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1.
Nucleic Acids Res ; 51(D1): D70-D79, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36162821

RESUMO

Cohesin is a multifunctional protein responsible for transcriptional regulation and chromatin organization. Cohesin binds to chromatin at tens of thousands of distinct sites in a conserved or tissue-specific manner, whereas the function of cohesin varies greatly depending on the epigenetic properties of specific chromatin loci. Cohesin also extensively mediates cis-regulatory modules (CRMs) and chromatin loops. Even though next-generation sequencing technologies have provided a wealth of information on different aspects of cohesin, the integration and exploration of the resultant massive cohesin datasets are not straightforward. Here, we present CohesinDB (https://cohesindb.iqb.u-tokyo.ac.jp), a comprehensive multiomics cohesin database in human cells. CohesinDB includes 2043 epigenomics, transcriptomics and 3D genomics datasets from 530 studies involving 176 cell types. By integrating these large-scale data, CohesinDB summarizes three types of 'cohesin objects': 751 590 cohesin binding sites, 957 868 cohesin-related chromatin loops and 2 229 500 cohesin-related CRMs. Each cohesin object is annotated with locus, cell type, classification, function, 3D genomics and cis-regulatory information. CohesinDB features a user-friendly interface for browsing, searching, analyzing, visualizing and downloading the desired information. CohesinDB contributes a valuable resource for all researchers studying cohesin, epigenomics, transcriptional regulation and chromatin organization.


Assuntos
Proteínas Cromossômicas não Histona , Bases de Dados Genéticas , Transcriptoma , Humanos , Fator de Ligação a CCCTC/genética , Fator de Ligação a CCCTC/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cromatina/genética , Epigenoma , Transcriptoma/genética , Coesinas
2.
BMC Plant Biol ; 24(1): 306, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38644480

RESUMO

Linkage maps are essential for genetic mapping of phenotypic traits, gene map-based cloning, and marker-assisted selection in breeding applications. Construction of a high-quality saturated map requires high-quality genotypic data on a large number of molecular markers. Errors in genotyping cannot be completely avoided, no matter what platform is used. When genotyping error reaches a threshold level, it will seriously affect the accuracy of the constructed map and the reliability of consequent genetic studies. In this study, repeated genotyping of two recombinant inbred line (RIL) populations derived from crosses Yangxiaomai × Zhongyou 9507 and Jingshuang 16 × Bainong 64 was used to investigate the effect of genotyping errors on linkage map construction. Inconsistent data points between the two replications were regarded as genotyping errors, which were classified into three types. Genotyping errors were treated as missing values, and therefore the non-erroneous data set was generated. Firstly, linkage maps were constructed using the two replicates as well as the non-erroneous data set. Secondly, error correction methods implemented in software packages QTL IciMapping (EC) and Genotype-Corrector (GC) were applied to the two replicates. Linkage maps were therefore constructed based on the corrected genotypes and then compared with those from the non-erroneous data set. Simulation study was performed by considering different levels of genotyping errors to investigate the impact of errors and the accuracy of error correction methods. Results indicated that map length and marker order differed among the two replicates and the non-erroneous data sets in both RIL populations. For both actual and simulated populations, map length was expanded as the increase in error rate, and the correlation coefficient between linkage and physical maps became lower. Map quality can be improved by repeated genotyping and error correction algorithm. When it is impossible to genotype the whole mapping population repeatedly, 30% would be recommended in repeated genotyping. The EC method had a much lower false positive rate than did the GC method under different error rates. This study systematically expounded the impact of genotyping errors on linkage analysis, providing potential guidelines for improving the accuracy of linkage maps in the presence of genotyping errors.


Assuntos
Mapeamento Cromossômico , Genótipo , Triticum , Triticum/genética , Mapeamento Cromossômico/métodos , Locos de Características Quantitativas , Ligação Genética , Técnicas de Genotipagem/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos
3.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34850813

RESUMO

Eukaryotic genomes are organized in a three-dimensional spatial structure. In this regard, the development of chromosome conformation capture methods has enabled studies of chromosome organization on a genomic scale. Hi-C, the high-throughput chromosome conformation capture method, can reveal a population-averaged, hierarchical chromatin structure. The typical Hi-C analysis uses a two-dimensional (2D) contact matrix that indicates contact frequencies between all possible genomic position pairs. Oftentimes, however, such a 2D matrix is not amenable to handling quantitative comparisons, visualizations and integrations across multiple datasets. Although several one-dimensional (1D) metrics have been proposed to depict structural information in Hi-C data, their effectiveness is still underappreciated. Here, we first review the currently available 1D metrics for individual Hi-C samples or two-sample comparisons and then discuss their validity and suitable analysis scenarios. We also propose several new 1D metrics to identify additional unique features of chromosome structures. We highlight that the 1D metrics are reproducible and robust for comparing and visualizing multiple Hi-C samples. Moreover, we show that 1D metrics can be easily combined with epigenome tracks to annotate chromatin states in greater details. We develop a new framework, called HiC1Dmetrics, to summarize all 1D metrics discussed in this study. HiC1Dmetrics is open-source (github.com/wangjk321/HiC1Dmetrics) and can be accessed from both command-line and web-based interfaces. Our tool constitutes a useful resource for the community of chromosome-organization researchers.


Assuntos
Cromatina , Cromossomos , Cromatina/genética , Cromossomos/genética , Genoma , Genômica/métodos , Conformação Molecular
4.
Cardiovasc Diabetol ; 23(1): 164, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724987

RESUMO

Dynamin-related protein 1 (Drp1) is a crucial regulator of mitochondrial dynamics, the overactivation of which can lead to cardiovascular disease. Multiple distinct posttranscriptional modifications of Drp1 have been reported, among which S-nitrosylation was recently introduced. However, the detailed regulatory mechanism of S-nitrosylation of Drp1 (SNO-Drp1) in cardiac microvascular dysfunction in diabetes remains elusive. The present study revealed that mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) was consistently upregulated in diabetic cardiomyopathy (DCM) and promoted SNO-Drp1 in cardiac microvascular endothelial cells (CMECs), which in turn led to mitochondrial dysfunction and cardiac microvascular disorder. Further studies confirmed that MAP4K4 promoted SNO-Drp1 at human C644 (mouse C650) by inhibiting glutathione peroxidase 4 (GPX4) expression, through which MAP4K4 stimulated endothelial ferroptosis in diabetes. In contrast, inhibition of MAP4K4 via DMX-5804 significantly reduced endothelial ferroptosis, alleviated cardiac microvascular dysfunction and improved cardiac dysfunction in db/db mice by reducing SNO-Drp1. In parallel, the C650A mutation in mice abolished SNO-Drp1 and the role of Drp1 in promoting cardiac microvascular disorder and cardiac dysfunction. In conclusion, our findings demonstrate that MAP4K4 plays an important role in endothelial dysfunction in DCM and reveal that SNO-Drp1 and ferroptosis activation may act as downstream targets, representing potential therapeutic targets for DCM.


Assuntos
Cardiomiopatias Diabéticas , Dinaminas , Células Endoteliais , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Células Cultivadas , Circulação Coronária , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/enzimologia , Cardiomiopatias Diabéticas/etiologia , Modelos Animais de Doenças , Dinaminas/metabolismo , Dinaminas/genética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Células Endoteliais/enzimologia , Células Endoteliais/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Mitocôndrias Cardíacas/enzimologia , Processamento de Proteína Pós-Traducional , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética
5.
Ecotoxicol Environ Saf ; 281: 116631, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38941658

RESUMO

The contamination of arsenic (As) in aqueous environments has drawn widespread attention, and iron compounds may largely alter the migration ability of As. However, the stability of As(III) in Fe-As system with the intervention of organic matter (OM) remains unclear. Herein, we had explored the co-precipitation and co-oxidation processes of As-Fe system by using batch experiments combined with Fourier Transform Infrared Spectroscopy (FTIR) and X-ray Photoelectron Spectroscopy (XPS) in this research. The precipitation quantity of As(III) increased (28.85-92.41 %) when the As/Fe ratio decreased, and increased (24.20-64.20 %) with pH increased. The main active substance for oxidizing As(III) was H2O2, which was produced in the As-Fe system. FTIR and XPS revealed that As(III) was first oxidized in neutral, and then absorbed and enteredthe interior of Fe(OH)3 colloids. But under alkaline conditions, As(III) was adsorbed by Fe (Oxyhydr) oxides firstly, and then oxidized. The intervention of OM would inhibit the redistribution process of As(III) in aqueous environments. Functional groups and unsaturation of the carbon chain were the dominant factors that affected the precipitation and oxidation processes of As(III), respectively. Co-existing ions (especially PO43-) also signally affected the precipitation quantity of As(Ⅲ) in the system and, when coexisting with OM, could exacerbate this process. The influence of co-existing ions on the redistributive process of As(III) in the As-Fe system with/without OM were as follows: PO43- > SO42- > mixed ions > SiO32-. Moreover, high concentration of OM and PO43- might lead to morphological alterations of As, acting as a threat to aqueous environments. In summary, the present findings were to further understand and appreciate the changes of As toxicity in the aqueous environments. Particularly, the coexistence of OM and As can potentially increase the risk to drinking water safety.

6.
J Basic Microbiol ; 64(1): 68-80, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37717245

RESUMO

Endophytic fungi are an important source of novel antitumor substances. Previously, we isolated an endophytic fungus, Alternaria alstroemeria, from the medicinal plant Artemisia artemisia, whose crude extracts strongly inhibited A549 tumor cells. We obtained a transformant, namely AaLaeAOE26 , which completely loses its antitumor activity due to overexpression of the global regulator AaLaeA. Re-sequencing analysis of the genome revealed that the insertion site was in the noncoding region and did not destroy any other genes. Metabolomics analysis revealed that the level of secondary antitumor metabolic substances was significantly lower in AaLaeAOE26 compared with the wild strain, in particular flavonoids were more downregulated according to the metabolomics analysis. A further comparative transcriptome analysis revealed that a gene encoding FAD-binding domain protein (Fla1) was significantly downregulated. On the other hand, overexpression of AaFla1 led to significant enhancement of antitumor activity against A549 with a sevenfold higher inhibition ratio than the wild strain. At the same time, we also found a significant increase in the accumulation of antitumor metabolites including quercetin, gitogenin, rhodioloside, liensinine, ginsenoside Rg2 and cinobufagin. Our data suggest that the global regulator AaLaeA negatively affects the production of antitumor compounds via controlling the transcription of AaFla1 in endophytic A. alstroemeria.


Assuntos
Alstroemeria , Alternaria , Alternaria/genética , Metabolismo Secundário , Flavonoides/metabolismo , Endófitos
7.
Theor Appl Genet ; 136(11): 232, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37875655

RESUMO

KEY MESSAGE: Four stable QTL for adult-plant resistance (APR) to powdery mildew were identified on chromosome arms 1DL, 2BS, 2DL, and 6BL in the widely grown Chinese wheat cultivar Bainong 64. These QTL had no effect on response to stripe rust or leaf rust. Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a devastating fungal disease. Seedlings of Chinese wheat Bainong 64 are susceptible to Bgt, but adult plants have maintained resistance since it was released in 1996. A population of 171 recombinant inbred lines (RILs) developed from cross Jingshuang 16/Bainong 64 (JS16/BN64) was used to dissect genetic components of powdery mildew resistance. A genetic map comprising 5383 polymorphic markers was constructed using the 15 K SNP chip and kompetitive allele-specific PCR (KASP) markers. Composite interval mapping identified four stable QTL with favorable alleles all from BN64 on chromosome arms 1DL, 2BS, 2DL, and 6BL in at least four environments. They accounted for 8.3%, 13.8%, 14.4%, and 9.0% of the total phenotypic variation explained (PVE) in maximum, respectively. QPmjbr.caas-1DL, situated about 22 Mb from centromere, is probably a new QTL. QPmjbr.caas-2DL located near the end of arm 2DL and explained the largest PVE. Using genetic maps populated with KASP markers, QPmjbr.caas-2BS and QPmjbr.caas-6BL were fine mapped to a 1.8 cM genetic intervals spanning 13.6 Mb (76.0-89.6 Mb) and 1.7 cM and 4.9 Mb (659.9-664.8 Mb), respectively. The four QTL independent of stripe rust and leaf rust resistance were validated for powdery mildew resistance in another RIL population related to BN64 and a cultivar panel using representative KASP markers. Since BN64 has been a leading cultivar and an important breeding parent in China, the QTL and markers reported in this study will be useful for marker-assisted selection of APR.


Assuntos
Basidiomycota , Locos de Características Quantitativas , Mapeamento Cromossômico , Fenótipo , Triticum/genética , Triticum/microbiologia , Resistência à Doença/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Melhoramento Vegetal
8.
Nanotechnology ; 35(2)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37820612

RESUMO

The sluggish kinetics of anodic oxygen evolution reaction (OER) is regarded as the main bottleneck for ineffective hydrogen production efficiency, limiting the industrial application of electrochemical water splitting. Substituting the OER by urea electrooxidation reaction (UOR) and simultaneously developing highly active and economical bifunctional electrocatalyst for UOR and hydrogen evolution reaction (HER) is a promising method to realize energy-saving hydrogen production and urea-rich wastewater abatement. Herein, self-supporting Ni-NiO film grown on Ti mesh (Ni-NiO/TM) was successfully prepared by a facile cathodic electrodeposition method with using nickel acetate as the only raw material. Electrodeposition process was optimized by modulating the electrodeposition time and potential. x-ray diffraction, scanning electron microscopy, transmission electron microscopy, x-ray photoelectron spectroscopy and Raman characterization revealed the optimized Ni-NiO/TM was comprised of crystalline Ni and amorphous NiO and its morphology exhibited nanosphere structure, assembled by nanosheets. Ni-NiO/TM sample prepared under the potential of -1.5 V and deposition time of 10 min illustrated the lowest UOR potential of 1.34 V at 50 mA cm-2and robust stability, superior to the recently reported literatures. Furthermore, the HER potential was only -0.235 V to drive the current density of 50 mA cm-2. The cell voltage of urea-assisted electrolysis for hydrogen production in Ni-NiO/TM||Ni-NiO/TM two-electrode system only required 1.56 V to deliver 50 mA cm-2, obviously lower than that (>1.72 V) for overall water splitting. This work demonstrated the potential of Ni-based material as bifunctional electrocatalyst for energy-saving H2production by urea-rich wastewater electrolysis.

9.
Environ Toxicol ; 38(12): 2926-2938, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37565766

RESUMO

Environmental hazards are an increasing concern due to the rapid pace of industrialization. Among these hazards, noise and carbon monoxide (CO) are common risk factors and have been shown to cause serious health problems. However, existing studies focused on the individual effects of noise and CO exposure and the combined effects of these two factors remain poorly understood. Our study aimed to examine the combined effects of noise and CO exposure on testicular function by constructing individual and combined exposure models. Our findings indicated that combined exposure to noise and CO was associated with a higher risk of testicular damage and male reproductive damage when compared to exposure alone. This was evidenced by poorer semen quality and more severe pathological damage to the testis. This combined exposure led to higher levels of oxidative stress and apoptosis in the testes, with bioinformatics analyses suggesting the signaling pathways involved in these responses. Specifically, activation of the P53 signaling pathway was found to contribute to the testicular damage caused by the combined exposure. Encouragingly, pterostilbene (PTE), a novel phytochemical, alleviated combined exposure-induced testicular damage by reducing oxidative stress and germ cell apoptosis. Overall, we identified joint reproductive toxicity resulting from the exposure to noise and CO, and found that PTE is a promising potential treatment for injuries caused by these factors. The cover image is based on the Research Article Effects and possible mechanisms of combined exposure to noise and carbon monoxide on male reproductive system in rats by Yingqing Li et al., https://doi.org/10.1002/tox.23927.


Assuntos
Monóxido de Carbono , Análise do Sêmen , Ratos , Masculino , Animais , Monóxido de Carbono/toxicidade , Testículo , Células Germinativas , Reprodução , Estresse Oxidativo
10.
J Environ Manage ; 348: 119331, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37883836

RESUMO

The pulp production process generates a CaCO3-rich solid waste known as white mud (WM), and its improper disposal is a cause for global concern. The present study investigates the composition, microstructure, and thermal decomposition characteristics of WM and proposes a strategy for replacing limestone with WM for iron ore sintering. Granulation and sinter pot tests were performed to evaluate the influence of added WM on the granulation and sintering processes. We assess the feasibility of using WM as a flux and discuss the mechanism through which WM affects the mineral phase and strength of the sinter based on metallographic and micropore observations. The results indicate that the sintering rate remains stable after replacing 50% of the limestone with WM via moisture control, and the quality and production indicators of the sinter do not change. Moreover, the mineral phase and microporosity remain similar to the basic case without WM, and the comprehensive index decreased by only 5.5%. Overall, this study demonstrates that it is feasible to replace 50% of limestone with WM in industrial sintering plants, which could significantly increase our WM disposal capacity and bring additional economic benefits.


Assuntos
Carbonato de Cálcio , Ferro , Ferro/química , Resíduos Sólidos
11.
Fish Shellfish Immunol ; 124: 472-479, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35483596

RESUMO

Granzyme (Gzm) B and perforin, both as cytotoxic proteins, can collaborate to induce the death of target cells as well as the microbes. They were originally discovered in cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells and confer the cytotoxic activities of these cells. In the present study, the coding sequences of a granzyme b-like (gcgzmbl) and a perforin-like (gcprfl) genes were cloned from grass carp (Ctenopharyngodon idellus) and their specific antibodies were subsequently prepared and validated. The mRNA and protein expression of these two cytotoxic proteins in grass carp peripheral blood neutrophils was demonstrated by quantitative PCR (qPCR) and immunofluorescence staining, respectively. In the same cell model, expression of gcGzmbl and gcPrfl was stimulated by grass carp interleukin (Il)-2 in a dose- and time-dependent manners and Erk, NF-κB and Stat5 pathways were found to be involved in the regulation of Il-2 on the genes' expression. Additionally, glycolysis was proved to play a role in the stimulation of Il-2 on gcGzmbl and gcPrfl expression in peripheral blood neutrophils. As combating the invading microorganisms is one of the main functions of neutrophils, the roles of gcGzmbl and gcPrfl in the anti-bacterial activities of grass carp peripheral blood neutrophils were explored. Results showed that immunoneutralization of gcGzmbl or gcPrfl significantly attenuated the antimicrobial abilities of the neutrophils enhanced by Il-2. These findings shed a light on the expression, regulation and functions of granzyme B- and perforin-like proteins in fish peripheral blood neutrophils and enrich the understanding of Il-2 function in fish innate immunity.


Assuntos
Carpas , Doenças dos Peixes , Animais , Carpas/genética , Carpas/metabolismo , Proteínas de Peixes , Granzimas/genética , Granzimas/metabolismo , Neutrófilos/metabolismo , Perforina/genética , Transdução de Sinais/genética
12.
Environ Res ; 206: 112301, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736639

RESUMO

The sluggish Ni(II)/Ni(III) redox cycle does not benefit perxymonosulfate (PMS) activation for recalcitrant pollutant degradation. To solve this problem, a heterogeneous catalyst, Cu0.2Ni0.8O/SBA-15 (CNS), was constructed to activate PMS for decomposing two sulfonamide antibiotics, sulfachlorpyridazine (SACP) and sulfapyridine (SAP). SACP and SAP were completely degraded over Cu0.2Ni0.8O/SBA-15/PMS (CNSP) after 90 min. O2.- was the dominant active species involved in the degradation of SACP and SAP. Structural analysis and elemental valence state observations indicated that Cu(Ⅰ) provided electrons through Cu-O-Ni bonds to realize the charge compensation for Ni(Ⅲ) in the CNSP system. Thus, the in situ Cu(I)/Cu(II) promoting the Ni(II)/Ni(III) cycle could accelerate the PMS activation. This work provides new insights into the electron transfer between transition metals and the charge compensation mechanism for PMS activation. The degradation mechanism was proposed based on the XPS results before and after the reaction, a radical quenching test, and an EPR test. Combined with the SACP and SAP degradation intermediates identified by LC-MS, we suggest that the choice of treatment process depends on the occurrence of a steric hindrance effect between the molecular structure of the degradation target and free radicals.


Assuntos
Antibacterianos , Cobre , Cobre/química , Níquel , Peróxidos , Dióxido de Silício , Sulfonamidas
13.
Antonie Van Leeuwenhoek ; 115(8): 1085-1100, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35789442

RESUMO

A number of studies have demonstrated that endophytic fungi have the potential to produce antitumor active substances with novel structures and significant activities. In our previous studies, we isolated a Fusarium strain from the stem of the medicinal plant Nothapodytes pittosporoides (Oliv.). In this study, we identified this strain as Fusarium solani and found that its crude extract has significant antitumor activity against human alveolar adenocarcinoma cells (A549). We overexpressed the global regulatory factor VeA in F. solani (VeAOE), resulting in a significant increase in antitumor activity. The MTT assay results showed that the inhibition rate of the VeAOE mutant extract on A549 cancer cells was significantly higher than that of the WT extract, as the IC50 decreased from 369.22 to 285.89 µg/mL, and the apoptosis ratio was significantly increased by approximately 4.86-fold. In VeAOE, accumulation of alkaloids, terpenoids, carboxylic acid derivatives, phenols and flavonoid metabolites with potential antitumor activity was significantly increased compared with WT based on metabolomic analysis. Additionally, transcriptome analysis found that the expression patterns of 48 genes related to antitumor activity were significantly changed in VeAOE, mainly involving glycosyl hydrolases, the Zn(2)-Cys(6) class, cytochrome P450 monooxygenase, 3-isopropylmalate dehydratase, and polyketide synthases. These results suggested that VeA mediated the antitumor activity of the metabolites in F. solani HB1-J1 by regulating multiple metabolic pathways.


Assuntos
Fusarium , Plantas Medicinais , Fungos , Fusarium/química , Humanos , Plantas Medicinais/microbiologia
14.
Ecotoxicol Environ Saf ; 238: 113569, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35512470

RESUMO

Sertoli cells play a pivotal role in the complex spermatogenesis process. This study aimed to investigate the effects of PM2.5 on Sertoli cells using the TM4 cell line and a real time whole-body PM2.5 exposure mouse model, and further explore the underlying mechanisms through the application of metabolomics and transcriptomics. The results in vivo and in vitro showed that PM2.5 reduced Sertoli cells number in seminiferous tubules and inhibited cell proliferation. PM2.5 exposure also induced Sertoli cell dysfunction by increasing androgen binding protein (ABP) concentration, reducing the blood-testis barrier (BTB)-related protein expression, and decreasing glycolysis capacity and lactate production. The results of transcriptomics, metabolomics, and integrative analysis of multi-omics in the TM4 Sertoli cells revealed the activation of xenobiotic metabolism, and the disturbance of glutathione and purine metabolism after PM2.5 exposure. Further tests verified the reduced GSH/GSSG ratio and the elevation of xanthine oxidase (XO) activity in the PM2.5-exposed TM4 cells, indicating that excessive reactive oxygen species (ROS) was generated via metabolic disorder caused by PM2.5. Moreover, the redox imbalance was proved by the increase in the mitochondrial ROS level, superoxide dismutase (SOD) and catalase (CAT) activity, as well as the activation of the Nrf2 antioxidative pathway. Further study found that the redox imbalance caused by PM2.5 induced DNA damage response and cell cycle arrest. Additionally, PM2.5 induced ferroptosis through iron overload and lipid peroxidation. Taken all together, our study provided new insights for understanding proliferation inhibition and dysfunction of TM4 Sertoli cells exposed to PM2.5 via metabolic disorder and redox imbalance-mediated DNA damage response and ferroptosis.


Assuntos
Ferroptose , Células de Sertoli , Animais , Antioxidantes/metabolismo , Apoptose , Proliferação de Células , Dano ao DNA , Glutationa/metabolismo , Masculino , Metabolômica , Oxirredução , Material Particulado/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reprodução , Células de Sertoli/metabolismo , Transcriptoma
15.
Molecules ; 27(7)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35408691

RESUMO

(1) Background: pancreatic cancer is one of the most serious cancers due to its rapid and inevitable fatality, which has been proved very difficult to treat, compared with many other common cancers. Thus, developing an effective therapeutic strategy, especially searching for potential drugs, is the focus of current research. The exact mechanism of rutin in pancreatic cancer remains unknown. (2) Method: three pancreatic cancer cell lines were used to study the anti-pancreatic cancer effect of rutin. The potent anti-proliferative, anti-migration and pro-apoptotic properties of rutin were uncovered by cell viability, a wound-healing migration assay, and a cell apoptosis assay. High-throughput sequencing technology was used to detect the change of miRNAs expression. Immunoblotting analysis was used to detect the expression of apoptotic proteins. (3) Results: CCK-8 and EDU assays revealed that rutin significantly inhibited pancreatic cancer cells' proliferation (p < 0.05). A wound-healing assay showed that rutin significantly suppressed pancreatic cancer cells' migration (p < 0.05). A flow cytometric assay showed that rutin could promote pancreatic cancer cells' apoptosis. Intriguingly, rutin significantly upregulated miR-877-3p expression to repress the transcription of Bcl-2 and to induce pancreatic cancer cell apoptosis. Accordingly, rutin and miR-877-3p mimics could promote apoptotic protein expression. (4) Conclusions: our findings indicate that rutin plays an important role in anti-pancreatic cancer effects through a rutin-miR-877-3p-Bcl-2 axis and suggests a potential therapeutic strategy for pancreatic cancer.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Rutina/farmacologia , Neoplasias Pancreáticas
16.
Angew Chem Int Ed Engl ; 61(21): e202201616, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35266263

RESUMO

Inorganic heteroanionic materials are attracting increasing attention for exploring new nonlinear optical (NLO) materials because they could better satisfy the necessary but conflicting properties of NLO crystals, e.g. large SHG response and wide band-gap. Up to now, the reports on heteroanionic NLO materials have mainly focused on ultraviolet or visible oxide-based fluoroborates, fluorophosphates, borate-phosphates and borate-iodates. However, chalcogenides containing different kinds of anionic groups have barely been reported. Herein, we have synthesized the first oxychalcogenide-carbonate, Sr3 [SnOSe3 ][CO3 ] that contains two different kinds of anionic groups, [SnOSe3 ] and [CO3 ]. It crystallizes in a noncentrosymmetric space group and exhibits fascinating NLO properties, including a large SHG response (≈1×AGS), sufficient birefringence (0.12 @1064 nm), wide band-gap (3.46 eV) and high laser damage threshold (240 MW cm-2 ). These make Sr3 [SnOSe3 ][CO3 ] a promising NLO crystal.

17.
J Exp Bot ; 72(4): 1307-1320, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33070191

RESUMO

Popcorn (Zea mays L. var. Everta) is the most ancient type of cultivated maize. However, there is little known about the genetics of popping-related traits based on genotyping-by-sequencing (GBS) technology. Here, we characterized the phenotypic variation for seven popping-related traits in maize kernels among 526 CIMMYT inbred lines (CMLs). In total, 155 083 high-quality single nucleotide polymorphism (SNP) markers were identified by a GBS approach. Several trait-associated loci were detected by genome-wide association study for color, popping expansion volume, shape, pericarp, flotation index, floury/vitreous, and protein content, explaining a majority of the observed phenotypic variance, and these were validated by a diverse panel comprising 764 tropical landrace accessions. Sixty two of the identified loci were recognized to have undergone selection. On average, there was a 55.27% frequency for alleles that promote popping in CMLs. Our work not only pinpoints previously unknown loci for popping-related traits, but also reveals that many of these loci have undergone selection. Beyond establishing a new benchmark for the genetics of popcorn, our study provides a foundation for gene discovery and breeding. It also presents evidence to investigate the role of a gradual loss of popping ability as a by-product of diversification of culinary uses throughout the evolution of teosinte-to-modern maize.


Assuntos
Estudo de Associação Genômica Ampla , Zea mays , Mapeamento Cromossômico , Fenótipo , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Zea mays/genética
18.
Nanotechnology ; 32(30)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33784655

RESUMO

Developing a cost-effective and efficient bifunctional electrocatalyst with simple synthesis strategy for hydrazine sensing and H evolution reaction (HER) is of utmost importance. Herein, a three-dimensional porous Cu-doped metallic Ni coating on Ti mesh (Ni(Cu) coating/TM) was successfully electrodeposited by a facile electrochemical method. Electrochemical etching of the electrodeposited Ni(Cu) coating with metallic Ni and Cu mixed phase on a Ti mesh contributed to the formation of a three-dimensional porous Cu-doped metallic Ni coating. Owing to the large specific surface area and enhanced electroconductivity caused by the porous structure and Cu doping, respectively, the developed Ni(Cu) coating/TM exhibited superior hydrazine sensing performance and electrocatalytic activity toward hydrogen evolution reaction (HER). The Ni(Cu) coating/TM electrode presented a good sensitivity of 3909µA mM-1cm-2and two relatively broad linear ranges from 0.004 mM to 2.915 mM and from 2.915 mM to 5.691 mM as well as a low detection limit of 1.90µM. In addition, the Ni(Cu) coating/TM required a relatively low HER overpotential of 140 mV to reach -10 mA cm-2and exhibited robust durability in alkaline solution. The excellent hydrazine electrooxidation and HER performance guarantee its promising application in hydrazine detection and energy conversion.

19.
Ecotoxicol Environ Saf ; 216: 112189, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33819782

RESUMO

The largest source of resistant bacteria or viruses is the overuse and misuse of antibiotics in humans and animals. These resistant bacteria or viruses may evolve into superbacteria or superviruses, which causes global plague. Therefore, it is significant to find a highly efficiency and low-cost method to eliminate antibiotics in water environment from inappropriate discharge. Here, a highly active and highly stable heterogeneous catalyst, Cu0.76Co2.24O4/SBA-15 (CCS) was prepared for peroxymonosulfate (PMS) activation in aim of decomposing persistent sulfapyridine (SPD). The reaction mechanism was thoroughly investigated via in situ quenching test and in situ electron paramagnetic resonance. Four reactive species, SO4·-, O2·-, 1O2 and ·OH were generated in Cu0.76Co2.24O4/SBA-15/PMS (CCSP) system. The SO4·- and O2·- were dominant active species responsible for SPD degradation. Co(Ⅱ)↔Co(Ⅲ)↔Co(Ⅱ) redox reaction cycle was constructed due to the different redox potential of Co(Ⅱ)/Co(Ⅲ), HSO5-/SO4∙-, and HSO5-/SO5∙-. Interestingly, Cu(Ⅰ) could urge the redox reaction cycle for PMS activation to be more thermodynamically feasible. Therefore, CCS possessed a highly catalytic activity and excellent stability. Meanwhile, the anions interference test indicated Cl-, NO3-, HCO3-, and H2PO4- had almost no inhibitory effect on SPD degradation over this catalytic system. We sincerely expected that this catalyst system would be applied extensively into antibiotics degradation in real water bodies.

20.
Bioorg Med Chem ; 28(2): 115093, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31859028

RESUMO

AIMS: In Sheng Nong's herbal classic in China, Rhizoma coptidisa(RC) could be used to treat Atopic dermatitsb(AD), but its core ingredient(s) and mechanism remains unknown. The present study aimed to find out the ingredients against AD and expound its mechanisms. MATERIALS AND METHODS: Seven alkaloids were isolated from RC to compare the inhibition against HaCaT cells by MTT assays and apoptosis of cells stimulated with TNF-α/IFN-γ by flow cytometry. The effects of target alkaloids against AD were evaluated on DNCBc (2,4-dinitrochlorobenzene)-induced atopic dermatitis in mice. KEY FINDINGS: Seven alkaloids were isolated from RC successfully. The results from MTT and flow cytometry indicated that among these alkaloids, only magnoflorine d(MAG) had no obvious toxicity on cells, but could inhibit the apoptosis of the cells stimulated with TNF-α/IFN-γ. Further animal experiments confirmed that MAG significantly attenuated the AD-like symptom and inhibited the AD-induced increases in IgE/IL-4, as compared with control (P < 0.01). Moreover, MAG reduced the low Δψme(mitochondrial membrane potential) in HaCaT cells. The results of western blotting proved that MAG inhibited apoptosis of keratinocytes through decreasing the expressions of CTSBf (cathepsin B), Cyte Cg (cytochrome C), Bid and caspase-3/7/8/9. SIGNIFICANCE: Overall, MAG inhibited apoptosis by decreasing the expression of apoptotic pathway-related proteins, and laid a foundation for the study of AD mechanisms.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Aporfinas/farmacologia , Coptis/química , Dermatite Atópica/tratamento farmacológico , Queratinócitos/efeitos dos fármacos , Animais , Anti-Inflamatórios/administração & dosagem , Aporfinas/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/metabolismo , Dinitroclorobenzeno , Relação Dose-Resposta a Droga , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Relação Estrutura-Atividade
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