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Cis-regulatory elements (CREs) fine-tune gene transcription in eukaryotes. CREs with sequence variations play vital roles in driving plant or crop domestication. However, how global sequence and structural variations (SVs) are responsible for multilevel changes between indica and japonica rice (Oryza sativa) is still not fully elucidated. To address this, we conducted multiomic studies using MNase hypersensitivity sequencing (MH-seq) in combination with RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and bisulfite sequencing (BS-seq) between the japonica rice variety Nipponbare (NIP) and indica rice variety 93-11. We found that differential MNase hypersensitive sites (MHSs) exhibited some distinct intrinsic genomic sequence features between NIP and 93-11. Notably, through MHS-genome-wide association studies (GWAS) integration, we found that key sequence variations may be associated with differences of agronomic traits between NIP and 93-11, which is partly achieved by MHSs harboring CREs. In addition, SV-derived differential MHSs caused by transposable element (TE) insertion, especially by noncommon TEs among rice varieties, were associated with genes with distinct functions, indicating that TE-driven gene neo- or subfunctionalization is mediated by changes of chromatin openness. This study thus provides insights into how sequence and genomic SVs control agronomic traits of NIP and 93-11; it also provides genome-editing targets for molecular breeding aiming at improving favorable agronomic properties.
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Oryza , Oryza/genética , Cromatina/genética , Estudo de Associação Genômica Ampla , Epigênese Genética , Elementos de DNA Transponíveis/genética , Genômica , Genoma de Planta/genéticaRESUMO
The biological implications of R-loops are increasingly receiving attention in plant biology. Compared with recent progresses in humans, the studies of R-loops in plants are lagging behind. Massive efforts must be invested by the plant community to better harness the possible regulatory functions of R-loops. Pioneering studies indicate that R-loops might act as key regulators of plant growth and development, and stress responses. This review thus timely updates the biological implications of R-loops and proposes a series of future lines of investigations to further decipher R-loop biology in plants. The following three aspects are included: the interplay between R-loops and epigenetic modifications at DNA, RNA, and chromatin levels; their regulatory roles in genome integrity, centromere functions, and DNA replication; and how they likely control plant growth and development as well as stress responses and RNA processing. Altogether, the wealth of information provided here portrays R-loop biology in plants accurately, and makes these new regulators interesting genetic levers in developing plants with new and beneficial agronomical traits.
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Agricultura , Estruturas R-Loop , Humanos , Centrômero , Cromatina , Epigênese GenéticaRESUMO
Underground landfill, the primary disposal method of construction waste in several areas, negatively affects the surrounding environments. Suitably locating and estimating waste volume in an underground landfill are vital for adequate disposal and recycling of construction wastes. In this study, we investigated the applicability of ground penetrating radar (GPR) technology to estimate waste depth and volume of a construction waste landfill. The results revealed the following. (1) The GPR technology effectively delineated boundaries between underground waste and the surrounding strata; the topographic structure obtained from the analysis of the associated images was consistent with the actual topography. (2) Layer information from GPR images and electromagnetic wave velocity calculated using the complex refractive index model for construction waste burial depth inversion produced highly accurate results. Waste depth in the landfill was estimated using the GPR inversion results and spatial interpolation. Kriging interpolation exhibited the highest accuracy. (3) The trapezoid, Simpson and Simpson 3/8 rules were suitable for estimating construction waste volume. A three-dimensional model created using the spatial interpolation grid precisely depicted the structure of the buried landfill. Our study provides references for the management, recycling and environmental impact assessment of construction waste.
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The elucidation of epigenetic responses of salt-responsive genes facilitates understanding of the underlying mechanisms that confer salt tolerance in rice. However, it is still largely unknown how epigenetic mechanisms are associated with the expression of salt-responsive genes in rice and other crops. In this study, we reported tissue-specific gene expression and tissue-specific changes in chromatin modifications or signatures between seedlings and roots in response to salt treatment. Our study indicated that among six of individual mark examined (H3K4me3, H3K27me3, H4K12ac, H3K9ac, H3K27ac and H3K36me3), a positive association between salt-related changes in histone marks and the expression of differentially expressed genes (DEGs) was observed only for H3K9ac and H4K12ac in seedlings and H3K36me3 in roots. In contrast, chromatin states (CSs) with combinations of six histone modification marks played crucial roles in the differential expression of salt-responsive genes between seedlings and roots. Most importantly, CS7 containing the bivalent marks H3K4me3 and H3K27me3, with a mutual exclusion of functions with each other, displayed distinct functions in the expression of DEGs in both tissues. Specifically, H3K27me3 in CS7 mainly suppressed the expression of DEGs in roots, while H3K4me3 affected the expression of down- and up-regulated genes, possibly by antagonizing the repressive role of H3K27me3 in seedlings. Our findings indicate distinct impacts of the CSs on the differential expression of salt-responsive genes between seedlings and roots in rice, which provides an important background for understanding chromatin-based epigenetic mechanisms that might confer salt tolerance in plants.
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Cromatina/metabolismo , Oryza/metabolismo , Raízes de Plantas/metabolismo , Plântula/metabolismo , Divisão Celular/genética , Divisão Celular/fisiologia , Regulação da Expressão Gênica de Plantas , Oryza/genética , Peroxirredoxinas/genética , Peroxirredoxinas/metabolismo , Fotossíntese/genética , Fotossíntese/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Plântula/genéticaRESUMO
BACKGROUND: The role of histone modifications in the DNA damage response has been extensively studied in non-plant systems, including mammals and yeast. However, there is a lack of detailed evidence showing how chromatin dynamics, either an individual mark or combined chromatin states, participate in regulating differentially expressed genes in the plant DNA damage response. RESULTS: In this study, we used RNA-seq and ChIP-seq to show that differentially expressed genes (DEGs), in response to ionizing radiation (IR), might be involved in different pathways responsible for the DNA damage response. Moreover, chromatin structures associated with promoters, exons and intergenic regions are significantly affected by IR. Most importantly, either an individual mark or a certain chromatin state was found to be highly correlated with the expression of up-regulated genes. In contrast, only the chromatin states, as opposed to any individual marks tested, are related to the expression of the down-regulated genes. CONCLUSIONS: Our findings demonstrate that IR-related DEGs are modulated by distinct epigenetic mechanisms. Either chromatin states or distinct histone dynamics may act sequentially or in combination in regulating up-regulated genes, but the complex chromatin structure is mainly responsible for the expression of down-regulated genes. Thus, this study provides new insights into how up- and down-regulated genes are epigenetically regulated at the chromatin levels, thereby helping us to understand distinct epigenetic mechanisms that function in the plant DNA damage response.
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Cromatina/genética , Cromatina/efeitos da radiação , Radioisótopos de Cobalto/farmacologia , Raios gama , Oryza/genética , Oryza/efeitos da radiação , Transcriptoma/efeitos da radiação , Dano ao DNA , Éxons/genética , Histonas/metabolismo , Análise de Sequência de RNA , Transcrição Gênica/efeitos da radiaçãoRESUMO
Based on the PM2.5 concentration and meteorological data of "2+26" cities, the variations in PM2.5 time series were analyzed by the continuous wavelet transform(CWT) and discrete wavelet transform(DWT). Wavelet coherence(WTC) and multiple wavelet coherence(MWC) were used to quantify the response relationship between PM2.5 and single/multiple meteorological factors in the time-frequency domain. Partial wavelet coherence(PWC) was used to quantitatively evaluate the influence of atmospheric teleconnection factors on the response relationship. The results showed that:â the concentration of PM2.5 in the "2+26" cities had the spatial distribution characteristics of high in the middle area and low in the peripheral area. The PM2.5 mutation events were mainly concentrated before 2018 and mostly occurred in winter when the meteorological conditions were stable. The annual scale period of 256-512 d was relatively stable, and it was also the dominant period of the PM2.5 time series. â¡ The coherences between PM2.5 and meteorological factors depended on the time-frequency scale and variable combination. At all time-frequency scales, PM2.5 had strong coherences with relative humidity and temperature. At small and medium time-frequency scales, PM2.5 had strong coherences with wind speed. At large scales, PM2.5 had strong coherences with temperature. The combination of precipitation, temperature, and relative humidity could explain the variation in PM2.5 at all time-frequency scales. ⢠At different time-frequency scales, the enhancement/weakening effects of atmospheric teleconnection factors on the response relationship were not the same. At all time-frequency scales, the El Niño-Southern Oscillation(ENSO) had a greater impact on the response relationship between PM2.5 and precipitation/temperature, and the Pacific decadal oscillation(PDO) had a greater impact on the response relationship between PM2.5 and relative humidity/wind speed. These results provide reference for regional air pollution control.
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Bacterial has become a common pathogen of humans owing to their drug-resistant effects and evasion of the host immune system, with their ability to form biofilm and induce severe infections, a condition which has become a primary public health concern globally. Herein, we report on CuO@AgO/ZnO NPs antibacterial activity enhanced by near-infrared (NIR) light which was effective in the elimination of Staphylococcus aureus and the Pseudomonas aeruginosa. The CuO@AgO/ZnO NPs under NIR significantly eradicated S. aureus and its biofilm and P. aeruginosa in vitro, and subsequently exhibited such phenomenon in vivo, eliminating bacteria and healing wound. This demonstrated the combined intrinsic antibacterial potency of the Cu and Ag components of the CuO@AgO/ZnO NPs was enhanced tremendously to achieve such outcomes in vitro and in vivo. Considering the above advantages and facile preparation methods, the CuO@AgO/ZnO NPs synthesized in this work may prove as an important antibacterial agent in bacterial-related infection therapeutics and for biomedical-related purposes.
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OBJECTIVES: This study aims to investigate the cytotoxicity and sustainable antibacterial activity of unmodified PEEK under specific wavelength light treatment (365 nm), and its antibacterial mechanism was also preliminarily discussed. METHODS: A near-ultraviolet source with a wavelength of 365 nm and a power of 5 W were selected. The irradiation time was 30 min, and the distance was 100 mm. A water contact angle tester was used to characterize the surface of the PEEK after 1-15 light treatments. MC3TC-E1 cells were used to evaluate the cytotoxicity of the materials under light treatment. Five kinds of common oral bacteria were detected in vitro, and antibacterial efficiency was determined by colony-forming unit (CFU) and scanning electron microscope (SEM). The antibacterial mechanism of PEEK under light was preliminarily discussed by spectrophotometry. The membrane rupture of Staphylococcus aureus and Escherichia coli was detected by lactate dehydrogenase. Staphylococcus aureus and Staphylococcus mutans were selected for the cyclic antibacterial test. Statistical analysis was performed by one-way analysis of variance and Tukey multiple range test. A significance level of 0.05 was considered (α = 0.05). RESULTS: The results of the cell experiment showed that PEEK had no cytotoxicity (P > 0.05). CFU results showed that PEEK had an obvious antibacterial effect on Staphylococcus aureus, Staphylococcus mutans, Staphylococcus gordonii and Staphylococcus sanguis, but had no antibacterial effect on Escherichia coli (P < 0.05). The SEM results also verified the above antibacterial effect. The existence of singlet oxygen was confirmed by spectrophotometry. Meanwhile, the rupture of Staphylococcus aureus membrane was verified by lactate dehydrogenase assay. The water contact angle of the PEEK surface did not change significantly after 15 cycles of light treatment. Cyclic antibacterial experiments showed that the antibacterial effect was sustainable. CONCLUSIONS: This study showed that PEEK has good cytocompatibility with stable and sustainable antibacterial properties under near-ultraviolet. It provides a new idea to solve the non-antibacterial property of PEEK, and also provides a theoretical basis for its further application in dentistry.
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Cetonas , Polietilenoglicóis , Polietilenoglicóis/farmacologia , Cetonas/farmacologia , Benzofenonas/farmacologia , Staphylococcus aureus , Antibacterianos/farmacologia , Escherichia coli , Água , Lactato Desidrogenases , ÉteresRESUMO
XG Chinese kale (Brassica oleracea cv. 'XiangGu') is a variety of Chinese kale and has metamorphic leaves attached to the true leaves. Metamorphic leaves are secondary leaves emerging from the veins of true leaves. However, it remains unknown how the formation of metamorphic leaves is regulated and whether it differs from normal leaves. BoTCP25 is differentially expressed in different parts of XG leaves and respond to auxin signals. To clarify the function of BoTCP25 in XG Chinese kale leaves, we overexpressed BoTCP25 in XG and Arabidopsis, and interestingly, its overexpression caused Chinese kale leaves to curl and changed the location of metamorphic leaves, whereas heterologous expression of BoTCP25 in Arabidopsis did not show metamorphic leaves, but only an increase in leaf number and leaf area. Further analysis of the expression of related genes in Chinese kale and Arabidopsis overexpressing BoTCP25 revealed that BoTCP25 could directly bind the promoter of BoNGA3, a transcription factor related to leaf development, and induce a significant expression of BoNGA3 in transgenic Chinese kale plants, whereas this induction of NGA3 did not occur in transgenic Arabidopsis. This suggests that the regulation of Chinese kale metamorphic leaves by BoTCP25 is dependent on a regulatory pathway or elements specific to XG and that this regulatory element may be repressed or absent from Arabidopsis. In addition, the expression of miR319's precursor, a negative regulator of BoTCP25, also differed in transgenic Chinese kale and Arabidopsis. miR319's transcrips were significantly up-regulated in transgenic Chinese kale mature leaves, while in transgenic Arabidopsis, the expression of miR319 in mature leaves was kept low. In conclusion, the differential expression of BoNGA3 and miR319 in the two species may be related to the exertion of BoTCP25 function, thus partially contributing to the differences in leaf phenotypes between overexpressed BoTCP25 in Arabidopsis and Chinese kale.
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The availability of multiple wheat genome sequences enables us to identify core genes and characterize their genetic and epigenetic features, thereby advancing our understanding of their biological implications within individual plant species. It is, however, largely understudied in wheat. To this end, we reanalyzed genome sequences from 16 different wheat varieties and identified 62,299 core genes. We found that core and non-core genes have different roles in subgenome differentiation. Meanwhile, according to their expression profiles, these core genes can be classified into genes related to tissue development and stress responses, including 3376 genes highly expressed in both spikelets and at high temperatures. After associating with six histone marks and open chromatin, we found that these core genes can be divided into eight sub-clusters with distinct epigenomic features. Furthermore, we found that ca. 51% of the expressed transcription factors (TFs) were marked with both H3K27me3 and H3K4me3, indicative of the bivalency feature, which can be involved in tissue development through the TF-centered regulatory network. Thus, our study provides a valuable resource for the functional characterization of core genes in stress responses and tissue development in wheat.
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Epigenômica , Triticum , Epigênese Genética , Regulação da Expressão Gênica de Plantas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Triticum/genética , Triticum/metabolismoRESUMO
To overcome the limitations of traditional therapeutics, nanotechnology offers a synergistic therapeutic approach for the treatment of bacterial infection and biofilms that has attracted attention. Herein, we report on a ZnO@Ag nanocomposite with good biocompatibility synthesized by doping ZnO NPs with silver nanoparticles (Ag NPs). ZnO@Ag nanocomposites were synthesized with varying ratios of Ag NPs (0.5%, 2%, 8%). Under the same experimental conditions, ZnO@8%Ag exhibited outstanding properties compared to the other nanocomposites and the pristine ZnO NPs. ZnO@8%Ag demonstrated excellent photothermal and photodynamic properties. Also, ZnO@8%Ag demonstrated over 99% inhibition of Staphylococcus aureus (S. aureus) under photothermal therapy (PTT) or photodynamics therapy (PDT) as a result of the excessive generation of reactive oxygen species (ROS) by the Ag+ released, while the pristine ZnO showed an insignificant inhibition rate compared to the PBS group (control). Furthermore, ZnO@8%Ag completely disrupted S. aureus biofilm under a combined PTT/PDT treatment, a synergetic trimodal therapy, although the molecular mechanism of biofilm inhibition remains unclear. Hence, the excellent photothermal, photodynamic, biocompatibility, and bactericidal properties of ZnO@8%Ag present it as an appropriate platform for bacterial and biofilm treatment or other biomedically related applications.
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In this study, a large construction waste dump in Beijing, China, was used as the study area. Nineteen effective atmospheric dust samples were collected. The mass fractions of 14 metal elements (Ca, Fe, Al, Mg, Mn, Zn, Cr, Cu, V, Pb, Ni, As, Co, and Cd) were determined for the samples using ICP-MS. The pollutants and the potential ecological risk levels of 10 different heavy metals were evaluated using the enrichment factor, geo-accumulation index, and a potential ecological risk assessment method. The results showed that the Ca, Fe, Al, and Mg contents in the dust fall were considerably high and accounted for 98.81% of the total mass of the analysed metals. Cd and Zn were the main metal contaminants in the dust fall in the vicinity of the construction waste dump, followed by Cu and Mn. The Cd, Zn, Cu, and Mn contents in the construction waste had a significant impact on atmospheric pollution within 250 m of the dump. Moreover, Cd had the largest contribution to the comprehensive ecological risk posed by the heavy metals in the dust fall and was determined to be the primary ecological risk factor in the atmospheric environment in the vicinity of the construction waste dump.
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Poluentes Ambientais , Metais Pesados , Poeira/análise , Pequim , Monitoramento Ambiental/métodos , Cádmio/análise , Chumbo/análise , Metais Pesados/análise , Medição de Risco , Instalações de Eliminação de Resíduos , China , Poluentes Ambientais/análiseRESUMO
OBJECTIVE: Lung cancer (LC) remains a threatening health issue worldwide. Methyltransferase-like protein 3 (METTL3) is imperative in carcinogenesis via m6A modification of microRNAs (miRNAs). This study estimated the effect of METTL3 in LC by regulating m6A methylation-mediated pri-miR-663 processing. METHODS: miR-663 expression in 4 LC cell lines and normal HBE cells was determined using RT-qPCR. A549 and PC9 LC cells selected for in vitro studies were transfected with miR-663 mimics or inhibitor. Cell viability, migration, invasion, proliferation, and apoptosis were detected by CCK-8, Transwell, EdU, and flow cytometry assays. The downstream target genes and binding sites of miR-663 were predicted via Starbase database and validated by dual-luciferase assay. LC cells were delivered with oe-METTL3/sh-METTL3. Crosslinking between METTL3 and DGCR8 was verified by co-immunoprecipitation. Levels of m6A, miR-663, and pri-miR-663 were measured by m6A dot blot assay and RT-qPCR. m6A modification of pri-miR-663 was verified by Me-RIP assay. Finally, the effects of METTL3 in vivo were ascertained by tumor xenograft in nude mice. RESULTS: miR-663 was upregulated in LC cells, and miR-663 overexpression promoted cell proliferation, migration, invasion, and inhibited apoptosis, but miR-663 knockdown exerted the opposite effects. miR-663 repressed SOCS6 expression. SOCS6 overexpression annulled the promotion of miR-663 on LC cell growth. METTL3 bound to DGCR8, and METTL3 silencing elevated the levels of pri-miR-663 and m6A methylation-modified pri-miR-663, and suppressed miR-663 maturation and miR-663 expression. METTL3 facilitated tumor growth in mice through the miR-663/SOCS6 axis. CONCLUSION: METTL3 promotes LC progression by accelerating m6A methylation-mediated pri-miR-663 processing and repressing SOCS6.
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Neoplasias Pulmonares , MicroRNAs , Humanos , Animais , Camundongos , Metiltransferases/genética , Metiltransferases/metabolismo , Metilação , MicroRNAs/genética , MicroRNAs/metabolismo , Camundongos Nus , Sincalida/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias Pulmonares/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismoRESUMO
Extreme heat caused by global climate change has become a serious threat to the sustainable development of urban areas. Scientific assessment of the impacts of extreme heat on urban areas and in-depth knowledge of the cross-scale mechanisms of heat vulnerability forming in urban systems are expected to support policymakers and stakeholders in developing effective policies to mitigate the economic, social, and health risks. Based on the perspective of the human-environment system, this study constructed a conceptual framework and index system of "exposure-susceptibility-adaptive capacity" for urban heat vulnerability (UHV) and proposed its assessment methods. Taking Xiamen City, a coastal metropolis, as an example, spatial analysis and Geodetector were used to explore the spatial and temporal changes, spatial characteristics, and patterns of UHV under multiple external disturbances from natural to anthropological factors, and to reveal the main factors influencing UHV forming and spatial differentiation. Results showed that the exposure, susceptibility, adaptive capacity, and UHV in Xiamen City had a spatial structure of "coastal-offshore-inland". On the hot day, both the exposure and UHV showed a temporal pattern of "rising and then falling, peaking at 14:00" and a spatial pattern of "monsoonal-like" movement between coast and inland. Coastal zoning with favorable socioeconomic conditions had less magnitude of changes in UHV, where the stability of the urban system was more likely to be maintained. During the hot months, the high UHV areas were mainly distributed in the inland, while coastal areas showed low UHV levels. Further, coastal UHV was mainly dominated by "heat exposure", offshore by "comprehensive factors", and inland in the northern mountainous areas by "lack of adaptive capacity". Multi-scale urban adaptive capacity was confirmed to alter spatial distribution of exposure and reshape the spatial pattern of UHV. This study promotes the application of multi-scale vulnerability framework to disaster impact assessment, enriches the scientific knowledge of the urban system vulnerability, and provides scientific references for local targeted cooling policy development and extreme heat resilience building programs.
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Mudança Climática , Temperatura Alta , Humanos , Cidades , ChinaRESUMO
Equipped with anti-oxidative properties, cerium oxide nanoparticles (CNPs) are gradually being adopted over the years in the field of oxidative stress research. However, the effects of CNPs may be diminished when under the influence of prolonged and substantially elevated levels of oxidative stress. Therefore, it is imperative to enhance the efficacy of CNPs to resist oxidative stress. In this study, our approach involves the fabrication of titanium surface CNPs coatings doped with different concentrations of lanthanum ions (La3+) and the investigation of their local anti-oxidative stress potential. The physicochemical characterization showed that the La-CNPs groups had a substantial increase in the generation of oxygen vacancies within the CNPs structure with the increase of La doping concentration. In vitro findings proofed that the cytocompatibility of different La-CNPs coatings showed a trend of increasing first and then decreasing with the increase of La doping concentration under oxidative stress microenvironment. Among these groups, the 30 % La-CNPs group presented the best cell proliferation and osteogenic differentiation which could activate the FoxO1 pathway, then upregulated the expression of SOD1 and CAT, and finally resulted in the inhibition of ROS production. In vivo results further confirmed that the 30 % La-CNPs group showed significant osteogenic effects in two rat models (osteoporosis and diabetes models). In conclusion, we believe that the 30 % La-CNPs coating holds promising potential for its implant applications in patients with oxidative stress-related diseases.
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Cério , Implantes Dentários , Nanopartículas , Animais , Cério/química , Cério/farmacologia , Lantânio/farmacologia , Nanopartículas/química , Osteogênese , Ratos , Espécies Reativas de Oxigênio/metabolismo , Titânio/farmacologiaRESUMO
Cotton is an excellent model for studying crop polyploidization and domestication. Chromatin profiling helps to reveal how histone modifications are involved in controlling differential gene expression between A and D subgenomes in allotetraploid cotton. However, the detailed profiling and functional characterization of broad H3K4me3 and H3K27me3 are still understudied in cotton. In this study, we conducted H3K4me3- and H3K27me3-related ChIP-seq followed by comprehensively characterizing their roles in regulating gene transcription in cotton. We found that H3K4me3 and H3K27me3 exhibited active and repressive roles in regulating the expression of genes between A and D subgenomes, respectively. More importantly, H3K4me3 exhibited enrichment level-, position-, and distance-related impacts on expression levels of related genes. Distinct GO term enrichment occurred between A/D-specific and homeologous genes with broad H3K4me3 enrichment in promoters and gene bodies, suggesting that broad H3K4me3-marked genes might have some unique biological functions between A and D subgenome. An anticorrelation between H3K27me3 enrichment and expression levels of homeologous genes was more pronounced in the A subgenome relative to the D subgenome, reflecting distinct enrichment of H3K27me3 in homeologous genes between A and D subgenome. In addition, H3K4me3 and H3K27me3 marks can indirectly influence gene expression through regulatory networks with TF mediation. Thus, our study provides detailed insights into functions of H3K4me3 and H3K27me3 in regulating differential gene expression and subfunctionalization of homeologous genes, therefore serving as a driving force for polyploidization and domestication in cotton.
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BACKGROUND: The purpose of the current meta-analysis was to compare the oncological outcomes of pemetrexed versus gefitinib in pre-treated advanced or metastatic non-small cell lung cancer (NSCLC) patients. METHODS: Search the online electronic databases on comparison the effectiveness and adverse effects of pemetrexed versus gefitinib in therapy outcomes of pre-treated NSCLC to September 2019. All studies analyzed the summary odds ratios (ORs) of the main outcomes, including survival efficacy and toxicity complications. RESULTS: In all, 5 trials involving 676 subjects were included, with 332 receiving pemetrexed and 344 using gefitinib. The pooled analysis of overall survival (OS) (ORâ=â0.97, 95%CIâ=â0.77-1.21, Pâ=â.76) and progression-free survival (PFS) (ORâ=â1.17, 95%CIâ=â0.60-2.30, Pâ=â.65) showed that pemetrexed did not achieve benefit when compared with gefitinib. In the results of subgroup analysis among the EGFR mutation-positive patients, the comparison of gefitinib therapy versus pemetrexed did show PFS benefit 0.35 (95%CI 0.12-1.01; Pâ=â.05). In terms of grade 3 or 4 side effects, a similar toxicity profile of both pemetrexed and gefitinib was shown in the incidence rate of rash (Pâ=â.045), fatigue (Pâ=â.97), thrombocytopenia (Pâ=â.68) and anemia (Pâ=â.21) between the 2 groups. CONCLUSION: Pemetrexed was not associated with survival benefit than gefitinib therapy among pre-treated NSCLC patients. While, gefitinib showed superior PFS efficacy than pemetrexed for patients with EGFR mutation-type. Future investigations are required to identify relevant biomarkers in selected patients that would most likely benefit from pemetrexed or gefitinib treatment in pre-treated advanced NSCLC patients.