Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38
Filtrar
1.
Opt Express ; 32(3): 3891-3911, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297600

RESUMO

In pursuit of enhancing the display performance of gamut extension algorithms across diverse image types while minimizing image dependency, this study introduces a dynamic gamut extension algorithm. The algorithm is designed to extend the sRGB source gamut towards the wide gamut of a laser display. To evaluate its effectiveness, psychophysical experiments were conducted using four distinct image categories: complexions, scenery, objects, and color blocks and bars. The performance of the proposed algorithm was benchmarked against four established color gamut mapping algorithms. The comparative analysis revealed that our algorithm excels in handling wide color gamuts, outperforming the alternatives in terms of preference and the preservation of detail richness.

2.
Bioorg Chem ; 150: 107585, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38917491

RESUMO

The overexpression of PDIA1 in cancer has spurred the quest for effective inhibitors. However, existing inhibitors often bind to only one active site, limiting their efficacy. In our study, we developed a PROTAC-mimetic probe dPA by combining PACMA31 (PA) analogs with cereblon-directed pomalidomide. Through protein profiling and analysis, we confirmed dPA's specific interaction with PDIA1's active site cysteines. We further synthesized PROTAC variants with a thiophene ring and various linkers to enhance degradation efficiency. Notably, H4, featuring a PEG linker, induced significant PDIA1 degradation and inhibited cancer cell proliferation similarly to PA. The biosafety profile of H4 is comparable to that of PA, highlighting its potential for further development in cancer therapy. Our findings highlight a novel strategy for PDIA1 inhibition via targeted degradation, offering promising prospects in cancer therapeutics. This approach may overcome limitations of conventional inhibitors, presenting new avenues for advancing anti-cancer interventions.


Assuntos
Antineoplásicos , Proliferação de Células , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Sondas Moleculares/química , Sondas Moleculares/farmacologia , Sondas Moleculares/síntese química , Estrutura Molecular , Pró-Colágeno-Prolina Dioxigenase , Isomerases de Dissulfetos de Proteínas/antagonistas & inibidores , Isomerases de Dissulfetos de Proteínas/metabolismo , Relação Estrutura-Atividade , Peptídeos/química , Peptídeos/farmacologia
3.
J Environ Sci (China) ; 138: 496-505, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38135415

RESUMO

Zhuzhou was one of the most polluted cities in China with the serious acid rain. Due to the implementation of air pollution control measures from 2016 to 2018, the acid rain pollution in this city has reduced. In order to understand the recent situation, a comprehensive study on the acid rain was carried out from January 2011 to December 2020. The pH values during the study period varied from 3.3 to 7.5, with a volume-weighted mean value of 4.7. The predominant acidic components of the precipitation were SO42- and NO3-, accounting for 89.3% of the total anions. The ratio of non-sea-salt SO42- to NO3- showed a decreasing trend, revealing that the pollution type of acid rain changed from sulfuric acid type to sulfuric acid and nitric acid compound type. The correlation analysis (p < 0.05) showed that SO42- was positively correlated with NH4+, Ca2+, and Mg2+; hence, it predominated in precipitation as (NH4)2SO4, NH4HSO4, CaSO4, and MgSO4. Significant positive correlation of Ca2+ with Mg2+ shows that they may originated mainly from crust. Significant positive correlation between SO42- and F- and Cl- indicate that their source may be related to the non-ferrous metal smelting industry in Zhuzhou. Further correlation analysis shows that emissions from the non-ferrous metal smelting industry in the area have a large significant on SO42- and F- in precipitation, while Cl- may still be emitted from other anthropogenic sources.


Assuntos
Chuva Ácida , Poluentes Atmosféricos , Chuva Ácida/análise , Monitoramento Ambiental , Ânions/análise , China , Estações do Ano , Poluentes Atmosféricos/análise
4.
J Am Chem Soc ; 145(44): 24272-24283, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37899626

RESUMO

Targeted degradation of the cell-surface and extracellular proteins via the endogenous lysosomal degradation pathways, such as lysosome-targeting chimeras (LYTACs), has recently emerged as an attractive tool to expand the scope of extracellular chemical biology. Herein, we report a series of recombinant proteins genetically fused to insulin-like growth factor 2 (IGF2), which we termed iLYTACs, that can be conveniently obtained in high yield by standard cloning and bacterial expression in a matter of days. We showed that both type-I iLYTACs, in which IGF2 was fused to a suitable affibody or nanobody capable of binding to a specific protein target, and type-II iLYTAC (or IGF2-Z), in which IGF2 was fused to the IgG-binding Z domain that served as a universal antibody-binding adaptor, could be used for effective lysosomal targeting and degradation of various extracellular and membrane-bound proteins-of-interest. These heterobifunctional iLYTACs are fully genetically encoded and can be produced on a large scale from conventional E. coli expression systems without any form of chemical modification. In the current study, we showed that iLYTACs successfully facilitated the cell uptake, lysosomal localization, and efficient lysosomal degradation of various disease-relevant protein targets from different mammalian cell lines, including EGFR, PD-L1, CD20, and α-synuclein. The antitumor properties of iLYTACs were further validated in a mouse xenograft model. Overall, iLYTACs represent a general and modular strategy for convenient and selective targeted protein degradation, thus expanding the potential applications of current LYTACs and related techniques.


Assuntos
Escherichia coli , Proteínas de Membrana , Humanos , Camundongos , Animais , Proteínas de Membrana/metabolismo , Escherichia coli/metabolismo , Transdução de Sinais , Lisossomos/metabolismo , Linhagem Celular , Mamíferos/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Fator de Crescimento Insulin-Like II/farmacologia
5.
Opt Express ; 31(16): 26815-26830, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37710532

RESUMO

The color gamut volume (CGV) and light efficiency of a four-primary display system were theoretically simulated with different wavelength configuration. Given the wavelengths of the blue and red primaries, we optimized the other two primary colors; the wavelength set with the largest CGV was chosen. The maximum CGV, 2.346 × 106, was obtained at (660, 530, 507, 465) nm. The maximum light efficiency was also determined. A trade-off between CGV and light efficiency should be made according to the requirement of the devices. This study provides guidance for the construction of a four-primary laser display system and the optimization of the CGV in multi-primary display systems.

6.
Bioorg Chem ; 134: 106461, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36924654

RESUMO

Inducing cell ferroptosis by inactivating glutathione peroxidase 4 (GPX4) is a popular cancer treatment strategy. However, only few GPX4 inhibitors have been developed to date. PROteolysis Targeting Chimera (PROTAC) is a promising approach to provide new opportunities to overcome limitations of traditional therapeutics. Herein, a PROTAC-like activity-based probe PD-Q2 was first assembled using Ugi reaction, consisting of a known GPX4 inhibitor ML-162 homolog to the E3 ligase cereblon ligand-pomalidomide. Pull-down and immunoblotting analysis revealed that GPX4 was a covalent target of PD-Q2, but the degradation efficiency was weak. Therefore, a series of degraders was further synthesized by varying the linkers of heterofunctional PROTACs. Among these degraders, PD-4 and PD-P2 were found to promote effective GPX4 degradation via the ubiquitin-proteasome system and cause lipid ROS accumulation. PD-4 and PD-P2 showed potent inhibitory of colony formation and cell growth. Furthermore, we found that with pomalidomide, the degraders exhibit a high fluorescent signal that is mostly localized in the lysosome, which may affect the effectiveness of anti-cell proliferation. Overall, we provide GPX4 degraders for further exploring therapeutic potential of regulating ferroptosis.


Assuntos
Quimera de Direcionamento de Proteólise , Ciclo Celular , Proliferação de Células , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Proteólise
7.
Bioorg Chem ; 141: 106908, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37827016

RESUMO

Lysosome-targeting chimeras (LYTACs) have emerged as a promising technique to extend the scope of targeted protein degradation to extracellular proteins, e.g., secreted proteins and membrane-anchored proteins. However, up to now, only a small number of lysosomal targeting receptors (LTRs), such as cation-independent mannose 6-phosphate receptor (CI-M6PR) and asialoglycoprotein receptor (ASGPR), were reported to build LYTACs for degradation of extracellular proteins. Therefore, it is important to explore more functionalized ligands for the relevant LTRs to expand the LYTAC framework. Herein, we demonstrate a new LTR ligand-glucagon like peptide 1 (GLP-1) based targeted degradation platform, termed GLP-1 receptor-targeting chimeras (GLP-1-LYTAC). GLP-1-LYTACs are formed by conjugating GLP-1 with targeted binder (such as antibody) through Click Chemistry, showing efficiently lysosomal degradation of both extracellular proteins (GFP and Neutravidin) as well as cell membrane proteins (EGFR and PD-L1). We believe that this novel GLP-1-LYTAC will open up a new dimension for targeted protein breakdown.


Assuntos
Peptídeo 1 Semelhante ao Glucagon , Proteólise
8.
Appl Opt ; 62(15): 4102-4109, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-37706723

RESUMO

This study explores the application of optical fiber lasers in display systems by integrating a P r3+-doped green all-fiber laser into a laser projection display system. As a control group to compare the results, a 520 nm semiconductor green laser diode module was integrated, similar to the experimental group. The color gamut and speckle performances were studied and compared. The results showed that the experimental group performed slightly better in the color gamut volume. The speckle contrast decreased rapidly in the experimental group when power increased. To our knowledge, this is the first study to apply a fiber laser to a laser display system. The results shed light on developing laser display systems with fewer or no speckle reduction elements.

9.
Anal Chem ; 94(20): 7272-7277, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35549110

RESUMO

Nitroreductase (NTR), one of the flavin-dependent enzymes and an upregulated enzyme under tumor hypoxia, has been studied for decades. Many fluorescent probes were developed to detect NTR activity; however, these probes tend to diffuse away from their reaction site (NTR) inevitably, leading to inappropriate sample fixation, lower accuracy of NTR localization, and weaker signal-to-noise ratio. Herein, we present the design, synthesis, in vitro evaluation, and biological applications of an NTR-activatable fluorogenic and labeling probe FY. By integrating with quinone methide (QM) proximity-based protein labeling, the additional fluoromethyl group on FY serves as a potential origin of QM. Compared with conventional fluorescent probes, this new NTR probe not only offers mitochondrial localizable and fluorogenic response but also achieves permanent retention on the site of activation with an enhanced spatial resolution to improve the detection sensitivity even after cell fixation. We believe our work could offer an expandable synthetic approach to develop these permanent labeling and imaging fluorescence probes for deciphering complex biological events.


Assuntos
Corantes Fluorescentes , Nitrorredutases , Microscopia de Fluorescência , Mitocôndrias/metabolismo , Nitrorredutases/metabolismo , Hipóxia Tumoral
10.
Opt Express ; 30(8): 13356-13371, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35472950

RESUMO

We propose and demonstrate a resolution-preserving passive 2D/3D convertible display by two individual wavelengths. It uses a holographic optical element to generate two images and passively separate the exit pupils for these two wavelengths, which forms two viewpoints for each of the observer's eyes. Due to Bragg-mismatched reconstruction of two similar but distinct wavelengths, the images are separated in space. They can be fused into one through the convergence function of human eyes. By switching the input image source, the conversion between 2D and 3D mode can be realized. This method is resolution-preserving and 2D/3D convertible with no extra active components. For experimental verification, a proof-of-concept projection-type prototype is assessed.

11.
Opt Express ; 30(2): 1036-1055, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35209248

RESUMO

For a display system, a wide-color gamut can significantly improve the viewing experience. It is known that an ultra-wide color gamut can be achieved using more primaries. However, for multi-primary displays (MPDs), choosing the parameters of the primaries (e.g., wavelength and luminance) is not trivial because the necessary theoretical foundation is still lacking. In this study, starting from three-primary display, we proposed a method for calculating all possible peak luminances of MPDs. This is done by mathematically representing the added new primaries with the original three primaries. Of all the possible results, by optimizing the peak luminance of each primary color, the theoretical gamut volume satisfying specific requirements could be obtained. The method provided can be extended to N primaries (N > 6). Using this method, we have successfully built a six-primary display system and used it to verify the validity of the method. Combined with the calculation of color gamut volume, the theoretical framework provided can be used to guide the selection of wavelength, spectrum width, and luminances of primaries in MPDs.

12.
Opt Express ; 30(18): 33374-33394, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36242377

RESUMO

We propose and demonstrate a color-speckle assessment method based on a three-dimensional Jzazbz color space, which is appropriate for both three-primary and multi-primary systems. In the proposed scheme, new physical quantities are defined to describe the color-speckle characteristics, which provides a general and intuitive color-speckle evaluation for different laser projectors. Experimental verification is also performed using three-primary and six-primary laser projectors. The simulation and measurement results are consistent.

13.
Opt Express ; 30(21): 38938-38952, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36258446

RESUMO

To improve the color rendering ability in yellow color regions, the inclusion of yellow among the primary colors is commonly proposed. In this study, an algorithm for evaluating gamut enhancement in yellow regions is developed. The performance of different wavelength sets of RGBY four-primary system is studied theoretically in terms of various aspects, including the color gamut volume, gamut coverages, and gamut enhancement ratio in yellow regions. The optimal wavelength set and its optimal luminance ratio are then determined. This research provides strong guidance for the construction of practical four-primary-laser display systems.

14.
Opt Express ; 30(20): 36576-36591, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36258583

RESUMO

Based on the difference between multi-primary displays (MPDs) and three-primary displays, we propose a new definition for evaluating the color gamut volume (CGV) to explore the upper limit of MPDs, which could theoretically represent all colors that MPDs can display. The proposed definition corrects the defects in the L*a*b* color space that arise when calculating the CGV of MPDs. In view of the high computational complexity of this method, we propose a simplified scheme with a small margin of error. Additionally, we verify the new definition with experiments on a six-primary projector. This method is helpful in guiding the selection of light sources and the evaluation of MPDs, and also has great reference value to calculate the target gamut for gamut mapping in MPDs.

15.
Acta Biochim Biophys Sin (Shanghai) ; 51(7): 723-733, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31168565

RESUMO

Armadillo repeat containing 1 (ARC1) is phosphorylated by S-locus receptor kinase (SRK) and functions as a positive regulator in self-incompatibility response of Brassica. However, ARC1 only causes partial breakdown of the self-incompatibility response, and other SRK downstream factors may also participate in the self-incompatibility signaling pathway. In the present study, to search for SRK downstream targets, a plant U-box protein 3 (BoPUB3) was identified from the stigma of Brassica oleracea L. BoPUB3 was highly expressed in the stigma, and its expression was increased with the stigma development and reached to the highest level in the mature-stage stigma. BoPUB3, a 76.8-kDa protein with 697 amino acids, is a member of the PUB-ARM family and contains three domain characteristics of BoARC1, including a U-box N-terminal domain, a U-box motif, and a C-terminal arm repeat domain. The phylogenic tree showed that BoPUB3 was close to BoARC1. The synteny analysis revealed that B. oleracea chromosomal region containing BoPUB3 had high synteny with the Arabidopsis thaliana chromosomal region containing AtPUB3 (At3G54790). In addition, the subcellular localization analysis showed that BoPUB3 primarily localized in the plasma membrane and also in the cytoplasm. The combination of the yeast two-hybrid and in vitro binding assay showed that both BoPUB3 and BoARC1 could interact with SRK kinase domain, and SRK showed much higher level of ß-galactosidase activity in its interaction with BoPUB3 than with BoARC1. These results implied that BoPUB3 is a novel interactor with SRK, which lays a basis for further research on whether PUB3 participates in the self-incompatibility signaling pathway.


Assuntos
Brassica/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas Quinases/genética , Sequência de Aminoácidos , Brassica/metabolismo , Flores/genética , Flores/metabolismo , Filogenia , Proteínas de Plantas/classificação , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Ligação Proteica , Proteínas Quinases/metabolismo , Homologia de Sequência de Aminoácidos
16.
Org Biomol Chem ; 16(25): 4628-4632, 2018 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-29901667

RESUMO

In this study, a single fluorescent probe (DPFP) containing a 1,8-naphthalimide dye and a homoallylamino group for imaging pH and formaldehyde (FA) has been developed that exhibits significant blue fluorescence (λem at 455 nm) under acidic pH conditions (pH < 7.0) and green fluorescence (λem at 555 nm) in the presence of FA, respectively. Furthermore, probe DPFP was successfully applied to image acidic lysosomes and exogenous or endogenous FA in living HeLa cells.

17.
Acta Biochim Biophys Sin (Shanghai) ; 48(9): 777-87, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27590064

RESUMO

Self-incompatibility (SI) is an important mating system to prevent inbreeding and promote outcrossing. ARC1 and Exo70A1 function as the downstream targets of the S-locus receptor kinase and play conservative roles in Brassica SI signaling. Based on the sequence homology, Exo70A1 is divided into four subdomains: leucine zipper (Leu(128)-Leu(149)), hypervariable region (Ser(172)-Leu(197)), SUMO modification motif (Glu(260)-Ile(275)), and pfamExo70 domain (His(271)-Phe(627)). ARC1 contains four domains as follows: leucine zipper (Leu(116)-Leu(137)), coiled-coil domain (Thr(210)-Val(236)), U-box (Asp(282)-Trp(347)) motif, and ARM (Ala(415)-Thr(611)) domain. Bioinformatics analysis, yeast two-hybrid screening and pull-down assays show that leucine zipper and coiled-coil motifs of ARC1116-236 are required for the interaction with Exo70A1, while the addition of ARM motif results in loss of the interaction with Exo70A1. Meanwhile, the N-terminal of Exo70A1 without any domains shows a weak interaction with ARC1, and the level of LacZ expression increases with addition of leucine zipper and reaches the maximum value with hypervariable region and SUMO modification motif, indicating that hypervariable region and SUMO modification motif of Exo70A1172-275 is mainly responsible for the binding with ARC1, whereas pfamExo70 domain has little affinity for ARC1. Lys(181) located in the Exo70A1 hypervariable region may be the ubiquitination site mediating the interaction between ARC1 and Exo70A1. Therefore, both the leucine zipper with coiled-coil structure of ARC1116-236, and the hypervariable region and SUMO modification motif of Exo70A1172-275 are the core interaction domains between ARC1 and Exo70A1. Any factors affecting these core domains would be the regulators of ARC1 mediating ubiquitin degradation in self-incompatible system.


Assuntos
Brassica/genética , Proteínas de Plantas/química , Proteínas de Plantas/genética , Autoincompatibilidade em Angiospermas/genética , Sequência de Aminoácidos , Sítios de Ligação , Brassica/metabolismo , Modelos Moleculares , Proteínas de Plantas/metabolismo , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Homologia de Sequência de Aminoácidos , Transdução Genética , Técnicas do Sistema de Duplo-Híbrido , Proteínas de Transporte Vesicular/química , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
18.
Acta Biochim Biophys Sin (Shanghai) ; 47(5): 335-41, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25757952

RESUMO

Candida albicans is a major fungal pathogen of humans. The most striking biological feature of C. albicans is its phenotypic plasticity, allowing it to undergo morphological transitions in response to various environmental cues. Transcription factors play critical roles in the regulation of morphological transitions. Here, we report the role of opaque and filamentation inducer 1 (Ofi1), a previously uncharacterized zinc-finger-containing protein encoded by the gene orf19.4972, in the regulation of white-opaque switching and filamentous growth. Over-expression of OFI1 not only induced white-to-opaque switching but also promoted filamentation and invasive growth in C. albicans. Deletion of OFI1 had no obvious effect on filamentation under the culture conditions tested, while deletion of OFI1 reduced the frequency of white-to-opaque switching. We propose that Ofi1 functions downstream of Wor1, the master regulator of white-opaque switching. However, over-expression of OFI1 in the wor1/wor1 mutant could not induce the opaque phenotype, suggesting that Ofi1 does not work alone and other transcription factors downstream of Wor1 are also involved in this regulation. Given the importance of Ofi1 in the regulation of white-opaque switching and filamentation, the present study establishes a new link between these two processes.


Assuntos
Candida albicans/metabolismo , Fatores de Transcrição/metabolismo , Dedos de Zinco , Deleção de Genes , Fatores de Transcrição/genética
19.
Wei Sheng Wu Xue Bao ; 55(5): 579-86, 2015 May 04.
Artigo em Chinês | MEDLINE | ID: mdl-26259482

RESUMO

OBJECTIVE: To determine the function of high-affinity iron permeases, Ftr1 and Ftr2, we studied cell growth and filamentation ability of the ftr1/ftr1, ftr2/ftr2, and ftr1/ftr1 ftr2/ftr2 mutants under different culture conditions. METHODS: Cells of the wild type and mutants were cultured on different solid media at different temperatures. Cell growth and filamentation were observed. RESULTS: Deletion of either one of the FTR genes had no effect on the growth under all conditions tested. Deletion of both FTR1 and FTR2 led to obvious growth defect on Spider media, although addition of FeCl3 restored their growth. The double mutant also grew much more slowly on nutrients-limited synthetic media such as Lee's glucose and Lee's GlcNAc (N-acetylglucosamine). Moreover, deletion of FTR1 enhanced filamentation, whereas deletion of FTR2 weakened this ability. Deletion of both FTR1 and FTR2 recovered the ability of filamentation. CONCLUSION: Ftr1 and Ftr2 are very important for C. albicans growth under iron-limited condition and may participate in the utilization of some carbon sources including GlcNAc, ethnol, and glycerol. Ftr1 plays a negative, whereas Ftr2 plays a positive role in the regulation of filamentation in C. albicans.


Assuntos
Candida albicans/enzimologia , Candida albicans/crescimento & desenvolvimento , Proteínas Fúngicas/metabolismo , Hifas/crescimento & desenvolvimento , Ferro/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Candida albicans/genética , Candida albicans/metabolismo , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Hifas/enzimologia , Hifas/genética , Proteínas de Membrana Transportadoras/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA