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1.
Nanomicro Lett ; 16(1): 178, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38656466

RESUMEN

This study presents experimental evidence of the dependence of non-radiative recombination processes on the electron-phonon coupling of perovskite in perovskite solar cells (PSCs). Via A-site cation engineering, a weaker electron-phonon coupling in perovskite has been achieved by introducing the structurally soft cyclohexane methylamine (CMA+) cation, which could serve as a damper to alleviate the mechanical stress caused by lattice oscillations, compared to the rigid phenethyl methylamine (PEA+) analog. It demonstrates a significantly lower non-radiative recombination rate, even though the two types of bulky cations have similar chemical passivation effects on perovskite, which might be explained by the suppressed carrier capture process and improved lattice geometry relaxation. The resulting PSCs achieve an exceptional power conversion efficiency (PCE) of 25.5% with a record-high open-circuit voltage (VOC) of 1.20 V for narrow bandgap perovskite (FAPbI3). The established correlations between electron-phonon coupling and non-radiative decay provide design and screening criteria for more effective passivators for highly efficient PSCs approaching the Shockley-Queisser limit.

2.
Int J Biol Sci ; 20(6): 2297-2309, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38617545

RESUMEN

Background: Tyrosine kinase with immunoglobulin and EGF-like domains 1 (TIE1) is known as an orphan receptor prominently expressed in endothelial cells and participates in angiogenesis by regulating TIE2 activity. Our previous study demonstrated elevated TIE1 expression in cervical cancer cells. However, the role of TIE1 in cervical cancer progression, metastasis and treatment remains elusive. Methods: Immunohistochemistry staining for TIE1 and Basigin was performed in 135 human cervical cancer tissues. Overexpressing vectors and siRNAs were used to manipulate gene expression in tumor cells. Colony formation, wound healing, and transwell assays were used to assess cervical cancer cell proliferation and migration in vitro. Subcutaneous xenograft tumor and lung metastasis mouse models were established to examine tumor growth and metastasis. Co-Immunoprecipitation and Mass Spectrometry were applied to explore the proteins binding to TIE1. Immunoprecipitation and immunofluorescence staining were used to verify the interaction between TIE1 and Basigin. Cycloheximide chase assay and MG132 treatment were conducted to analyze protein stability. Results: High TIE1 expression was associated with poor survival in cervical cancer patients. TIE1 overexpression promoted the proliferation, migration and invasion of cervical cancer cells in vitro, as well as tumor growth and metastasis in vivo. In addition, Basigin, a transmembrane glycoprotein, was identified as a TIE1 binding protein, suggesting a pivotal role in matrix metalloproteinase regulation, angiogenesis, cell adhesion, and immune responses. Knockdown of Basigin or treatment with the Basigin inhibitor AC-73 reversed the tumor-promoting effect of TIE1 in vitro and in vivo. Furthermore, we found that TIE1 was able to interact with and stabilize the Basigin protein and stimulate the Basigin-matrix metalloproteinase axis. Conclusion: TIE1 expression in cervical cells exerts a tumor-promoting effect, which is at least in part dependent on its interaction with Basigin. These findings have revealed a TIE2-independent mechanism of TIE1, which may provide a new biomarker for cervical cancer progression, and a potential therapeutic target for the treatment of cervical cancer patients.


Asunto(s)
Neoplasias Pulmonares , Neoplasias del Cuello Uterino , Animales , Femenino , Humanos , Ratones , Basigina , Adhesión Celular , Células Endoteliales , Neoplasias del Cuello Uterino/genética
3.
Parasite ; 31: 12, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38450718

RESUMEN

Blastocystis sp., a significant zoonotic parasite with a global distribution, was the focus of this study, which aimed to investigate its prevalence and genetic diversity among diarrheic and asymptomatic children in Wenzhou, China. We collected 1,032 fecal samples from Yuying Children's Hospital, Wenzhou, China, comprising 684 from children with diarrhea and 348 from asymptomatic children. Genomic DNA extracted from these samples was used to detect Blastocystis spp. by PCR, targeting the small subunit ribosomal RNA gene. Subsequently, a phylogenetic tree was constructed, applying the maximum likelihood method. Blastocystis spp. were detected in 67 (6.5%) of the fecal samples. The prevalence rate of Blastocystis spp. in diarrheic children (8.8%; 60/684) was significantly higher than that in asymptomatic children (2.0%; 7/348) (χ 2 = 17.3, p < 0.001). Sequence analysis of the SSU rRNA gene identified five known Blastocystis spp. subtypes, ST1 (n = 12), ST2 (n = 5), ST3 (n = 35), ST4 (n = 12), and ST7 (n = 3). ST1 and ST3 were present in both diarrheic and asymptomatic children, while ST2, ST4, and ST7 were exclusive to diarrheic children. Intra-subtype genetic polymorphisms were identified, comprising four variations in ST1 (ST1-1 to ST1-4), five in ST3 (ST3-1 to ST3-5), two in ST4 (ST4-1 and ST4-2), and two in ST7 (ST7-1 and ST7-2). Notably, ST1-2 to ST1-4, ST3-3 to ST3-5, and ST7-1 and ST7-2 represent newly identified variations. The composition and genetic characteristics of subtypes among children in this region suggest various sources of infection, including human-to-human and animal-to-human transmission.


Title: Prévalence moléculaire et distribution des sous-types de Blastocystis spp. parmi les enfants diarrhéiques et asymptomatiques à Wenzhou, Province du Zhejiang, Chine. Abstract: Blastocystis sp., un parasite zoonotique important avec une distribution mondiale, était au centre de cette étude, qui visait à étudier sa prévalence et sa diversité génétique parmi les enfants diarrhéiques et asymptomatiques de Wenzhou, en Chine. Nous avons collecté 1 032 échantillons fécaux à l'hôpital pour enfants Yuying de Wenzhou, en Chine, dont 684 provenant d'enfants souffrant de diarrhée et 348 d'enfants asymptomatiques. L'ADN génomique extrait de ces échantillons a été utilisé pour détecter Blastocystis sp. par PCR, ciblant le gène de la petite sous-unité de l'ARN ribosomal. Par la suite, un arbre phylogénétique a été construit, en appliquant la méthode du maximum de vraisemblance. Blastocystis sp. a été détecté dans 67 (6,5 %) des échantillons fécaux. Le taux de prévalence de Blastocystis spp. chez les enfants diarrhéiques (8,8 % ; 60 / 684) était significativement plus élevé que chez les enfants asymptomatiques (2,0 % ; 7 / 348) (χ2 = 17,3, p < 0,001). L'analyse de la séquence du gène de l'ARNr SSU a identifié cinq sous-types de Blastocystis spp., ST1 (n = 12), ST2 (n = 5), ST3 (n = 35), ST4 (n = 12) et ST7 (n = 3). Les sous-types ST1 et ST3 étaient présents chez les enfants diarrhéiques et asymptomatiques, tandis que ST2, ST4 et ST7 étaient exclusifs aux enfants diarrhéiques. Des polymorphismes génétiques intra-sous-types ont été identifiés, comprenant quatre variations dans ST1 (ST1-1 à ST1-4), cinq dans ST3 (ST3-1 à ST3-5), deux dans ST4 (ST4-1 et ST4-2) et deux dans ST7 (ST7-1 et ST7-2). Notamment, ST1-2 à ST1-4, ST3-3 à ST3-5, ST7-1 et ST7-2 représentent des variations nouvellement identifiées. La composition et les caractéristiques génétiques des sous-types chez les enfants de cette région suggèrent diverses sources d'infection, notamment la transmission interhumaine et animale.


Asunto(s)
Blastocystis , Proteína 1 Similar al Receptor de Interleucina-1 , Animales , Niño , Humanos , Filogenia , Prevalencia , China/epidemiología , Blastocystis/genética
4.
Angew Chem Int Ed Engl ; 63(14): e202316898, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38340024

RESUMEN

The main obstacles to promoting the commercialization of perovskite solar cells (PSCs) include their record power conversion efficiency (PCE), which still remains below the Shockley-Queisser limit, and poor long-term stability, attributable to crystallographic defects in perovskite films and open-circuit voltage (Voc) loss in devices. In this study, potassium (4-tert-butoxycarbonylpiperazin-1-yl) methyl trifluoroborate (PTFBK) was employed as a multifunctional additive to target and modulate bulk perovskite defects and carrier dynamics of PSCs. Apart from simultaneously passivating anionic and cationic defects, PTFBK could also optimize the energy-level alignment of devices and weaken the interaction between carriers and longitudinal optical phonons, resulting in a carrier lifetime of greater than 3 µs. Furthermore, it inhibited non-radiative recombination and improved the crystallization capacity in the target perovskite film. Hence, the target rigid and flexible p-i-n PSCs yielded champion PCEs of 24.99 % and 23.48 %, respectively. More importantly, due to hydrogen bonding between formamidinium and fluorine, the target devices exhibited remarkable thermal, humidity, and operational tracking at maximum power point stabilities. The reduced Young's modulus and residual stress in the perovskite layer also provided excellent bending stability for flexible target devices.

5.
Small ; : e2310742, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38329192

RESUMEN

Targeted treatment of the interface between electron transport layers (ETL) and perovskite layers is highly desirable for achieving passivating effects and suppressing carrier nonradiative recombination, leading to high performance and long-term stability in perovskite solar cells (PSCs). In this study, a series of non-fullerene acceptors (NFAs, Y-H, Y-F, and Y-Cl) are introduced to optimize the properties of the perovskite/ETL interface. This optimization involves passivating Pb2+ defects, releasing stress, and modulating carrier dynamics through interactions with the perovskite. Remarkably, after modifying with NFAs, the absorption range of perovskite films into the near-infrared region is extended. As expected, Y-F, with the largest electrostatic potential, facilitates the strongest interaction between the perovskite and its functional groups. Consequently, champion power conversion efficiencies of 21.17%, 22.21%, 23.25%, and 22.31% are achieved for control, Y-H-, Y-F-, and Y-Cl-based FA0.88 Cs0.12 PbI2.64 Br0.36 (FACs) devices, respectively. This treatment also enhances the heat stability and air stability of the corresponding devices. Additionally, these modifier layers are applied to enhance the efficiency of Cs0.05 (FA0.95 MA0.05 )0.95 PbI2.64 Br0.36 (FAMA) devices. Notably, a champion PCE exceeding 24% is achieved in the Y-F-based FAMA device. Therefore, this study provides a facile and effective approach to target the interface, thereby improving the efficiency and stability of PSCs.

6.
Commun Biol ; 7(1): 25, 2024 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-38182874

RESUMEN

Degradation of unliganded androgen receptor (AR) in prostate cancer cells can be prevented by proteasome inhibition, but this is associated with only modest increases in polyubiquitylated AR. An inhibitor (VLX1570) of the deubiquitylases associated with the proteasome did not increase ubiquitylation of unliganded AR, indicating that AR is not targeted by these deubiquitylases. We then identified a series of AR ubiquitylation sites, including a not previously identified site at K911, as well as methylation sites and previously identified phosphorylation sites. Mutagenesis of K911 increases AR stability, chromatin binding, and transcriptional activity. We further found that K313, a previously reported ubiquitylation site, could also be methylated and acetylated. Mutagenesis of K313, in combination with K318, increases AR transcriptional activity, indicating that distinct posttranslational modifications at K313 differentially regulate AR activity. Together these studies expand the spectrum of AR posttranslational modifications, and indicate that the K911 site may regulate AR turnover on chromatin.


Asunto(s)
Complejo de la Endopetidasa Proteasomal , Receptores Androgénicos , Masculino , Humanos , Receptores Androgénicos/genética , Ubiquitinación , Procesamiento Proteico-Postraduccional , Cromatina/genética
7.
Small ; : e2308877, 2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-37948431

RESUMEN

Tin halide perovskite solar cells (PSCs) are regarded as the most promising lead-free alternatives for photovoltaic applications. However, they still suffer from uncompetitive photovoltaic performance because of the facile Sn2+ oxidation and Sn-related defects. Herein, a defect and carrier management strategy by using diaminopyridine (DP) and 4-bromo-2,6-diaminopyridine (4BrDP) as multifunctional additives for tin halide perovskites is reported. Both DP and 4BrDP induced strong interaction with tin perovskites by coordinate bonding and N─H···I hydrogen bonding, which greatly suppresses the micro-strain and Urbach energy of tin halide perovskite films. The strong hydrogen bonding inhibits the formation of I3 - and related defect density. Meanwhile, the electron-donor species of halogen bond in 4BrDP provides higher reactivity of 2 and 6 sites, which indicates stronger passivation ability with tin halide perovskites. These advances enable a champion power conversion efficiency (PCE) of 13.40% in 4BrDP-processed devices with remarkable improvement in both open-circuit voltage (Voc ) of 881 mV and fill factor (FF) of 71.26%. The 4BrDP devices retain 91% and 82% of the pristine PCE after 2000 h storage in N2 atmosphere and 1000 h under 85 °C, respectively. Therefore, this work provides new insight into molecular design for high-performance and stable lead-free optoelectronics.

8.
Mater Horiz ; 10(11): 5223-5234, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37727103

RESUMEN

Perovskite films are susceptible to degradation during their service period due to their weak mechanical properties. Acylhydrazone-bonded waterborne polyurethane (Ab-WPU) was employed as dynamic covalent polymer engineering to develop self-healing perovskite solar cells (SHPSCs). Ab-WPU enhances the crystallinity of the perovskite film, passivates the defects of the perovskite film through functional groups, and demonstrates promising flexibility and mild temperature self-healing properties of SHPSCs. The champion efficiency of SHPSCs on rigid and flexible substrates reaches 24.2% and 21.27% respectively. The moisture and heat stability of devices were improved. After 1000 bending cycles, the Ab-WPU-modified flexible device can be restored to an efficiency of over 95% of its original efficiency by heating to 60 °C. This is because the dynamic acylhydrazone bond can be activated to repair perovskite film defects at a mild temperature of 60 °C as evidenced by in situ AFM studies. This strategy provides an effective pathway for dynamic self-healing materials in PSCs under operational conditions.

9.
Adv Mater ; 35(38): e2302752, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37308171

RESUMEN

The defects and phase segregation in perovskite will significantly reduce the performance and stability of perovskite solar cells (PSCs). In this work, a deformable coumarin is employed as a multifunctional additive for formamidinium-cesium (FA-Cs) perovskite. During the annealing process of perovskite, the partial decomposition of coumarin passivates the Pb2+ , iodine, and organic cation defects. Additionally, coumarin can affect colloidal size distributions, resulting in relatively large grain size and good crystallinity of target perovskite film. Hence, the carrier extraction/transport can be promoted, trap-assisted recombination is reduced, and energy levels are optimized in target perovskite films. Furthermore, the coumarin treatment can significantly release residual stress. As a result, the champion power conversion efficiencies (PCEs) of 23.18% and 24.14% are obtained for Br-rich (FA0.88 Cs0.12 PbI2.64 Br0.36 ) and Br-poor (FA0.96 Cs0.04 PbI2.8 Br0.12 ) based devices, respectively. The flexible PSCs based on Br-poor perovskite exhibit an excellent PCE of 23.13%, one of the highest values for flexible PSCs reported to date. Due to the inhibition of phase segregation, the target devices exhibit excellent thermal and light stability. This work provides new insights into the additive engineering of passivating defects, stress relief, and inhibition of phase segregation of perovskite films, offering a reliable method to develop state-of-the-art solar cells.

10.
Environ Pollut ; 316(Pt 2): 120550, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36328284

RESUMEN

Uranium extraction from radioactive nuclear waste is vital for sustainable energy supply and ecological security. Herein, a polyethyleneimine-chitosan composite microspheres n-PEI/ECH-CTS (n = 0.1, 0.2, 0.3, 0.4, 0.5) were synthetized for efficient and selective uranium adsorption. The prepared chitosan microspheres with uniform size, uniform dispersion and good mechanical strength combine cost-effectiveness and environmental benefits. The 0.4-PEI/ECH-CTS exhibits the highest adsorption capacity of 380.65 mg g-1 within only 4 h due to high nitrogen content of 6.57 mol kg-1. The DFT calculations confirms that the optimal coordination mode of UO22+ and 0.4-PEI/ECH-CTS is one UO22+ chelated with two -NH2 from two adsorption units, respectively. Adsorption efficiency of U(VI) from simulated nuclear wastewater achieves to 100%, and the Kd value is up to 1.1 × 104 mL g-1, which is 1.7 × 104-6.1 × 104 times that of coexisting ions. The CU(VI) reduces in simulated wastewater from 10.98 mg L-1 to 1 µg L-1, which is well below the US Environmental Protection Agency uranium limits for drinking water (30 µg L-1). Besides, 0.4-PEI/ECH-CTS still maintains above 95% adsorption efficiency after seven cycles. In short, the 0.4-PEI/ECH-CTS microspheres integrate high performance, practicality and cost-effectiveness, which has great advantages in practical industrial applications.


Asunto(s)
Quitosano , Residuos Radiactivos , Uranio , Polietileneimina , Aguas Residuales , Microesferas , Cinética , Adsorción , Concentración de Iones de Hidrógeno
11.
Angew Chem Int Ed Engl ; 62(8): e202217526, 2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-36581737

RESUMEN

Despite the great progress of flexible perovskite solar cells (f-PSCs), it still faces several challenges during the homogeneous fabrication of high-quality perovskite thin films, and overcoming the insufficient exciton dissociation. To the ends, we rationally design the ferroelectric two-dimensional (2D) perovskite based on pyridine heterocyclic ring as the organic interlayer. We uncover that incorporation of the ferroelectric 2D material into 3D perovskite induces an increased built-in electric field (BEF), which enhances the exciton dissociation efficiency in the device. Moreover, the 2D seeds could assist the 3D crystallization by forming more homogeneous and highly-oriented perovskite crystals. As a result, an impressive power conversion efficiency (PCE) over 23 % has been achieved by the f-PSCs with outstanding ambient stability. Moreover, the piezo/ferroelectric 2D perovskite intrigues a decreased hole transport barriers at the ITO/perovskite interface under tensile stress, which opens new possibilities for developing highly-efficient f-PSCs.

12.
J Phys Chem Lett ; 12(39): 9595-9601, 2021 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-34582202

RESUMEN

Lead is widely used as a crucial elemental for lead acid batteries (LABs) and emerging halide perovskite solar cells (PSCs). However, the use of soluble lead will raise environmental concerns. For the purpose of Pb recycling, herein, we report a reactant-recycling strategy to extract Pb from used LABs and synthesize high-purity PbI2. The recycled PbI2 shows smaller grain size, higher crystallinity, and higher thermal stability compared to the commercial sources. Perovskite films deposited with the high-quality PbI2 show larger grain size and fewer defects than the commercial ones. Consequently, the synthesized PbI2 enables a power conversation efficiency of 20.45% for the inverted MAPbI3 (MA= methylammonium) PSCs with excellent air stability. This work offers a novel strategy for lead recovery from LABs and a green path for the realization of high-performance PSCs with high defect tolerance.

13.
Cancer Lett ; 519: 172-184, 2021 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-34256096

RESUMEN

One mechanism for reactivation of androgen receptor (AR) activity after androgen deprivation therapy in castration-resistant prostate cancer (CRPC) is expression of splice variants such as ARv7 that delete the ligand binding domain and have constitutive activity. Exogenous overexpressed ARv7 can function as a homodimer or heterodimer with full length AR (ARfl), which is highly expressed with ARv7 in CRPC. However, the extent to which endogenous ARv7 function is dependent on heterodimerization with ARfl remains to be determined. We used double-crosslinking to stabilize AR complexes on chromatin in a CRPC cell line expressing endogenous ARfl and ARv7 (LN95 cells), and established that only trace levels of ARfl were associated with ARv7 on chromatin. Consistent with this result, depletion of ARfl with an AR degrader targeting the AR ligand binding domain did not decrease ARv7 binding to chromatin or its association with HOXB13, but did decrease overall AR transcriptional activity. Comparable results were obtained in CWR22RV1 cells, another CRPC cell line expressing ARfl and ARv7. These results indicate that ARv7 function in CRPC is not dependent on ARfl, and that both contribute independently to overall AR activity.


Asunto(s)
Neoplasias de la Próstata/genética , Receptores Androgénicos/genética , Línea Celular , Línea Celular Tumoral , Cromatina/genética , Células HEK293 , Proteínas de Homeodominio/genética , Humanos , Ligandos , Masculino , Próstata/metabolismo , Dominios Proteicos/genética
14.
ACS Appl Mater Interfaces ; 13(22): 26093-26101, 2021 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-34053218

RESUMEN

Defects at the grain boundary provide sites for nonradiative recombination in halide perovskite solar cells (PSCs). Here, by polymerization and fluorination of a Lewis acid of 4,4-bis(4-hydroxyphenyl)pentanoic acid, a fluorinated oligomer (FO-19) is synthesized and applied to passivate these defects in methlyammonium lead iodide (MAPbI3). It is demonstrated that the carboxyl bond of FO-19 was coordinated with Pb ions in the perovskite films to achieve a wrapping effect on the perovskite crystals. The defects of perovskite film are effectively passivated, and the undesirable nonradiative recombination is greatly inhibited. As a result, FO-19 gives a power conversion efficiency of 21.23% for the inverted MAPbI3-based PSCs, which is among the highest reported values in the literature. Meanwhile, the corresponding device with FO-19 exhibits significantly improved humidity and thermal stability. Therefore, this work offers insights into the realization of high-efficiency and stable PSCs through fluorinated additive engineering.

15.
Cancer Chemother Pharmacol ; 86(2): 295-305, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32743678

RESUMEN

PURPOSE: The HOX transcript antisense RNA (HOTAIR) has been reported to be aberrantly expressed in ovarian cancer (OC). Abnormal high expression level of HOTAIR has been found to be associated with poor overall survival of OC patients. Yet, the role of HOTAIR in paclitaxel resistance of OC is unclear. This study aims to investigate the effect, as well as the mechanism of HOTAIR in promoting paclitaxel resistance of OC. METHODS: Ovarian cancer cell lines with down-regulated and up-regulated expression of HOTAIR were, respectively, established. The expression of HOTAIR was confirmed by qRT-PCR. The sensitivity of ovarian cancer cells to paclitaxel was detected by MTT assays, colony formation, EdU assays, flow cytometry, and in vivo experiments. RESULTS: An increased expression level of HOTAIR was observed in ovarian cancer cell lines following treatment with paclitaxel. When the expression of HOTAIR was down-regulated, the proliferation of ovarian cancer cells was found to be inhibited, coupled with enhanced cell sensitivity to paclitaxel. Conversely, when the HOTAIR expression was up-regulated, an opposite effect was observed on the ovarian cancer cells. In addition, cell cycle arrest in G2/M phase was also shown to be accelerated upon HOTAIR suppression. Strikingly, our results also revealed that HOTAIR plays a regulatory role in the expression of checkpoint kinase 1 (CHEK1), and that the restored paclitaxel sensitivity through knockdown of HOTAIR can be weakened by CHEK1 up-regulation. Consistently, in vivo data confirmed that the therapeutic efficacy of paclitaxel can be enhanced through down-regulation of HOTAIR, and that CHEK1 is the down-stream target of HOTAIR in inducing paclitaxel resistance. CONCLUSION: HOTAIR confers paclitaxel resistance in epithelial ovarian cancer by increasing the protein level of CHEK1.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/metabolismo , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/farmacología , ARN Largo no Codificante/genética , Animales , Antineoplásicos Fitogénicos/farmacología , Apoptosis , Biomarcadores de Tumor/genética , Ciclo Celular , Movimiento Celular , Proliferación Celular , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/genética , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Elife ; 92020 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-32484436

RESUMEN

MCL1 has critical antiapoptotic functions and its levels are tightly regulated by ubiquitylation and degradation, but mechanisms that drive this degradation, particularly in solid tumors, remain to be established. We show here in prostate cancer cells that increased NOXA, mediated by kinase inhibitor activation of an integrated stress response, drives the degradation of MCL1, and identify the mitochondria-associated ubiquitin ligase MARCH5 as the primary mediator of this NOXA-dependent MCL1 degradation. Therapies that enhance MARCH5-mediated MCL1 degradation markedly enhance apoptosis in response to a BH3 mimetic agent targeting BCLXL, which may provide for a broadly effective therapy in solid tumors. Conversely, increased MCL1 in response to MARCH5 loss does not strongly sensitize to BH3 mimetic drugs targeting MCL1, but instead also sensitizes to BCLXL inhibition, revealing a codependence between MARCH5 and MCL1 that may also be exploited in tumors with MARCH5 genomic loss.


Asunto(s)
Antineoplásicos/farmacología , Proteínas de la Membrana/metabolismo , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Apoptosis , Línea Celular Tumoral , Humanos , Proteínas de la Membrana/genética , Mitocondrias/metabolismo , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/genética , Proteolisis , Proteínas Proto-Oncogénicas c-bcl-2/genética , Estrés Fisiológico , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación , Regulación hacia Arriba
17.
Mol Cancer Res ; 18(3): 436-447, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31722968

RESUMEN

Increased DNA damage repair is one of the mechanisms implicated in cisplatin resistance. Our previous study indicated that the deregulation of let-7e promoted cisplatin resistance and that let-7e could suppress DNA double-strand break repair in ovarian cancer. In this study, we further characterized the role of let-7e in DNA damage repair and cisplatin resistance in ovarian cancer, and investigated the underlying mechanisms. The alkaline and neutral comet assay indicated that let-7e impeded both DNA single- and double-strand break repairs through downregulating its target gene PARP1. In vitro and in vivo experiments provided evidence that the let-7e-PARP1-DNA repair axis was involved in the modulation of cisplatin sensitivity in ovarian cancer. Contrary to let-7e, PARP1 was overexpressed in cisplatin-resistant ovarian cancer tissues, and patients with high PARP1 expression exhibited poor progression-free survival (PFS) and overall survival (OS). Multivariate logistic and Cox regression analyses showed that let-7e and FIGO stage were independent prognostic factors for PFS and OS, whereas let-7e and PARP1 were able to independently predict chemotherapy response. Taken together, our results indicated that low expression of let-7e promoted DNA single- and double-strand break repairs and subsequently contributed to cisplatin resistance by relieving the suppression on PARP1 in ovarian cancer. IMPLICATIONS: Targeting the let-7e-PARP1-DNA repair axis might be an effective strategy for the treatment of chemoresistant ovarian cancer.


Asunto(s)
Cisplatino/farmacología , Daño del ADN , Reparación del ADN , MicroARNs/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Poli(ADP-Ribosa) Polimerasa-1/genética , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Regulación hacia Abajo , Resistencia a Antineoplásicos , Femenino , Xenoinjertos , Humanos , Ratones , MicroARNs/metabolismo , Estadificación de Neoplasias , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Poli(ADP-Ribosa) Polimerasa-1/biosíntesis , Transfección
18.
Nanomicro Lett ; 12(1): 156, 2020 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-34138179

RESUMEN

Organic-inorganic metal halide perovskite solar cells (PSCs) have recently been considered as one of the most competitive contenders to commercial silicon solar cells in the photovoltaic field. The deposition process of a perovskite film is one of the most critical factors affecting the quality of the film formation and the photovoltaic performance. A hot-casting technique has been widely implemented to deposit high-quality perovskite films with large grain size, uniform thickness, and preferred crystalline orientation. In this review, we first review the classical nucleation and crystal growth theory and discuss those factors affecting the hot-casted perovskite film formation. Meanwhile, the effects of the deposition parameters such as temperature, thermal annealing, precursor chemistry, and atmosphere on the preparation of high-quality perovskite films and high-efficiency PSC devices are comprehensively discussed. The excellent stability of hot-casted perovskite films and integration with scalable deposition technology are conducive to the commercialization of PSCs. Finally, some open questions and future perspectives on the maturity of this technology toward the upscaling deposition of perovskite film for related optoelectronic devices are presented.

19.
Curr Mol Pharmacol ; 12(4): 324-333, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31677258

RESUMEN

AIMS: The aim is to study the role of miR-675-5p coded by long non-coding RNA H19 in the development of Nasopharyngeal Cancer (NPC) and whether miR-675-5p regulates the invasion and metastasis of NPC through targeting SFN (14-3-3σ). The study further validated the relationship between H19, miR-675-5p and SFN in NPC and their relationship with the invasion and metastasis of NPC. METHODS: Western blot was used to detect the expression of 14-3-3σ protein in immortalized normal nasopharyngeal epithelial cells NP69 and different metastatic potential NPC cells, 6-10B and 5-8F. At the same time, to find out the relationship between 14-3-3σ protein and the expression of H19 and miR-675-5p, the expression of H19 and miR-675-5p in normal nasopharynx epithelial cells NP69 and varied nasopharyngeal carcinoma cells 6-10B and 5-8F were quantified by real-time PCR. MiR-675-5p mimic and inhibitor were transfected into NPC 6-10B to over-express and down-express miR-675-5p; miR-675-5p mimic negative control and inhibitor negative control were transfected into NPC 6-10B as control groups. The effect of over-expression and down-expression by miR-675-5p on the expression of 14-3-3σ protein was detected by Western blotting. The 3'-UTR segments of SFN, containing miR-675-5p binding sites were amplified by PCR and the luciferase activity in the transfected cells was assayed to detect whether SFN is the direct target of miR-675-5p. Transwell and scratch assays were used to verify the changes in NPC invasion and metastasis ability of mimics and inhibitors transfected with miR-675-5p. RESULTS: The expression of 14-3-3σ protein in normal nasopharynx epithelial cells NP69 is significantly higher than in varied nasopharyngeal carcinoma cells, 6-10B and 5-8F (P<0.05), and the 14-3-3σ protein levels in low-metastatic nasopharyngeal carcinoma cell 6-10B is higher than in high-metastatic nasopharyngeal carcinoma cell 5-8F. The expression of H19 and miR-675-5p are significantly higher in NPC cells than in NP69 cell (P<0.05). The expression of H19 and miR-675-5p in high-Metastatic nasopharyngeal carcinoma cell 5-8F was higher than in low-Metastatic nasopharyngeal carcinoma cell 6-10B. The expression of 14-3-3σ protein in miR-675-5p mimic cells was significantly lower than in mimic NC (negative control) group and blank control group. However, compared with the blank control group, mimic NC showed no significant difference in 14-3-3σ protein between the two groups. The miR-675-5p inhibitor group was significantly higher than the inhibitor NC group and the blank control group (p<0.05), but there was no significant difference in the expression of 14-3-3σ protein in the inhibitor NC group and the blank control group (p>0.05). Dual-luciferase reporter assay system shows the 3'-UTR segments of SFN containing miR-675-5p binding sites. SFN was the target gene of miR-675-5p. CONCLUSION: 14-3-3σ is downregulated in NPC and is involved in the development of NPC. H19 and miR- 675-5p are upregulated in NPC, which is related to the development of NPC. The over-expression of miR- 675-5p inhibits the expression of 14-3-3σ protein. SFN is the target gene of miR-675-5p. MiR-675-5p targets SFN, downregulates its protein expression and promotes the invasion and metastasis of NPC.


Asunto(s)
Proteínas 14-3-3/genética , Biomarcadores de Tumor/genética , Exorribonucleasas/genética , MicroARNs/genética , Neoplasias Nasofaríngeas/genética , Invasividad Neoplásica/genética , ARN Largo no Codificante/genética , Línea Celular Tumoral , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Nasofaríngeas/patología , Invasividad Neoplásica/patología
20.
Curr Mol Pharmacol ; 12(2): 105-114, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30569880

RESUMEN

BACKGROUND: Alterations in microRNAs (miRNAs) are related to the occurrence of nasopharyngeal carcinoma (NPC) and play an important role in the molecular mechanism of NPC. Our previous studies show low expression of 14-3-3σ (SFN) is related to the metastasis and differentiation of NPC, but the underlying molecular mechanisms remain unclear. METHODS: Through bioinformatics analysis, we find miR-597 is the preferred target miRNA of 14-3-3σ. The expression level of 14-3-3σ in NPC cell lines was detected by Western blotting. The expression of miR-597 in NPC cell lines was detected by qRT-PCR. We transfected miR-597 mimic, miR-597 inhibitor and 14-3-3σ siRNA into 6-10B cells and then verified the expression of 14-3-3σ and EMT related proteins, including E-cadherin, N-cadherin and Vimentin by western blotting. The changes of migration and invasion ability of NPC cell lines before and after transfected were determined by wound healing assay and Transwell assay. RESULTS: miR-597 expression was upregulated in NPC cell lines and repaired in related NPC cell lines, which exhibit a potent tumor-forming effect. After inhibiting the miR-597 expression, its effect on NPC cell line was obviously decreased. Moreover, 14-3-3σ acts as a tumor suppressor gene and its expression in NPC cell lines is negatively correlated with miR-597. Here 14-3-3σ was identified as a downstream target gene of miR-597, and its downregulation by miR-597 drives epithelial-mesenchymal transition (EMT) and promotes the migration and invasion of NPC. CONCLUSION: Based on these findings, our study will provide theoretical and experimental evidences for molecular targeted therapy of NPC.


Asunto(s)
Proteínas 14-3-3/metabolismo , Transición Epitelial-Mesenquimal , MicroARNs/metabolismo , Proteínas 14-3-3/antagonistas & inhibidores , Proteínas 14-3-3/genética , Antagomirs/metabolismo , Cadherinas/metabolismo , Diferenciación Celular , Línea Celular Tumoral , Movimiento Celular , Humanos , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Vimentina/metabolismo
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