Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 836
Filtrar
1.
Cell Metab ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33798471

RESUMO

Serine metabolism promotes tumor oncogenesis and regulates immune cell functions, but whether it also contributes to antiviral innate immunity is unknown. Here, we demonstrate that virus-infected macrophages display decreased expression of serine synthesis pathway (SSP) enzymes. Suppressing the SSP key enzyme phosphoglycerate dehydrogenase (PHGDH) by genetic approaches or by treatment with the pharmaceutical inhibitor CBR-5884 and by exogenous serine restriction enhanced IFN-ß-mediated antiviral innate immunity in vitro and in vivo. Mechanistic experiments showed that virus infection or serine metabolism deficiency increased the expression of the V-ATPase subunit ATP6V0d2 by inhibiting S-adenosyl methionine-dependent H3K27me3 occupancy at the promoter. ATP6V0d2 promoted YAP lysosomal degradation to relieve YAP-mediated blockade of the TBK1-IRF3 axis and, thus, enhance IFN-ß production. These findings implicate critical functions of PHGDH and the key immunometabolite serine in blunting antiviral innate immunity and also suggest manipulation of serine metabolism as a therapeutic strategy against virus infection.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33802909

RESUMO

Using panel data from 11 regions (9 provinces and two cities) in the Yangtze River Economic Belt (YREB) during 2002-2017, the regional differences in and spatial characteristics of the green efficiency of water resources along the YREB were analyzed. The undesirable outputs slacks-based measure-data envelopment analysis, Malmquist index, and social network analysis models were employed. A dynamic panel using a system generalized method of moments model was established to empirically examine the main factors influencing green efficiency. The results show the following. First, temporally, green efficiency fluctuates while showing an overall decreasing trend; spatially, green efficiency generally decreases in this order: downstream, upstream, then midstream. Second, the change in the total factor productivity (TFP) index shows an overall increasing trend, with TFP improvement mainly attributable to technology. Third, green efficiency shows a significant spatial correlation. All provinces are in the spatial correlation network, and the network, as a whole, has strong stability. Finally, water resource endowment, water prices, government environmental control strength, and the water resources utilization structure have a significant impact on green efficiency.

3.
Sensors (Basel) ; 21(7)2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33800532

RESUMO

Hyperspectral image (HSI) super-resolution (SR) is a challenging task due to its ill-posed nature, and has attracted extensive attention by the research community. Previous methods concentrated on leveraging various hand-crafted image priors of a latent high-resolution hyperspectral (HR-HS) image to regularize the degradation model of the observed low-resolution hyperspectral (LR-HS) and HR-RGB images. Different optimization strategies for searching a plausible solution, which usually leads to a limited reconstruction performance, were also exploited. Recently, deep-learning-based methods evolved for automatically learning the abundant image priors in a latent HR-HS image. These methods have made great progress for HS image super resolution. Current deep-learning methods have faced difficulties in designing more complicated and deeper neural network architectures for boosting the performance. They also require large-scale training triplets, such as the LR-HS, HR-RGB, and their corresponding HR-HS images for neural network training. These training triplets significantly limit their applicability to real scenarios. In this work, a deep unsupervised fusion-learning framework for generating a latent HR-HS image using only the observed LR-HS and HR-RGB images without previous preparation of any other training triplets is proposed. Based on the fact that a convolutional neural network architecture is capable of capturing a large number of low-level statistics (priors) of images, the automatic learning of underlying priors of spatial structures and spectral attributes in a latent HR-HS image using only its corresponding degraded observations is promoted. Specifically, the parameter space of a generative neural network used for learning the required HR-HS image to minimize the reconstruction errors of the observations using mathematical relations between data is investigated. Moreover, special convolutional layers for approximating the degradation operations between observations and the latent HR-HS image are specifically to construct an end-to-end unsupervised learning framework for HS image super-resolution. Experiments on two benchmark HS datasets, including the CAVE and Harvard, demonstrate that the proposed method can is capable of producing very promising results, even under a large upscaling factor. Furthermore, it can outperform other unsupervised state-of-the-art methods by a large margin, and manifests its superiority and efficiency.

4.
PLoS Pathog ; 17(3): e1009396, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33730056

RESUMO

Mosquito viruses cause unpredictable outbreaks of disease. Recently, several unassigned viruses isolated from mosquitoes, including the Omono River virus (OmRV), were identified as totivirus-like viruses, with features similar to those of the Totiviridae family. Most reported members of this family infect fungi or protozoans and lack an extracellular life cycle stage. Here, we identified a new strain of OmRV and determined high-resolution structures for this virus using single-particle cryo-electron microscopy. The structures feature an unexpected protrusion at the five-fold vertex of the capsid. Disassociation of the protrusion could result in several conformational changes in the major capsid. All these structures, together with some biological results, suggest the protrusions' associations with the extracellular transmission of OmRV.

5.
Nano Lett ; 21(6): 2476-2486, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33683126

RESUMO

Epstein-Barr virus (EBV) infection is a global health concern infecting over 90% of the population. However, there is no currently available vaccine. EBV primarily infects B cells, where the major glycoprotein 350 (gp350) is the main target of neutralizing antibodies. Given the advancement of nanoparticle vaccines, we describe rationally designed vaccine modalities presenting 60 copies of gp350 on self-assembled nanoparticles in a repetitive array. In a mouse model, gp350s on lumazine synthase (LS) and I3-01 adjuvanted with MF59 or aluminum hydroxide (Alhydrogel) elicited over 65- to 133-fold higher neutralizing antibody titers than the corresponding gp350 monomer to EBV. Furthermore, immunization with gp350D123-LS and gp350D123-I3-01 vaccine induced a Th2-biased response. For the nonhuman primate model, gp350D123-LS in MF59 elicited higher titers of total IgG and neutralizing antibodies than the monomeric gp350D123. Overall, these results support gp350D123-based nanoparticle vaccine design as a promising vaccine candidate for potent protection against EBV infection.

6.
Retina ; 41(4): 834-843, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33755650

RESUMO

PURPOSE: This study aimed to investigate the effect of intravitreal conbercept (IVC) injections on the aqueous humor concentrations of angiogenic and inflammatory cytokines in patients with macular edema (ME) due to central retinal vein occlusion and to determine whether changes in cytokine levels after IVC are associated with the development of rebound ME. METHODS: Forty-nine patients with ME caused by central retinal vein occlusion were included in this retrospective study. Monthly doses of IVC were administered for three months, followed by a Pro Re Nata dosing regimen. Rebound ME was defined as ≥110% increase in the foveal thickness compared with the baseline. Whenever injections were administered, aqueous humor samples were obtained. Multiplex bead assay was used to measure seven angiogenic and inflammatory cytokines in aqueous humor samples. RESULTS: At baseline, patients with central retinal vein occlusion showed significantly higher aqueous humor concentrations of vascular endothelial growth factor, placental growth factor, monocyte chemoattractant protein-1, platelet-derived growth factor-AA, IL-6, IL-8, and IL-12. At 1-month and 2-month follow-up after IVC, significantly decreased concentrations of all cytokines were observed. During the 12-month follow-up period, 6 of the 49 eyes (12.2%) showed rebound ME after IVC. Patients with rebound ME showed significantly elevated levels of inflammatory but not angiogenic cytokines. CONCLUSION: Angiogenic and inflammatory cytokines were overexpressed in patients with ME caused by central retinal vein occlusion. Conbercept treatment influenced the concentrations of various inflammatory cytokines and reduced aqueous vascular endothelial growth factor and placental growth factor concentrations. Rebound ME may occur due to disruption of the balance between angiogenic and inflammatory cytokines and an accompanying excess of inflammatory cytokines but not angiogenic cytokines, after antivascular endothelial growth factor therapy.

7.
Int J Biol Macromol ; 179: 377-387, 2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33652044

RESUMO

In order to understand the effects of emulsion particle sizes on the properties of novel konjac glucomannan (KGM)-based emulsion films, four types of Pickering emulsions with different oil phase (10%, 30%, 50% and 70%, v/v) were prepared by the same stabilizers (2% BCNs/SPI colloidal particles dispersions) and added into the film-forming solutions to keep the same final oil content (0.2%, w/v) in all KGM-based emulsion films. The results showed that the average particle sizes of the prepared Pickering emulsion increased with the increase of the oil phase in emulsion system. The microstructure analyses indicated that the KGM-based emulsion films became smoother as the emulsion particle sizes increased. Moreover, the contact angle values of KGM-based emulsion films slightly increased with the increase of the emulsion particle sizes, while the thermal stability of KGM-based films was not significantly affected by the particle sizes. Furthermore, the KGM-based emulsion films formed mainly through the hydrogen bond interactions as analyzed by FTIR. In addition, with the increase of the emulsion particle sizes, physical and mechanical properties of KGM-based emulsion films were significantly affected. Taken together, these results suggested that the particle sizes of Pickering emulsions had remarkable effects on the properties of KGM-based emulsion films.

8.
Inorg Chem ; 60(7): 4723-4732, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33733761

RESUMO

The construction of novel electrocatalysts for efficient and economic electrochemical sensors is continuously a significant conceptual barrier for the point-of-care technology. Binary metal oxides with heterostructures have gained plenty of attention due to their promising physicochemical properties. Herein, we develop a rapid and sensitive electrochemical probe for the detection of flufenamic acid (FFA) by using a zinc manganate (ZnMnO)-modified electrode. The formation of ZnMnO was confirmed by various analytical techniques, such as X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, and field-emission scanning electron microscopy with energy dispersive X-ray spectroscopy and elemental mapping. The ZnMnO-based electrocatalyst, which was used for the electrochemical detection of FFA, shows better performance than the previously reported electrode materials. The ZnMnO assay shows a linear quantitative range from 0.05 to 116 µM with a limit of detection of 0.003 µM and sensitivity of 0.385 µA µM-1 cm-2. Its good electrochemical performance can be ascribed to the large surface area, rapid charge mass transfer, copious active sites, and high carrier mobility. The electrochemical study displays that the fabricated ZnMnO-based sensor has the potential to be applied in the clinical analysis. This work constructs an advanced functional electrode material with a microscale architecture for the point-of-care technology.

9.
Int J Oral Sci ; 13(1): 10, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753723

RESUMO

C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

10.
Sci China Chem ; : 1-16, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33679901

RESUMO

Chemically functionalized gas-filled bubbles with a versatile micro/nano-sized scale have witnessed a long history of developments and emerging applications in disease diagnosis and treatments. In combination with ultrasound and image-guidance, micro/nanobubbles have been endowed with the capabilities of biomedical imaging, drug delivery, gene transfection and disease-oriented therapy. As an external stimulus, ultrasound (US)-mediated targeting treatments have been achieving unprecedented efficiency. Nowadays, US is playing a crucial role in visualizing biological/pathological changes in lives as a reliable imaging technique and a powerful therapeutic tool. This review retrospects the history of ultrasound, the chemistry of functionalized agents and summarizes recent advancements of functional micro/nanobubbles as US contrast agents in preclinical and trans-clinical research. Latest ultrasound-based treatment modalities in association with functional micro/nanobubbles have been highlighted as their great potentials for disease precision therapy. It is believed that these state-of-the-art micro/nanobubbles will become a booster for ultrasound medicine and visualizable guidance to serve future human healthcare in a more comprehensive and practical manner.

11.
J Invertebr Pathol ; : 107565, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33676966

RESUMO

Entomopathogenic fungi have been used as important biological control agents throughout the world. To improve the biocontrol efficacy of entomopathogenic fungi, many genes have been used to improve fungal virulence or tolerance to adverse conditions via modulating their expression with strong promoters. The Magas1 gene is specifically expressed during appressorium formation and contributes to the virulence in Metarhizium acridum. In this study, we analyzed the functional region of the promoter of Magas1 gene (PMagas1) in M. acridum using 5'-deletion technique with enhanced green fluoresces protein (EGFP) as a reporter. Results showed the full length of the PMagas1 was at least 897 bp. Two regions (-897 to -611 bp and -392 to -328 bp) were essential for the activity of PMagas1. An engineered M. acridum strain was constructed with PMagas1 driving the expression of a subtilisin-like proteinase gene Pr1A (PMagas1-PR1A). Bioassay showed that the virulence was significantly increased in PMagas1-PR1A strain compared to wild type strain. Pmagas1 promoter is suitable for the overexpression of some genes during the infection of entomopathogenic fungi, which avoids the waste of nutritional resources and the influence on other fungal characteristics during the saprophytic process of constitutive promoter.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33763996

RESUMO

BACKGROUND: Malnutrition and muscle wasting are common features frequently observed in pancreatic ductal adenocarcinoma (PDAC) patients with cancer cachexia. They are associated with reduced survival and quality of life. Nutrition therapy is an important part of multimodal cancer care in PDAC. However, due to the complexity of nutrition assessment, only 30-60% of patients with nutritional risks receive nutritional treatment at present. It is important to identify biomarkers that may be used to improve management of PDAC-associated malnutrition. Serum insulin-like growth factor binding protein 2 (IGFBP2) has emerged as a potential serum biomarker in a variety of tumours. However, its association with malnutrition and muscle wasting in PDAC is unclear. METHODS: We evaluated the tumour IGFBP2 expression and serum IGFBP2 level in 98 PDAC patients using immunohistochemistry and enzyme-linked immunosorbent assay and analysed the correlation between them. Furthermore, we explored the relationship between IGFBP2 of both tumour and serum and nutritional status (Patient-Generated Subjective Global Assessment and skeletal muscle index). Pan02 IGFBP2 stable transfection cell lines, Pan02 PLV-IGFBP2 cells, and PLKO-IGFBP2 cells were injected subcutaneously into the flank of C57BL/6 mouse. Serum IGFBP2 levels, food intake, and body weight of these mice were measured. The degree of muscle atrophy is characterized by haematoxylin and eosin, Oil Red O, and Masson's trichrome staining. The mRNA and protein expression of several essential muscle-related signal proteins such as atrogin-1 and muscle RING finger 1 was measured. RESULTS: Among 98 patients, we found that tumour IGFBP2 expression is related to plasma IGFBP2 levels (rs  = 0.562, P < 0.001), and they significantly increased among patients with Patient-Generated Subjective Global Assessment ≥9 and correlated with overall survival. Moreover, serum IGFBP2 level is negatively correlated with skeletal muscle index (rs  = -0.600, P < 0.001) and Hounsfield units (rs  = -0.532, P < 0.001). In mice injected with Pan02 PLV-IGFBP2 cell, circulating IGFBP2 was elevated while body weight and food intake were decreased when compared with Pan02 PLV-Control group. These mice also exhibited significantly aggravated muscle fibre atrophy, lipid deposition, and increased collagen tissue, and the expression of mRNA and protein of atrogin-1 and muscle RING finger 1 in the gastrocnemius muscle is increased. Conversely, these symptoms were alleviated in the PLKO-IGFBP2 group. CONCLUSIONS: In the current study, there is a significant correlation between serum IGFBP2 levels, malnutrition, and muscle atrophy in PDAC. Our results suggested that serum IGFBP2 level might be a promising biomarker and intervention targets for PDAC-associated severe malnutrition and muscle wasting.

13.
J Environ Manage ; 287: 112283, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33706087

RESUMO

Plastic waste pollution has been identified as a serious global issue, posing environmental risks in terms of massive waste generation, ocean pollution, and increases in greenhouse gas (GHG) emissions. Despite documented environmental impacts, it remains debatable whether the global plastic waste trade (GPWT) for reutilization and recycling, as part of the global circular economy (CE), has historically contributed to environmental benefits. To investigate if historical GPWT has contributed to environmental benefits in terms of reductions of GHG emissions, this study analyzed GPWT between China and trading countries through their trajectories, characteristics and driving forces of reductions of GHG emissions between 1992 and 2017. Results indicated an increasing trend of reductions of GHG emissions in GPWT between China and trading countries over 25 years. A net reduction of 8.27 million metric tons carbon dioxide equivalent (CO2e) was observed in 2012, nearly 84 times levels observed in 1992. Policy implications after China's recent ban of imports of GPWT in December 2017 and recent changes of GPWT to other Asian countries are discussed. Dramatic changes in sustainable approaches to GPWT for reutilization and recycling are required.

14.
Water Res ; 196: 116990, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33725645

RESUMO

Noroviruses (NoVs) are the leading cause of acute gastroenteritis (AGE) outbreaks. Since 2014, novel genetic variants of NoV have been continuously identified and have caused a sharp increase in the number of AGE outbreaks. The specific geographical distribution and expanding genetic diversity of NoV has posed a challenge to conventional surveillance. Here, we describe the long-term dynamic correlation between NoV distribution in sewage and in the local population through the molecular surveillance of NoV in Guangdong, 2013-2018. The relative viral loads of the GI and GII genotypes in sewage were calculated through RT-PCR. A high-throughput sequencing method and operational taxonomic unit (OTU) clustering pipeline were developed to illustrate the abundances of different genotypes and genetic variants in sewage. Our results showed that the NoV viral loads and the emergence of new variants in sewage were closely associated with NoV outbreak risks in the population. Compared with the outbreaks surveillance, the dominance of the newly emerged variants, GII.P17-GII.17 and GII.P16-GII.2, could be detected one or two months ahead in sewage of a hub city. In addition, the dynamics of pre-epidemic variants, which were rarely detected in clinics, could be captured through sewage surveillance, thus improving our understanding of the origin and evolution of these novel epidemic variants. Our data highlight that sewage surveillance could provide nearly real-time and high-throughput data on NoV circulation in the community. With the advances in sequencing techniques, the sewage surveillance system could also be extended to other related infectious diseases.

15.
FEMS Microbiol Lett ; 368(5)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33693941

RESUMO

Elizabethkingia are found to cause severe neonatal meningitis, nosocomial pneumonia, endocarditis and bacteremia. However, there are few studies on Elizabethkingia genus by comparative genomic analysis. In this study, three species of Elizabethkingia were found: E. meningoseptica, E. anophelis and E. miricola. Resistance genes and associated proteins of seven classes of antibiotics including beta-lactams, aminoglycosides, macrolides, tetracyclines, quinolones, sulfonamides and glycopeptides, as well as multidrug resistance efflux pumps were identified from 20 clinical isolates of Elizabethkingia by whole-genome sequence. Genotype and phenotype displayed a good consistency in beta-lactams, aminoglycosides and glycopeptides, while contradictions exhibited in tetracyclines, quinolones and sulfonamides. Virulence factors and associated genes such as hsp60 (htpB), exopolysaccharide (EPS) (galE/pgi), Mg2+ transport (mgtB/mgtE) and catalase (katA/katG) existed in all clinical and reference strains. The functional analysis of the clusters of orthologous groups indicated that 'metabolism' occupied the largest part in core genome, 'information storage and processing' was the largest group in both accessory genome and unique genome. Abundant mobile elements were identified in E. meningoseptica and E. anophelis. The most significant finding in our study was that a single clone of E. anophelis had been circulating within diversities of departments in a clinical setting for nearly 18 months.

16.
Thorac Cancer ; 12(7): 1106-1114, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33565277

RESUMO

BACKGROUND: ALK rearrangement is a very rare subset of squamous cell carcinoma (SCC) and one of the clinical features in patients is lack of data. Here, we report eight patients diagnosed with SCC of the lung harboring ALK rearrangement. METHODS: We collected primary NSCLC samples at the Beijing Chest Hospital between January 2012 and December 2018 for Ventana (D5F3) immunohistochemical detection. Among the 148 patients was diagnosed ALK-rearranged non small cell lung cancer (NSCLC), only eight cases was SCC. We collected patients information from electronic patent records (EPRs). RESULTS: The eight cases of SCC were diagnosed by immunohistochemistry (IHC). Two were given crizotinib as second-line therapy. One patient had stable disease (SD) and progression-free survival (PFS) of six months. The other patient had progressive disease (PD) but PFS was only one month. The side effects were tolerable. This report identified 31 cases of ALK rearrangement in SCC patients from a literature search (including the eight patients in this study). These fusion genes are often seen in a younger age group (mean age: 55.6 years) and non-smokers (18/31, 58.1%). A total of 20 cases received an ALK inhibitor as first- or second-line treatment which included 11 with a partial response (PR), four with SD, and five with PD. The DCR and ORR was 75.0% (15/20) and 55.0% (11/20), respectively. The median duration time of therapy was 6.4 ± 4.4 months. CONCLUSIONS: Patients with ALK-rearranged SCC obtained clinical benefit from ALK-inhibitor therapy, especially those who were non-smokers and whose tumors had been identified by IHC+/FISH+.

17.
J Cell Biol ; 220(4)2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33605979

RESUMO

Endocytosed proteins can be delivered to lysosomes for degradation or recycled to either the trans-Golgi network or the plasma membrane. It remains poorly understood how the recycling versus degradation of cargoes is determined. Here, we show that multiple extracellular stimuli, including starvation, LPS, IL-6, and EGF treatment, can strongly inhibit endocytic recycling of multiple cargoes through the activation of MAPK11/14. The stress-induced kinases in turn directly phosphorylate SNX27, a key regulator of endocytic recycling, at serine 51 (Ser51). Phosphorylation of SNX27 at Ser51 alters the conformation of its cargo-binding pocket and decreases the interaction between SNX27 and cargo proteins, thereby inhibiting endocytic recycling. Our study indicates that endocytic recycling is highly dynamic and can crosstalk with cellular stress-signaling pathways. Suppression of endocytic recycling and enhancement of receptor lysosomal degradation serve as new mechanisms for cells to cope with stress and save energy.

18.
Trends Biochem Sci ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33579564

RESUMO

Liquid-liquid phase separation (LLPS) has emerged in recent years as an important physicochemical process for organizing diverse processes within cells via the formation of membraneless organelles termed biomolecular condensates. Emerging evidence now suggests that the formation and regulation of biomolecular condensates are also intricately linked to cancer formation and progression. We review the most recent literature linking the existence and/or dissolution of biomolecular condensates to different hallmarks of cancer formation and progression. We then discuss the opportunities that this condensate perspective provides for cancer research and the development of novel therapeutic approaches, including the perturbation of condensates by small-molecule inhibitors.

19.
J Colloid Interface Sci ; 590: 144-153, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33524715

RESUMO

Addressing the inherent holes transport limitation of BiVO4 photoanode is crucial to achieve efficient photoelectrochemical (PEC) water splitting. The construction of the hole-transfer bridge between co-catalysts and BiVO4 photoanode could be an effective way to overcome sluggish hole-transfer kinetics of BiVO4 photoanode. Herein, CxNy/BiVO4 photoanode was prepared by coupling carbon nitride hydrogel (CNH) containing unsaturated N on the BiVO4 photoanode during annealing. CxNy/BiVO4 photoanode exhibited excellent PEC performance and stability. Photoelectrochemical tests proved that the coupling of CxNy accelerated holes transfer and enhanced oxygen evolution kinetics. X-ray photoelectron spectroscopy (XPS) and theoretical calculations confirmed the existence of the BiNV bond between BiVO4 photoanode and CxNy, which could serve as the hole-transfer bridge to significantly accelerate separation and transfer of carriers driven by the interfacial electric field. Moreover, it was found that the coupling of CxNy effectively inhibited the dissociation of metal ions through changing their coordination environment, resulting in the excellent stability of CxNy/BiVO4 photoanode. This result provides unique insights into vital roles of the interfacial structure, which might have a significant impact on the construction of PEC devices.

20.
Cell Death Dis ; 12(2): 149, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542201

RESUMO

To support cellular homeostasis and mitigate chemotherapeutic stress, cancer cells must gain a series of adaptive intracellular processes. Here we identify that NUPR1, a tamoxifen (Tam)-induced transcriptional coregulator, is necessary for the maintenance of Tam resistance through physical interaction with ESR1 in breast cancers. Mechanistically, NUPR1 binds to the promoter regions of several genes involved in autophagy process and drug resistance such as BECN1, GREB1, RAB31, PGR, CYP1B1, and regulates their transcription. In Tam-resistant ESR1 breast cancer cells, NUPR1 depletion results in premature senescence in vitro and tumor suppression in vivo. Moreover, enforced-autophagic flux augments cytoplasmic vacuolization in NUPR1-depleted Tam resistant cells, which facilitates the transition from autophagic survival to premature senescence. Collectively, these findings suggest a critical role for NUPR1 as a transcriptional coregulator in enabling endocrine persistence of breast cancers, thus providing a vulnerable diagnostic and/or therapeutic target for endocrine resistance.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...