumulate in the liver of mice with a circulation half-life 50% longer than commercial agents. These features allow these T1 MRI contrast agents to be applied for the first time to the ex vivo detection of nonalcoholic fatty liver disease in mice.


Assuntos
Gadolínio , Nanopartículas , Animais , Meios de Contraste , Imageamento por Ressonância Magnética , Camundongos
19.
ACS Appl Mater Interfaces ; 12(37): 41932-41941, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32812740

RESUMO

Multicore iron oxide nanoparticles, also known as colloidal nanocrystal clusters, are magnetic materials with diverse applications in biomedicine and photonics. Here, we examine how both of their characteristic dimensional features, the primary particle and sub-micron colloid diameters, influence their magnetic properties and performance in two different applications. The characterization of these basic size-dependent properties is enabled by a synthetic strategy that provides independent control over both the primary nanocrystal and cluster dimensions. Over a wide range of conditions, electron microscopy and X-ray diffraction reveal that the oriented attachment of smaller nanocrystals results in their crystallographic alignment throughout the entire superstructure. We apply a sulfonated polymer with high charge density to prevent cluster aggregation and conjugate molecular dyes to particle surfaces so as to visualize their collection using handheld magnets. These libraries of colloidal clusters, indexed both by primary nanocrystal dimension (dp) and overall cluster diameter (Dc), form magnetic photonic crystals with relatively weak size-dependent properties. In contrast, their performance as MRI T2 contrast agents is highly sensitive to cluster diameter, not primary particle size, and is optimized for materials of 50 nm diameter (r2 = 364 mM-1 s-1). These results exemplify the relevance of dimensional control in developing applications for these versatile materials.


Assuntos
Meios de Contraste/química , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/química , Óptica e Fotônica , Tamanho da Partícula , Propriedades de Superfície
20.
Artigo em Inglês | MEDLINE | ID: mdl-32154242

RESUMO

Acetoin is a potential platform compound for a variety of chemicals. Bacillus licheniformis MW3, a thermophilic and generally regarded as safe (GRAS) microorganism, can produce 2,3-butanediol with a high concentration, yield, and productivity. In this study, B. licheniformis MW3 was metabolic engineered for acetoin production. After deleting two 2,3-butanediol dehydrogenases encoding genes budC and gdh, an engineered strain B. licheniformis MW3 (ΔbudCΔgdh) was constructed. Using fed-batch fermentation of B. licheniformis MW3 (ΔbudCΔgdh), 64.2 g/L acetoin was produced at a productivity of 2.378 g/[L h] and a yield of 0.412 g/g from 156 g/L glucose in 27 h. The fermentation process exhibited rather high productivity and yield of acetoin, indicating that B. licheniformis MW3 (ΔbudCΔgdh) might be a promising acetoin producer.

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