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The Burkholderia cepacia complex (Bcc) consists of opportunistic pathogens known to cause pneumonia in immunocompromised individuals, especially those with cystic fibrosis. Treating Bcc pneumonia is challenging due to the pathogens' high multidrug resistance. Therefore, inhalation therapy with tobramycin powder, which can achieve high antibiotic concentrations in the lungs, is a promising treatment option. In this study, we investigated potential mechanisms that could compromise the effectiveness of tobramycin therapy. By selecting for Burkholderia cenocepacia survivors against tobramycin, we identified three spontaneous mutations that disrupt a gene encoding a key enzyme in the biosynthesis of cobalamin (Vitamin B12). This disruption may affect the production of succinyl-CoA by methylmalonyl-CoA mutase, which requires adenosylcobalamin as a cofactor. The depletion of cellular succinyl-CoA may impact the tricarboxylic acid (TCA) cycle, which becomes metabolically overloaded upon exposure to tobramycin. Consequently, the mutants exhibited significantly reduced reactive oxygen species (ROS) production. Both the wild-type and mutants showed tolerance to tobramycin and various other bactericidal antibiotics under microaerobic conditions. This suggests that compromised ROS-mediated killing, due to the impacted TCA cycle, underlies the mutants' tolerance to bactericidal antibiotics. The importance of ROS-mediated killing and the potential emergence of mutants that evade it through the depletion of cobalamin (Vitamin B12) provide valuable insights for developing strategies to enhance antibiotic treatments of Bcc pneumonia.
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Two blue-emitting materials, 4-(12-([1,1':3',1â³-terphenyl]-5'-yl)chrysen-6-yl)-N,N-diphenylaniline (TPA-C-TP) and 6-([1,1':3',1â³-terphenyl]-5'-yl)-12-(4-(1,2,2-triphenylvinyl)phenyl)chrysene (TPE-C-TP), were prepared with the composition of a chrysene core moiety and terphenyl (TP), triphenyl amine (TPA), and tetraphenylethylene (TPE) moieties as side groups. The maximum photoluminescence (PL) emission wavelengths of TPA-C-TP and TPE-C-TP were 435 and 369 nm in the solution state and 444 and 471 nm in the film state. TPA-C-TP effectively prevented intermolecular packing through the introduction of TPA, a bulky aromatic amine group, and it showed an excellent photoluminescence quantum yield (PLQY) of 86% in the film state. TPE-C-TP exhibited aggregation-induced emission; the PLQY increased dramatically from 0.1% to 78% from the solution state to the film state. The two synthesized materials had excellent thermal stability, with a high decomposition temperature exceeding 460 °C. The two compounds were used as emitting layers in a non-doped device. The TPA-C-TP device achieved excellent electroluminescence (EL) performance, with Commission Internationale de L'Eclairage co-ordinates of (0.15, 0.07) and an external quantum efficiency of 4.13%, corresponding to an EL peak wavelength of 439 nm.
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A novel quinophthalone derivative, 4,5,6,7-tetrachloro-2-(2-(3-hydroxy-1-oxo-1H-cyclopenta[b]naphthalen-2-yl)quinolin-4-yl)isoindoline-1,3-dione (TCHCQ), was designed and synthesized as a yellow colorant additive for green color filters in image sensors. The characteristics of the new material were evaluated in terms of optical, thermal, and chemical properties under solution and color filter film conditions. TCHCQ exhibited a significantly enhanced molar extinction coefficient in solution, being 1.21 times higher than that of the commercially used yellow colorant Y138. It also demonstrated excellent thermal stability, with a decomposition temperature (Td) exceeding 450 °C. Utilizing the nano-pigmentation process, TCHCQ was used to prepare nano-sized particles with an excellent average size of 35 nm. This enabled the fabrication of a color filter film with outstanding properties. The optical properties of the produced film revealed outstanding yellow colorant transmittance of 0.97% at 435 nm and 91.2% at 530 nm. The color filter film exhibited similar optical and thermal stability to Y138, with an improved chemical stability, as evidenced by a ΔEab value of 0.52. The newly synthesized TCHCQ is considered a promising candidate for use as a yellow colorant additive in image sensor color filters, demonstrating superior optical, thermal, and chemical stability.
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Three new blue materials, TPI-InCz, PAI-InCz, and CN-PAI-InCz, have been developed. In the film state, TPI-InCz and PAI-InCz exhibited emission peaks at 411 and 431 nm indicating deep blue emission. CN-PAI-InCz showed a peak emission at 452 nm, within the real blue region. When these three materials were used as the emissive layer to fabricate non-doped devices, CN-PAI-InCz showed the highest current efficiency of 2.91 cd A-1, power efficiency of 1.93 lm W-1, and external quantum efficiency of 3.31%. Among the synthesized materials, CN-PAI-InCz exhibited superior charge balance due to the introduction of CN groups, as confirmed by hole-only devices and electron-only devices. PAI-InCz demonstrated fast hole mobility with a value of 1.50 × 10-3 cm2 V-1 s-1, attributed to its planar and highly rigid structure. In the resulting devices, the Commission Internationale de l'Eclairage coordinates for TPI-InCz, PAI-InCz, and CN-PAI-InCz were (0.162, 0.048), (0.0161, 0.067), and (0.155, 0.099), all indicating emission in the blue region.
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This study proposes the use of physical unclonable functions employing circularly polarized light emission (CPLE) from nematic liquid crystal (NLC) ordering directed by helical nanofilaments in a mixed system composed of a calamitic NLC mixture and a bent-core molecule. To achieve this, an intrinsically nonemissive NLC is blended with a high concentration of a luminescent rod-like dye, which is miscible up to 10 wt % in the calamitic NLC without a significant decrease in the degree of alignment. The luminescence dissymmetry factor of CPLEs in the mixed system strongly depends on the degree of alignment of the dye-doped NLCs. Furthermore, the mixed system prepared in this study exhibits two randomly generated chiral domains with CPLEs of opposite signs. These chiral domains are characterized not only by their CPLE performances but also by their ability to generate random patterns up to several millimeters, making them promising candidates for high-performance secure authentication applications.
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In this study, we introduced the weak electron-accepting oxazole derivative 4,5-diphenyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazole (TPO) into both anthracene and pyrene moieties of a dual core structure. Ultimately, we developed 2-(4-(6-(anthracen-9-yl)pyren-1-yl)phenyl)-4,5-diphenyloxazole (AP-TPO) as the substitution on the second core, pyrene, and 4,5-diphenyl-2-(4-(10-(pyren-1-yl)anthracen-9-yl)phenyl)oxazole (TPO-AP) as the substitution on the first core, anthracene. Both materials exhibited maximum photoluminescence wavelengths at 433 and 443 nm in solution and emitted deep blue light with high photoluminescence quantum yields of 82% and 88%, respectively. When used as the emitting layer in non-doped devices, TPO-AP outperformed AP-TPO, achieving a current efficiency of 5.49 cd/A and an external quantum efficiency of 4.26% in electroluminescence. These materials introduce a new category of deep blue emitters in the organic light-emitting diodes field, combining characteristics related to the electron transport layer.
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We synthesized zinc oxide nanoparticles (ZnO NPs) by meticulously controlling both temperature and reaction times, allowing us to fine-tune their crystalline properties, morphology, and particle dimensions. This analysis confirmed the existence of a mixture of rod and sphere shapes (ZnO-I), including rod-shaped NPs with an average size of 14.8 nm × 5.2 nm and spherical NPs with an average diameter of 5.27 nm. We subsequently incorporated these synthesized ZnO NPs into organic light-emitting diode (OLED) devices for red, green, and blue colors, utilizing them as the electron injection layer through a solution-based process. The green OLED device using ZnO-I exhibited a promising current efficiency of 4.02 cd/A and an external quantum efficiency of 1.47%.
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We report three highly efficient multiresonance thermally activated delayed fluorescence blue-emitter host materials that include 5,9-dioxa-13b-boranaphtho[3,2,1-de]anthracene (DOBNA) and tetraphenylsilyl groups. The host materials doped with the conventional N7,N7,N13,N13,5,9,11,15-octaphenyl-5,9,11,15-tetrahydro-5,9,11,15-tetraaza-19b,20b-diboradinaphtho[3,2,1-de:1',2',3'-jk]pentacene-7,13-diamine (ν-DABNA) blue emitter exhibit a high photoluminescence quantum yield greater than 0.82, a high horizontal orientation greater than 88%, and a short photoluminescence decay time of 0.96-1.93 µs. Among devices fabricated using six synthesized compounds, the device with (4-(2,12-di-tert-butyl-5,9-dioxa-13b-boranaphtho[3,2,1-de]anthracen-7-yl)phenyl)triphenylsilane (TDBA-Si) shows high external quantum efficiency values of 36.2/35.0/31.3% at maximum luminance/500 cd m-2/1,000 cd m-2. This high performance is attributed to fast energy transfer from the host to the dopant. Other factors possibly contributing to the high performance are a T1 excited-state contribution, inhibition of aggregation by the bulky tetraphenylsilyl groups, high horizontal orientation, and high thermal stability. We achieve a high efficiency greater than 30% and a small roll-off value of 4.9% at 1,000 cd m-2 using the TDBA-Si host material.
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Ubiquitin-specific protease 2 (USP2) is a deubiquitinase belonging to the USPs subfamily. USP2 has been known to display various biological effects including tumorigenesis and inflammation. Therefore, we aimed to examine the sensitization effect of USP2 in TRAIL-mediated apoptosis. The pharmacological inhibitor (ML364) and siRNA targeting USP2 enhanced TNF-related apoptosis-inducing ligand (TRAIL)-induced cancer cell death, but not normal cells. Mechanistically, USP2 interacted with survivin, and ML364 degraded survivin protein expression by increasing the ubiquitination of survivin. Overexpression of survivin or USP2 significantly prevented apoptosis through cotreatment with ML364 and TRAIL, whereas a knockdown of USP2 increased sensitivity to TRAIL. Taken together, our data suggested that ML364 ubiquitylates and degrades survivin, thereby increasing the reactivity to TRAIL-mediated apoptosis in cancer cells.
Asunto(s)
Neoplasias , Ligando Inductor de Apoptosis Relacionado con TNF , Humanos , Regulación hacia Abajo , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Survivin/genética , Muerte Celular , Neoplasias/genética , Ubiquitina Tiolesterasa/genéticaRESUMEN
The anti-proliferative effects of a newly developed N3-acyl-N5-aryl-3,5-diaminoindazole analog, KMU-191, have been previously evaluated in various cancer cells. However, the detailed anti-cancer molecular mechanisms of KMU-191 remain unknown. In this study, we investigated anti-cancer mechanisms by which KMU-191 regulates apoptosis-related genes in human clear cell renal cell carcinoma Caki cells. KMU-191 induced poly ADP-ribose polymerase cleavage and caspase-dependent apoptosis. In addition, KMU-191 induced down-regulation of the long form of cellular FADD-like IL-1ß-converting enzyme inhibitory protein (c-FLIP (L)) at the transcriptional level as well as that of long form of myeloid cell leukemia (Mcl-1 (L)) and B-cell lymphoma-extra large at the post-transcriptional level. Furthermore, KMU-191-induced apoptosis was closely associated with the Mcl-1 (L) down-regulation, but also partially associated with c-FLIP (L) down-regulation. In contrast, KMU-191 up-regulated p53, which is closely related to KMU-191-induced apoptosis. Although KMU-191 showed cytotoxicity of normal cells, it unusually did not induce cardiotoxicity. Taken together, these results suggest that a multi-target small molecule, N3-acyl-N5-aryl-3,5-diaminoindazole analog, KMU-191 is a potential anti-cancer agent that does not induce cardiotoxicity.
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Two new deep-blue emitters with bipolar properties based on an organoboron acceptor and carbazole donor were newly synthesized: 2-(9H-carbazol-9-yl)-5-(2,12-di-tert-butyl-5,9-dioxa-13b-boranaphtho [3,2,1-de]anthracen-7-yl)-5H-benzo[b]carbazole (TDBA-BCZ) and 5-(2,12-di-tert-butyl-5,9-dioxa-13b-boranaphtho [3,2,1-de]anthracen-7-yl)-8-phenyl-5,8-dihydroindolo[2,3-c]carbazole (TDBA-PCZ). The two emitters showed deep-blue and real-blue photoluminescence emission in their solution and film states, respectively. The doped spin-coated films were prepared using synthesized materials and showed a root-mean-square roughness of less than 0.52 nm, indicating excellent surface morphology. The doped devices, fabricated via a solution process using TDBA-BCZ and TDBA-PCZ as the dopants, showed electroluminescence peaks at 428 and 461 nm, corresponding to the Commission Internationale de L'éclairage (CIE) coordinates of (0.161, 0.046) and (0.151, 0.155), respectively. The external quantum efficiency (EQE)/current efficiency (CE) of the solution-processed forward devices, with TDBA-BCZ and TDBA-PCZ as dopants, were 7.73%/8.67 cd/A and 10.58%/14.24 cd/A, respectively. An inverted OLED device fabricated using rod-shaped ZnO nanoparticles as an electron injection layer showed a CE of 1.09 cd/A and an EQE of 0.30%.
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Novel yellow azo pyridone dye derivatives were synthesized for use in image-sensor color filters. The synthesized compounds have a basic chemical structure composed of azo, hydroxy, amide, and nitrile groups as well as different halide groups. New materials were evaluated on the basis of their optical, thermal, and surface properties under conditions mimicking those of a commercial device fabrication process. A comparison of their related performance revealed that, among the four prepared compounds, 5-((4,6-dichlorocyclohexa-2,4-dien-1-yl)diazenyl)-6-hydroxy-1,4-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (Cl-PAMOPC) exhibited the best performance as an image-sensor color filter material, including a solubility greater than 0.1 wt% in propylene glycol monomethyl ether acetate solvent, a high decomposition temperature of 263 °C, and stable color difference values of 4.93 and 3.88 after a thermal treatment and a solvent-resistance test, respectively. The results suggest that Cl-PAMOPC can be used as a green dye additive in an image-sensor colorant.
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Dihidropiridinas , Compuestos Inorgánicos , Acetatos , Amidas , Compuestos Azo/química , Color , Colorantes/química , Nitrilos , Piridonas , SolventesRESUMEN
The nano-biocomposite electrodes composed of carbon nanotube (CNT), polypyrrole (PPy), and E. coli-bacteria were investigated for electrochemical supercapacitors. For this purpose, PPy/CNT-E. coli was successfully synthesized through oxidative polymerization. The PPy/CNT-E. coli electrode exhibited a high specific capacitance of 173 Fâg-1 at the current density of 0.2 Aâg-1, which is much higher than that (37 Fâg-1) of CNT. Furthermore, it displayed sufficient stability after 1000 charge/discharge cycles. The CNT, PPy/CNT, and PPy/CNT-E. coli composites were characterized by x-ray diffraction, scanning electron microscopy, and surface analyzer (Brunauer-Emmett-Teller, BET). In particular, the pyrrole monomers were easily adsorbed and polymerized on the surface of CNT materials, as well as E. coli bacteria enhanced the surface area and porous structure of the PPy/CNT-E. coli composite electrode resulting in high performance of devices.
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Ubiquitin-specific protease 1 (USP1) is a deubiquitinase involved in DNA damage repair by modulating the ubiquitination of major regulators, such as PCNA and FANCD2. Because USP1 is highly expressed in many cancers, dysregulation of USP1 contributes to cancer therapy. However, the role of USP1 and the mechanisms underlying chemotherapy remain unclear. In this study, we found high USP1 expression in tumor tissues and that it correlated with poor prognosis in RCC. Mechanistically, USP1 enhanced survivin stabilization by removing ubiquitin. Pharmacological inhibitors (ML23 and pimozide) and siRNA targeting USP1 induced downregulation of survivin expression. In addition, ML323 upregulated DR5 expression by decreasing miR-216a-5p expression at the post-transcriptional level, and miR-216a-5p mimics suppressed the upregulation of DR5 by ML323. Inhibition of USP1 sensitized cancer cells. Overexpression of survivin or knockdown of DR5 markedly prevented the co-treatment with ML323 and TRAIL-induced apoptosis. These results of in vitro were proved in a mouse xenograft model, in which combined treatment significantly reduced tumor size and induced survivin downregulation and DR5 upregulation. Furthermore, USP1 and survivin protein expression showed a positive correlation, whereas miR-216a-5p and DR5 were inversely correlated in RCC tumor tissues. Taken together, our results suggest two target substrates of USP1 and demonstrate the involvement of survivin and DR5 in USP1-targeted chemotherapy.
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Antineoplásicos , Carcinoma de Células Renales , Neoplasias Renales , MicroARNs , Proteasas Ubiquitina-Específicas , Animales , Antineoplásicos/farmacología , Apoptosis/genética , Carcinoma de Células Renales/metabolismo , Línea Celular Tumoral , Enzimas Desubicuitinizantes/genética , Regulación hacia Abajo/genética , Humanos , Ratones , MicroARNs/metabolismo , Pimozida/farmacología , Antígeno Nuclear de Célula en Proliferación/metabolismo , ARN Interferente Pequeño/farmacología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF , Survivin/genética , Survivin/metabolismo , Proteasas Ubiquitina-Específicas/antagonistas & inhibidores , Proteasas Ubiquitina-Específicas/genética , Ubiquitinas/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
All-inorganic halide perovskite nanocrystals are next-generation materials with excellent optical and semiconductor properties suitable for display applications. In this study, we introduce an optimized ultrasonication method for the high-capacity synthesis of highly luminescent inorganic perovskite nanocrystals. After the synthesis of CsPbBr3 with superior optical performance by ultrasonication method, halide anion exchange was performed to tune the stable emission wavelength over the entire visible range. In particular, the maximum photoluminescence wavelengths of the red and green perovskite nanocrystals were appropriate for light-emitting diode applications, and their full-width-at-half-maximum were very narrow, showing outstanding color purity. The materials also had excellent thermal and photo-stability, which is a necessary requirement for perovskite nanocrystal/organic light-emitting diode hybrid device applications. We formulated uniformly stable perovskite nanocrystal inks and optimized their physical and rheological properties for successful inkjet-printing. Finally, we fabricated a hybrid device with a color conversion layer based on the red and green perovskite nanocrystals synthesized using the optimized ultrasonication and halide-ion-exchange methods. The color reproduction range of the fabricated devices was 27.3 % wider than that of the National Television System Committee values, indicating very vivid colors.
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ß-Lactamase production facilitates bacterial survival in nature and affects many infection therapies. However, much of its regulation remains unexplored. We used a genetics-based approach to identify a two-component system (TCS) present in a strain of Burkholderia thailandensis essential for the regulated expression of a class A ß-lactamase gene, penL, by sensing subtle envelope disturbance caused by ß-lactams, polymyxin B, or other chemical agents. The genes encoding stress responses and resistance to various antibiotics were coregulated, as were the catabolic genes that enabled the B. thailandensis strain to grow on penicillin G or phenylacetate, a degradation product of penicillin G. This regulon has likely evolved to facilitate bacterial survival in the soil microbiome that contains a multitude of antibiotic producers. Practically, this regulatory system makes this TCS, which we named BesRS, an excellent drug target for the purpose of increasing antibiotic efficacy in combination therapies for Burkholderia infections. IMPORTANCE ß-lactam antibiotics are the most frequently used drugs to treat infectious diseases. Although the production of ß-lactamases by bacteria is the main cause of treatments being compromised, much of the gene regulation mechanism governing the levels of these enzymes has not been fully explored. In this study, we report a novel ß-lactamase gene regulation mechanism that is governed by a two-component system responding to disturbances in the cell envelope. We showed gene regulation is a part of a regulon that includes genes involved in stress responses, resistance to various antibiotics, and a catabolic pathway for ß-lactams. This regulon may have been evolved to facilitate bacterial survival in the soil niches, which are highly competitive environments because of the presence of various antibiotic-producing microbes. The discovery of the ß-lactamase gene regulation mechanism opens new avenues for developing therapeutic strategies in the fight against antibiotic resistance.
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Regulón , beta-Lactamasas , Antibacterianos/farmacología , Suelo , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , beta-Lactamas/farmacologíaRESUMEN
Three organic blue-light-emitting tetraphenylethylene (TPE) derivatives that exhibit aggregation-induced emission (AIE) were used as additives in the preparation of inorganic perovskite-structured green-light-emitting materials for three-color white-light emission. For these organic-inorganic light-emitting materials, two-color (blue and green) light-emitting films based on the CsPbBr3 perovskite-structured green-light-emitting inorganic material were prepared. The three TPE derivatives were prepared by varying the number of bromide groups, and a distinct AIE effect was confirmed when the derivatives were dissolved in a water-tetrahydrofuran mixed solvent containing 90 vol% water. When 0.2 molar ratio of the 1,1,2,2-tetrakis(4-bromophenyl)ethylene (TeBrTPE) additive was mixed with nanocrystal-pinning toluene solvent, the green-light-emission photoluminescence quantum efficiency (PLQY) value at 535 nm was 47 times greater than that of the pure bulk CsPbBr3 without additives and a blue emission at 475 nm was observed from the TeBrTPE itself. When a CBP:Ir(piq)3 film was prepared on top of this layer, three PL peaks with maximum wavelength values of 470, 535, and 613 nm were confirmed. The film exhibited white-light emission with CIE color coordinates of (0.25, 0.36).
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The development of rigid polyaromatic building blocks for narrowband violet fluorophores has received tremendous attention. Herein, we designed and synthesized two new triangle-shaped rigid building blocks, namely, 2,5-di-tert-butylindolo[3,2,1-jk]carbazole (tBuICz) and 2,11-di-tert-butylindolo[3,2,1-jk]carbazole-4-carbonitrile (tBuICzCN), and tethered them with different chromophores to yield a series of violet-blue fluorophores, viz., ICzTPA-ICzPICN, and studied their structure-function relationship. The appended chromophores and cyano unit played a vital role in controlling the optical and electrical properties of the compounds. Except triphenylamine-substituted derivatives, the compounds showed pure violet emission (λem ≤ 403 nm). Intriguingly, the compounds exhibited narrow-band emission with a full-width at half-maximum ≤ 40 nm, attributed to the rigidity of the ICz core. The emission of the compounds displayed positive solvatochromism, which is ascribed to the photoinduced intramolecular charge transfer in the excited state. The compounds revealed excellent thermal robustness with T5d ≥ 363 °C. The triphenylamine-featuring derivatives displayed a high-lying HOMO compared to their congeners due to their electron-rich nature. When we applied these materials in organic light-emitting diodes, ICzPI outperformed in the series with an EQEmax of 3.07% and a current efficiency of 1.04 cd/A. Notably, its CIEy â¼ 0.046 precisely matched with the Rec.2020 standard of deep-blue color (CIEy â¼ 0.046).
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Conventional fluorescent dyes have the property of decreasing fluorescence due to aggregation-caused quenching effects at high concentrations, whereas aggregation-induced emission dyes have the property of increasing fluorescence as they aggregate with each other. In this study, diketopyrrolopyrrole-based long-wavelength aggregation-induced emission dyes were used to prepare biocompatible nanoparticles suitable for bioimaging. Aggregation-induced emission nanoparticles with the best morphology and photoluminescence intensity were obtained through a fast, simple preparation method using an ultrasonicator. The optimally prepared nanoparticles from 3,6-bis(4-((E)-4-(bis(40-(1,2,2-triphenylvinyl)-[1,10-biphenyl]-4-yl)amino)styryl)phenyl)-2,5-dihexyl-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione (DP-R2) with two functional groups having aggregation-induced emission properties and additional donating groups at the end of the triphenylamine groups were considered to have the greatest potential as a fluorescent probe for bioimaging. Furthermore, it was found that the tendency for aggregation-induced emission, which was apparent for the dye itself, became much more marked after the dyes were incorporated within nanoparticles. While the photoluminescence intensities of the dyes were observed to decrease rapidly over time, the prepared nanoparticles encapsulated within the biocompatible polymers maintained their initial optical properties very well. Lastly, when the cell viability test was conducted, excellent biocompatibility was demonstrated for each of the prepared nanoparticles.
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Nanopartículas , Colorantes Fluorescentes , Cetonas , PirrolesRESUMEN
Cathepsin K is highly expressed in various types of cancers. However, the effect of cathepsin K inhibition in cancer cells is not well characterized. Here, cathepsin K inhibitor (odanacatib; ODN) and knockdown of cathepsin K (siRNA) enhanced oxaliplatin-induced apoptosis in multiple cancer cells through Bax upregulation. Bax knockdown significantly inhibited the combined ODN and oxaliplatin treatment-induced apoptotic cell death. Stabilization of p53 by ODN played a critical role in upregulating Bax expression at the transcriptional level. Casein kinase 2 (CK2)-dependent phosphorylation of OTUB1 at Ser16 played a critical role in ODN- and cathepsin K siRNA-mediated p53 stabilization. Interestingly, ODN-induced p53 and Bax upregulation were modulated by the production of mitochondrial reactive oxygen species (ROS). Mitochondrial ROS scavengers prevented OTUB1-mediated p53 stabilization and Bax upregulation by ODN. These in vitro results were confirmed by in mouse xenograft model, combined treatment with ODN and oxaliplatin significantly reduced tumor size and induced Bax upregulation. Furthermore, human renal clear carcinoma (RCC) tissues revealed a strong correlation between phosphorylation of OTUB1(Ser16) and p53/Bax expression. Our results demonstrate that cathepsin K inhibition enhances oxaliplatin-induced apoptosis by increasing OTUB1 phosphorylation via CK2 activation, thereby promoting p53 stabilization, and hence upregulating Bax.