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1.
Chem Asian J ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200561

RESUMO

Although metal-organic frameworks have proven to be excellent electrocatalytic materials, their application as electrode materials remains limited. The preparation of heterostructures is considered an effective method to improve catalytic activity. Herein, we describe the design and assembly of a dual-MOF heterostructure (CoNi-ZIF-67@Fe-MIL-100, denoted ZIF@MIL). Specifically, we grew a layer of MIL-100 in situ on a bimetallic ZIF-67 surface using a solvothermal method. We demonstrate that the ZIF@MIL has remarkable OER electrocatalytic performance, requiring a low overpotential and showing a small Tafel slope, compared to pure ZIF-67 and MIL-100 in 1.0 m KOH. More importantly, it has excellent operational durability for 50 h at 100 mA cm-2. The high catalytic activity of ZIF@MIL can be attributed to the heterostructure that can expose more active sites, the synergistic effect between ZIF-67 and MIL-100, and improvement of electron transfer ability. Our work provides a new way to design and prepare dual-MOF crystals with different structures as electrocatalysts.

2.
Nanoscale ; 12(40): 20811-20819, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33034596

RESUMO

Porous tungsten oxides (WO3) have been implemented in various application fields including catalysis, energy storage and conversion, and gas sensing. However, the construction of hierarchically ordered porous WO3 nanostructures with highly crystalline frameworks remains a great challenge. Herein, a confined interfacial micelle aggregating assembly approach has been developed for the synthesis of ordered macro-mesoporous WO3 (OMMW) nanostructures using three-dimensional SiO2 photonic crystals (PCs) as nanoreactors for the confined assembly of tungsten precursor and poly(ethylene oxide)-block-polystyrene (PEO-b-PS) template. After the heat treatment and etching processes, the obtained OMMW could achieve hierarchically ordered porous nanostructures with close-packed spherical mesopores (∼34.1 nm), interconnected macro-cavities (∼420 nm), high accessible surface areas (∼78 m2 g-1), and highly crystalline frameworks owing to the protection of dual templates. When OMMW nanostructures were assembled into gas sensors for the detection of H2S, the resulting sensors exhibited excellent comprehensive sensing performance, including a rapid response-recovery kinetics, in addition to high selectivity and long-term stability, which are significantly better than the previously reported WO3-based sensors. This study paves a promising way toward the development of hierarchically ordered porous semiconductors with large and interconnected porous channels for sensing applications.

3.
PLoS Comput Biol ; 16(10): e1008318, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33075080

RESUMO

Fibrillarin (FIB), a methyltransferase essential for life in the vast majority of eukaryotes, is involved in methylation of rRNA required for proper ribosome assembly, as well as methylation of histone H2A of promoter regions of rRNA genes. RNA viral progression that affects both plants and animals requires FIB proteins. Despite the importance and high conservation of fibrillarins, there little is known about the evolutionary dynamics of this small gene family. We applied a phylogenomic microsynteny-network approach to elucidate the evolutionary history of FIB proteins across the Tree of Life. We identified 1063 non-redundant FIB sequences across 1049 completely sequenced genomes from Viruses, Bacteria, Archaea, and Eukarya. FIB is a highly conserved single-copy gene through Archaea and Eukarya lineages, except for plants, which have a gene family expansion due to paleopolyploidy and tandem duplications. We found a high conservation of the FIB genomic context during plant evolution. Surprisingly, FIB in mammals duplicated after the Eutheria split (e.g., ruminants, felines, primates) from therian mammals (e.g., marsupials) to form two main groups of sequences, the FIB and FIB-like groups. The FIB-like group transposed to another genomic context and remained syntenic in all the eutherian mammals. This transposition correlates with differences in the expression patterns of FIB-like proteins and with elevated Ks values potentially due to reduced evolutionary constraints of the duplicated copy. Our results point to a unique evolutionary event in mammals, between FIB and FIB-like genes, that led to non-redundant roles of the vital processes in which this protein is involved.

4.
Endokrynol Pol ; 71(5): 367-375, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33125688

RESUMO

INTRODUCTION: The objective of this paper was to investigate the clinical features and pulmonary CT imaging features of COVID-19 patients with diabetes mellitus. MATERIAL AND METHODS: From January 16, 2020 to March 28, 2020, among the 568 cases of COVID-19 patients diagnosed in Xiaogan Central Hospital, 64 cases of COVID-19 patients with diabetes were selected as the diabetic group, and 64 cases of COVID-19 patients with age and gender matching without diabetes were selected as the non-diabetic group, and their clinical data and pulmonary CT characteristics were retrospectively analysed. RESULTS: Compared with the non-diabetic group, the proportion of patients in the diabetic group with chronic underlying disease was higher, and they were in more a serious condition at admission. Inflammation index and characteristics of glycolipid metabolism results showed that COVID-19 patients with diabetes mellitus were more likely to have elevated inflammatory markers and hypercoagulability, accompanied by hypoproteinaemia and glucose and lipid metabolism disorders. Treatment and clinic outcome results showed that the time of nucleic acid turning negative in the diabetic group was significantly longer than that in the non-diabetic group. Radiological data showed that COVID-19 combined with diabetes prolonged the time of detoxification in patients. CONCLUSION: COVID-19 patients with diabetes mellitus and chronic hypertension are associated with increased inflammatory markers and disorders of glucose and lipid metabolism. These patients tend to develop serious diseases, especially the rapid progression of CT lesions in the lungs of patients with a wide range ofinvolvement, and prolonged absorption and detoxification time.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Adulto , Idoso , Técnicas de Laboratório Clínico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
5.
J Environ Qual ; 49(2): 346-357, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33016421

RESUMO

Nonylphenol (NP) is considered a major contaminant that must be removed to enable safe and environmentally friendly land application of sewage sludge. Phytoremediation is a technology in which plants are used to remove and/or stabilize organic and inorganic contaminants present in the soil, municipal wastewater, and sewage sludge. In this study, a 391-d large pot experiment was conducted to remove NP from sewage sludge by phytoremediation using Zea mays L. 'Yunshi-5', Lolium perenne L., and co-cropping of the two plants. The fate of NP in the soil under the sewage sludge was assessed at the same time. At the end of the experiment, the NP levels in sludge from the various treatments were as follows: control (38.60%) > L. perenne (31.27%) > Z. mays (16.25%) > co-cropping (15.28%). Degradation followed an availability-adjusted first-order kinetics with a decreasing order of half-lives as follows: control (88.2 d) > L. perenne (87.3 d) > co-cropping (66.2 d) > Z. mays (59.1 d). The results indicated that Z. mays and co-cropping could both degrade NP. The concentrations of NP in tissues of different plants differed significantly. The mean bioconcentration factors for Z. mays and L. perenne were 0.16 and 3.69, respectively. Direct removal of NP from sewage sludge by plant uptake was negligible, as was downward movement of NP in the system. Moreover, NP was not detected in soils in any treatments at harvest.


Assuntos
Esgotos , Poluentes do Solo/análise , Biodegradação Ambiental , Fenóis/análise
6.
ACS Nano ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044056

RESUMO

Flexible and lightweight high-performance electromagnetic interference shielding materials with minimal thickness, excellent mechanical properties, and outstanding reliability are highly desired in the field of fifth-generation (5G) communication, yet remain extremely challenging to manufacture. Herein, we prepared an ultrathin densified carbon nanotube (CNT) film with superior mechanical properties and ultrahigh shielding effectiveness. Upon complete removal of impurities in pristine CNT film, charge separation in individual CNTs induced by polar molecules leads to strong CNT-CNT attraction and film densification, which significantly improve the electrical conductivity, shielding performance, and mechanical strength. The tensile strength is up to 822 ± 21 MPa, meanwhile the electrical conductivity is as high as 902,712 S/m, and the density is only 1.39 g cm-3. Notably, the shielding effectiveness is over 51 dB with a thickness of merely 1.85 µm in the broad frequency range of 4-18 GHz, and it reaches to ∼82 dB at 6.36 µm and ∼101 dB at 14.7 µm, respectively. Further, such CNT film exhibits excellent reliability after an extended period in strong acid/alkali, high temperature, and high humidity. It demonstrates the best overall performance among representative shielding materials by far, representing a critical breakthrough in the preparation of shielding film toward applications in wearable electronics and 5G communication.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32926275

RESUMO

To evaluate the relationship between coal-related carbon emissions (CCE) and economic growth, this paper analyzed the decoupling relationship between CCE and economic growth from national and provincial perspectives during period 1997-2016 through Tapio Decoupling Index. Then, to recognize its spatial characteristics during 1997-2016, gravity model was adopted to study the geographical changes of CCE. Finally, to identify the changes of (CCE) in China and reveal its internal driving forces, this paper employs the logarithmic mean Divisia index (LMDI) decomposition analysis to decompose decoupling indicator into six effects including emission factors, energy intensity, fossil energy structure, energy consumption structure, activity, and population at national and provincial levels. The results reflect that (1) CCE of China rose by 168.37% from 1997 to 2016, and reached the peak of 7948.43 Mton in 2013. The center of gravity has shifted from (114.64 E, 34.70 N) to (113.48 E, 35.06 N). (2) The decoupling curve showed an inverted "U" shape. The economic growth of 18 provinces has achieved a strong decoupling from CCE by 2016. Only Xinjiang, Shanxi, and Shaanxi's economic growth has increased the dependence on CCE. (3) Activity and energy intensity effects were the dominant factors driving and curbing the increase of decoupling indicator respectively.

8.
Appl Opt ; 59(27): 8335-8341, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32976419

RESUMO

At present, aluminum-based optical payloads are widely used in the aviation and aerospace field, and the demand for aluminum mirrors has become increasingly urgent in the visible light region. The main processing of an aluminum alloy mirror involves single-point diamond turning followed by a combined polishing process. Among these processes, magnetorheological finishing (MRF) is an important method for improving a surface figure. During the MRF process, excessive impurity contaminants are introduced into the surface of the aluminum mirror, thereby reducing surface reflectivity. In this paper, theoretical analysis and time-of-flight secondary ion mass spectrometry depth profiling were used to obtain the cause of pollution, and the process scheme of femtosecond laser cleaning was proposed. After verifying the feasibility, a new, to the best of our knowledge, process route was implemented on a Φ50mm aluminum mirror. Finally, the surface figure of RMS 0.022λ and the surface roughness of Ra 3.24 nm were obtained. In addition, reflectance in the visible light and near-infrared bands has increased by about 50%.

9.
Cell Death Dis ; 11(9): 794, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968045

RESUMO

Melanoma is the most life-threatening skin cancer with increasing incidence around the world. Although recent advances in targeted therapy and immunotherapy have brought revolutionary progress of the treatment outcome, the survival of patients with advanced melanoma remains unoptimistic, and metastatic melanoma is still an incurable disease. Therefore, to further understand the mechanism underlying melanoma pathogenesis could be helpful for developing novel therapeutic strategy. A20 is a crucial ubiquitin-editing enzyme implicated immunity regulation, inflammatory responses and cancer pathogenesis. Herein, we report that A20 played an oncogenic role in melanoma. We first found that the expression of A20 was significantly up-regulated in melanoma cell lines. Then, we showed that knockdown of A20 suppressed melanoma cell proliferation in vitro and melanoma growth in vivo through the regulation of cell-cycle progression. Moreover, A20 could potentiate the invasive and migratory capacities of melanoma cell in vitro and melanoma metastasis in vivo by promoting epithelial-mesenchymal transition (EMT). Mechanistically, we found that Akt activation mediated the oncogenic effect of A20 on melanoma development, with the involvement of glycolysis. What's more, the up-regulation of A20 conferred the acquired resistance to Vemurafenib in BRAF-mutant melanoma. Taken together, we demonstrated that up-regulated A20 promoted melanoma progression via the activation of Akt pathway, and that A20 could be exploited as a potential therapeutic target for melanoma treatment.

10.
Genes (Basel) ; 11(8)2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32751150

RESUMO

Excessive fat deposition in the hepatocytes, associated with excess dietary fat intake, was related to the occurrence of fatty livers in fish. miR-101b plays the important roles in controlling lipid metabolism, but the underlying mechanism at the post-transcriptional level remains unclear. The purpose of this study is to explore the roles and mechanism of miR-101b-mediating lipid deposition and metabolism in yellow catfish Pelteobagrus fulvidraco. We found that miR-101b directly targeted fatty acid translocase (cd36), caspase9 (casp9) and autophagy-related gene 4A (atg4a). Furthermore, using palmitic acid (PA) or oleic acid (OA) to incubate the primary hepatocytes of yellow catfish, we demonstrated that miR-101b inversely regulated cd36, casp9, and atg4a expression at the transcriptional level; the inhibition of miR-101b aggravated fatty acids (FAs, PA or OA)-induced lipid accumulation, indicating that miR-101b mediated FAs-induced variations of lipid metabolism in yellow catfish. Taken together, our study gave novel insight into the regulatory mechanism of lipid deposition and metabolism and might provide potential targets for the prevention and treatment of fatty livers in fish.

11.
Ecotoxicol Environ Saf ; 205: 111089, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32810645

RESUMO

Early molecular events after the exposure of heavy metals, such as aberrant DNA methylation, suggest that DNA methylation was important in regulating physiological processes for animals and accordingly could be used as environmental biomarkers. In the present study, we found that copper (Cu) exposure increased lipid content and induced the DNA hypermethylation at the whole genome level. Especially, Cu induced hypermethylation of glucose-regulated protein 78 (grp78) and peroxisome proliferator-activated receptor gamma coactivator-1α (pgc1α). CCAAT/enhancer binding protein α (C/EBPα) could bind to the methylated sequence of grp78, whereas C/EBPß could not bind to the methylated sequence of grp78. These synergistically influenced grp78 expression and increased lipogenesis. In contrast, DNA methylation of PGC1α blocked the specific protein 1 (SP1) binding and interfered mitochondrial function. Moreover, Cu increased reactive oxygen species (ROS) production, activated endoplasmic reticulum (ER) stress and damaged mitochondrial function, and accordingly increased lipid deposition. Notably, we found a new toxicological mechanism for Cu-induced lipid deposition at DNA methylation level. The measurement of DNA methylation facilitated the use of these epigenetic biomarkers for the evaluation of environmental risk.


Assuntos
Carpas/fisiologia , Cobre/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Carpas/metabolismo , Cobre/metabolismo , Estresse do Retículo Endoplasmático , Glucose/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Lipídeos , Metilação , Mitocôndrias/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ativação Transcricional , Regulação para Cima
12.
Commun Biol ; 3(1): 399, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32724075

RESUMO

The remains of ovarian follicles reported in nine specimens of basal birds represents one of the most remarkable examples of soft-tissue preservation in the Early Cretaceous Jehol Biota. This discovery was immediately contested and the structures alternatively interpreted as ingested seeds. Fragments of the purported follicles preserved in an enantiornithine (STM10-12) were extracted and subjected to multiple high-resolution analyses. The structures in STM10-12 possess the histological and histochemical characteristics of smooth muscles fibers intertwined together with collagen fibers, resembling the contractile structure in the perifollicular membrane (PFM) of living birds. Fossilized blood vessels, very abundant in extant PFMs, are also preserved. Energy Dispersive Spectroscopy shows the preserved tissues primarily underwent alumino-silicification, with minor mineralization via iron oxides. No evidence of plant tissue was found. These results confirm the original interpretation as follicles within the left ovary, supporting the interpretation that the right ovary was functionally lost early in avian evolution.

13.
J Trace Elem Med Biol ; 62: 126600, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32622174

RESUMO

BACKGROUND: Selenium (Se) appears in the selenoproteins in the form of selenocysteine (Sec) and is important for the growth and development of vertebrates. The present study characterized seven selenoproteins, consisting of the GPX1, GPX3, GPX4, SELENOW, SELENOP, TXNRD2 and TXNRD3 cDNAs in various tissues of yellow catfish, explored their regulation to dietary Se addition. METHODS: 3' and 5' RACE PCR were used to clone full-length cDNA sequences of seven selenoprotein genes (GPX1, GPX3, GPX4, SELENOW, SELENOP, TXNRD2 and TXNRD3). Their molecular characterizations were analyzed, including conservative motifs and the SECIS elements. The phylogenetic trees were generated through neighbor-joining (NJ) method with MEGA 6.0 with 1000 bootstrap replications. Quantitative real-time PCR was used to explore their mRNA tissue distribution in the heart, anterior intestine, dorsal muscle, head kidney, gill, liver, brain, spleen and mesenteric fat. Yellow catfish (mixed sex) were fed diets with dietary Se contents at 0.03 (low Se), 0.25 (adequate Se) and 6.39 (high Se) mg Se/kg, respectively, for 12 weeks, and their spleen, kidney, testis and brain were used for the determination of the mRNA levels of the seven selenoproteins. RESULTS: The seven selenoproteins had similar domains to their corresponding members of other vertebrates. They were widely expressed in nine tissues, including heart, liver, brain, spleen, head kidney, dorsal muscle, mesenteric fat, anterior intestine and gill, but showed tissue-dependent expression patterns. Dietary Se addition affected the expression of the seven genes in spleen, kidney, testis and brain tissues of yellow catfish. CONCLUSION: Taken together, our study demonstrated the characterization, expression and regulation of seven selenoproteins, which increased our understanding of the biological functions of Se and selenoproteins in fish.

14.
Yi Chuan ; 42(7): 613-631, 2020 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-32694102

RESUMO

Proteins are biological macromolecules essential for cells to maintain their metabolic activities. Proteins are synthesized during translation elongation, a synergistic process in which ribosomes decode the genetic information transmitted in mRNA, using tRNA. Numerous human diseases, such as neurodegenerative diseases and cancers, are known to be related to abnormal translation elongation. Translation elongation, as one of the two critical steps for the central dogma, used to be the focus of research in molecular biology. However, limitations in methodology had hindered further investigations on the dynamic process of translation elongation and its regulation. Recently, breakthroughs in methodology have revived this research field. Studies in the past decade or so have revealed that, beyond simple decoding of genetic information in mRNA, translation elongation entails sophisticated regulatory mechanisms and multifaceted biological consequences; such insights have provided a novel theoretical framework for understanding the maintenance of protein homeostasis and the development of diseases. In this review, we summarize the most updated methods that can be used to investigate the processes of translation elongation and highlight the mechanisms by which mRNA and protein sequences modulate the local rate of translation elongation. We further enumerate the consequences of dysregulation in translation elongation, from various aspects such as mRNA stability, protein synthesis and degradation, protein subcellular localization, and co-translational protein folding. We anticipate that this review will serve to draw the attention of scholars in various research fields to participate in the study of translation elongation.


Assuntos
Elongação Traducional da Cadeia Peptídica , Ribossomos , Humanos , Dobramento de Proteína , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Ribossomos/genética , Ribossomos/metabolismo
15.
Br J Nutr ; 124(12): 1241-1250, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-32600495

RESUMO

Dysregulation in hepatic lipid synthesis by excess dietary carbohydrate intake is often relevant with the occurrence of fatty liver; therefore, the thorough understanding of the regulation of lipid deposition and metabolism seems crucial to search for potential regulatory targets. In the present study, we examined TAG accumulation, lipid metabolism-related gene expression, the enzyme activities of lipogenesis-related enzymes, the protein levels of transcription factors or genes involving lipogenesis in the livers of yellow catfish fed five dietary carbohydrate sources, such as glucose, maize starch, sucrose, potato starch and dextrin, respectively. Generally speaking, compared with other carbohydrate sources, dietary glucose promoted TAG accumulation, up-regulated lipogenic enzyme activities and gene expressions, and down-regulated mRNA expression of genes involved in lipolysis and small ubiquitin-related modifier (SUMO) modification pathways. Further studies found that sterol regulatory element binding protein 1 (SREBP1), a key transcriptional factor relevant to lipogenic regulation, was modified by SUMO1. Mutational analyses found two important sites for SUMOylation modification (K254R and K264R) in SREBP1. Mutant SREBP lacking lysine 264 up-regulated the transactivation capacity on an SREBP-responsive promoter. Glucose reduced the SUMOylation level of SREBP1 and promoted the protein expression of SREBP1 and its target gene stearoyl-CoA desaturase 1 (SCD1), indicating that SUMOylation of SREBP1 mediated glucose-induced hepatic lipid metabolism. Our study elucidated the molecular mechanism of dietary glucose increasing hepatic lipid deposition and found that the SREBP-dependent transactivation was regulated by SUMO1 modification, which served as a new target for the transcriptional programmes governing lipid metabolism.

16.
Environ Sci Pollut Res Int ; 27(29): 36865-36877, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32572750

RESUMO

With China's economic transformation into a consumption-driven model, household CO2 emissions (HCEs) become an increasingly essential part of China's CO2 emissions. However, how will the HCEs change in urban and rural areas and what are the driving forces of HCEs through 2040 are not clear. In this paper, we project nation-level HCEs up to 2040 by the scenario analysis, and analyze the drivers of HCEs during 1997-2040 by the decomposition analysis. We find that the HCEs kept a persistent growth during 1997-2017 as energy intensity reduction and energy structure optimization cannot offset the rapid growth of consumption and population. During 2017-2040, in the current policy scenario, the rural HCEs will decrease, while the peaking of the total HCEs and urban HCEs would not be achieved. In the sustainable development scenario, the total HCEs, urban HCEs and rural HCEs will peak before 2030 and afterward decrease, because the energy intensity will induce a 51% and 76% reduction in the total HCEs and urban HCEs, respectively. Moreover, the decrease in the share of coal consumption due to the development of non-fossil fuels and natural gas will cause a more than 25% reduction in HCEs in the sustainable development scenario.


Assuntos
Dióxido de Carbono/análise , Características da Família , China , Carvão Mineral , Humanos , População Rural
17.
Eur J Med Chem ; 200: 112458, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32497962

RESUMO

The multidrug resistance (MDR) phenomenon in cancer cells is the major obstacle leading to failure of chemotherapy accompanied by the feature of intractable and recurrence of cancers. As significant contributors that cause MDR, ABC superfamily proteins can transport the chemotherapeutic drugs out of the tumor cells by the energy of adenosine triphosphate (ATP) hydrolysis, thereby reducing their intracellular accumulation. The ABC transports like ABCB1, ABCC1 and ABCG2 have been extensively studied to develop modulators for overcoming MDR. To date, no reversal agents have been successfully marketed for clinical application, and little information about the ABC proteins bound to specific inhibitors is known, which make the design of MDR inhibitors with potency, selectivity and low toxicity a major challenge. In recent years, it has been increasingly recognized that pyrimidine-based derivatives have the potential for reversing ABC-mediated MDR. In this review, we summarized the pyrimidine-based inhibitors of ABC transporters, and mainly focused on their structure optimizations, development strategies and structure-activity relationship studies in hope of providing a reference for medicinal chemists to develop new modulators of MDR with highly potency and fewer side effects.

18.
Environ Sci Pollut Res Int ; 27(25): 32100-32115, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32504444

RESUMO

As the largest carbon dioxide (CO2) emitter, China exists obvious regional inequality in per capita CO2 emissions. However, such inequality and its dynamic change for recent years have not been systematically studied. In this paper, we evaluate China's regional inequality in per capita CO2 emissions during 1997-2016 using the Theil index and decompose it into within-region and between-region components based on eight regions. Furthermore, we apply the decomposition analysis to explore the contribution of different factors to such inequality, including the carbonization index, energy intensity, energy structure, labor productivity, and employment rate. The results show that China's overall inequality in per capita CO2 emissions reduced first and increased thereafter during 1997-2016. Within-region inequality was the main source of overall inequality in 1997-2004, while between-region inequality contributed more during 2005-2016. Labor productivity and energy intensity were the two main drivers of overall inequality, but their contributions to the inequality between regions and within regions were quite different. Moreover, the impact of energy structure and carbonization index on regional inequality in per capita CO2 emissions significantly increased during 2012-2016, which was related to the efforts made by local governments to improve the energy mix. Policy implications were given according to the above conclusions to improve regional inequality in per capita CO2 emissions.


Assuntos
Dióxido de Carbono/análise , Desenvolvimento Econômico , China , Fatores Socioeconômicos
19.
Neurorehabil Neural Repair ; 34(7): 640-651, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32543269

RESUMO

Background. Ischemic stroke carries a high mortality rate and is a leading cause of severe neurological disability. However, the efficacy of current therapeutic options remains limited. Objective. We aimed to investigate the treatment efficacy of transcranial direct current stimulation (tDCS) in motor function rehabilitation after ischemic stroke and explore the underlying mechanisms. Methods. Male Sprague-Dawley rats with epicranial electrodes were used to establish pathogenetic model through temporary right middle cerebral artery occlusion (MCAO). Subsequently, animals were randomly divided into 4 groups: MCAO + tDCS/sham tDCS, Control + tDCS/sham tDCS. Animals in the groups with tDCS underwent 10 days of cathodal tDCS totally (500 µA, 15 minutes, once a day). During and after tDCS treatment, the motor functions of the animals, ischemic damage area, proliferation and differentiation of neural stem cells (NSCs), and distribution, and protein expression of Notch1 signaling molecules were detected. Results. The rehabilitation of MCAO-induced motor function deficits was dramatically accelerated by tDCS treatment. NSC proliferation in the subventricular zone (SVZ) was significantly increased after MCAO surgery, and tDCS treatment promoted this process. Additionally, NSCs probably migrated from the SVZ to the ischemic striatum and then differentiated into neurons and oligodendrocytes after MCAO surgery, both of which processes were accelerated by tDCS treatment. Finally, tDCS treatment inhibited the activation of Notch1 signaling in NSCs in the ischemic striatum, which may be involved in NSC differentiation in the MCAO model. Conclusion. Our results suggest that tDCS may exert therapeutic efficacy after ischemic stroke in a regenerative medical perspective.

20.
Cell Death Dis ; 11(6): 451, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532957

RESUMO

BRAF inhibitors (BRAFi) have shown remarkable clinical efficacy in the treatment of melanoma with BRAF mutation. Nevertheless, most patients end up with the development of BRAFi resistance, which strongly limits the clinical application of these agents. POU4F1 is a stem cell-associated transcriptional factor that is highly expressed in melanoma cells and contributes to BRAF-activated malignant transformation. However, whether POU4F1 contributes to the resistance of melanoma to BRAFi remains poorly understood. Here, we report that over-expressed POU4F1 contributed to the acquired resistance of melanoma cells to Vemurafenib. Furthermore, POU4F1 promoted the activation of ERK signaling pathway via transcriptional regulation on MEK expression. In addition, POU4F1 could increase the expression of MITF to retain the resistance of melanoma cells to BRAFi. Collectively, our findings reveal that POU4F1 re-activates the MAPK pathway by transcriptional regulation on MEK expression and promotes MITF expression, which ultimately results in the resistance to BRAFi in melanoma. Our study supports that POU4F1 is a potential combined therapeutic target with BRAFi therapy for melanoma.

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