The influence of high temperature repressing treatment on the segregation of phosphorus in the 93W alloy was carefully investigated by means of Auger electron spectroscope,EPMA, TEM and SEM.The segregation of phosphor...The influence of high temperature repressing treatment on the segregation of phosphorus in the 93W alloy was carefully investigated by means of Auger electron spectroscope,EPMA, TEM and SEM.The segregation of phosphorus has been observed at the tungsten-tungsten grain boundaries,particularly at the tungsten-matrix interphases when the specimens were kept at the temperature in the range of 1200—1500℃ ,followed by furnace cooling.However, no segregation of phosphorus was observed at the interfaces after the specimens were re- pressed at the range of temperature,followed by furnace cooling.After investigation,the dis- locations in the matrix phase of as-repressed specimens directly influenced the phosphorus segregation to the interfaces.After annealing,the mechanical properties were reduced because of the phosphorus segregation at the interface boundaries.展开更多
Increasing density is one of the important factors for producing high quality powder metallurgy （PM） parts, which has beneficial effect on mechanical properties. One of the common techniques for achieving this goal ...Increasing density is one of the important factors for producing high quality powder metallurgy （PM） parts, which has beneficial effect on mechanical properties. One of the common techniques for achieving this goal is double compacting, which seems to be a potentially attractive method in PM route, also for Cr-Mo alloyed-steels. The objective of this research was to investigate the effect of first compacting pressure and intermediate annealing temperature on attaining higher densities and minimum interconnected porosity for Cr-Mo pre-alloyed steel. The effect of mentioned parameters was studied by measuring density, transverse rupture strength and macrohardness of repressed samples. The results show that for each first compacting pressure, the density range of repressed samples increases with the increasing annealing temperature up to a certain limit, due to C dissolution which causes free porosity and further densifieation. Annealing temperatures higher than optimum one should be avoided, since too much carbon dissolution results in harder and less deformable compacts. On the other hand, with regard to repressed density and other resulted properties, the amount of first compacting pressure offers considerable advantage in obtaining higher level of density and consequently improved mechanical properties.展开更多
Aiming at the corrosion issue of oil extraction equipments caused by sulfate-reducing bacteria （SRB） reproducing in oil field affusion system, we studied the dominant strains in the SRB community and the impact of f...Aiming at the corrosion issue of oil extraction equipments caused by sulfate-reducing bacteria （SRB） reproducing in oil field affusion system, we studied the dominant strains in the SRB community and the impact of four ecological factors on the growth of the dominant strains：temperature, pH, mineralization degree and concentration of PAM （Polyacrylamine）. The feasibility of repressing the growth of SRB by changing ecological factors was also discussed. The results indicate that Desutfobacter （one genus of SRB） is the preponderant strains of the system, and the order of the effect of four ecological factors is pH 〉 temperature 〉 the concentrations of PAM 〉 mineralization degree. The optimal pH for the highest growth rate of SRB is 8.0. No growth of SRB was observed when pH 〈 4 or pH 〉 12. The optimal temperature for the growth of SRB is 40 ℃ and the ecological amplitude is 20 -50 ℃. The appropriate concentration values of PAM is 400 -800 mg/L, beyond of which the multiplication rate and growth quantity 6f cell decrease obviously. The effect of mineralization degree of SO4^2- , HCO^3- and Na^＋ on the growth of SRB has reached an extremely remarkable level, and the change of three ions＇ concentration in water obviously effects SRB： The optimum values on the main ions in the system are Cl- of 200mg/L, HCO^3- of 900 mg/L,SO4^2- of 400 mg/L, Mg^2＋ of 60 mg/L and Na^＋ of 900 mg/L. Our results indicate that it is possible to repress the growth of SRB by changing the ecological factors in nil field affusion system.展开更多
Neural activities differentiating bodies versus non-body stimuli have been identified in the occipitotemporal cortex of both humans and nonhuman primates.However,the neural mechanisms of coding the similarity of diffe...Neural activities differentiating bodies versus non-body stimuli have been identified in the occipitotemporal cortex of both humans and nonhuman primates.However,the neural mechanisms of coding the similarity of different individuals’bodies of the same species to support their categorical representations remain unclear.Using electroencephalography(EEG)and magnetoencephalography(MEG),we investigated the temporal and spatial characteristics of neural processes shared by different individual body silhouettes of the same species by quantifying the repetition suppression of neural responses to human and animal(chimpanzee,dog,and bird)body silhouettes showing different postures.Our EEG results revealed significant repetition suppression of the amplitudes of early frontal/central activity at 180–220 ms(P2)and late occipitoparietal activity at 220–320 ms(P270)in response to animal(but not human)body silhouettes of the same species.Our MEG results further localized the repetition suppression effect related to animal body silhouettes in the left supramarginal gyrus and left frontal cortex at 200–440 ms after stimulus onset.Our findings suggest two neural processes that are involved in spontaneous categorical representations of animal body silhouettes as a cognitive basis of human-animal interactions.展开更多
Background:Globally,breast cancer constitutes the predominant malignancy in women.Abnormal regulation of epigenetic factors plays a key role in the development of tumors.Anti-apoptosis is a characteristic of tumor cel...Background:Globally,breast cancer constitutes the predominant malignancy in women.Abnormal regulation of epigenetic factors plays a key role in the development of tumors.Anti-apoptosis is a characteristic of tumor cells.Therefore,exploring and identifying relevant epigenetic factors that regulate the apoptosis of tumor cells is the foundation for clarifying the pathogenesis of tumors and achieving precision antitumor therapy.Method:This study focused on exploring the epigenetic mechanism of FOXK1 in the development of estrogen receptor-positive(ER^(+))breast cancer.We used overexpressing FLAG-FOXK1 MCF-7 cells to perform silver staining mass spectrometry analysis and conducted Co-IP experiments to verify the interactions.ChIP-seq was conducted on MCF-7 cells to examine FOXK1's binding across the genome and its transcriptional target sites.To validate the ChIP-seq results,qChIP,western blotting,and quantitative polymerase chain reaction(qPCR)were performed.Through TUNEL assay,cell counting assay,colony formation assay,and the mouse xenograft models,the effect of FOXK1 on breast cancer progression was detected.Finally,by analyzing online databases,the correlation between FOXK1 and the survival of breast cancer patients was examined.Results:FOXK1 interacts with the REST/CoREST transcriptional corepression complex to transcriptionally inhibit target genes representing the apoptotic pathway.Abnormally high expression of FOXK1 prevents the apoptosis of ER+breast cancer cells in vitro and promotes ER+breast tumor progression in vivo.Furthermore,the expression of FOXK1 is negatively correlated with the survival of ER+breast cancer patients.Conclusion:FOXK1 promotes ER+breast carcinogenesis through anti-apoptosis and acts as a potential target for ER+breast cancer treatment.展开更多
Toll-like receptors (TLRs) play critical roles in innate immunity and inflammation. The molecular mechanisms by which TLR signaling is fine-tuned remain to be completely elucidated. Cullin 4B (CUL4B), which assembles ...Toll-like receptors (TLRs) play critical roles in innate immunity and inflammation. The molecular mechanisms by which TLR signaling is fine-tuned remain to be completely elucidated. Cullin 4B (CUL4B), which assembles the CUL4B-RING E3 ligase complex (CRL4B), has been shown to regulate diverse developmental and physiological processes by catalyzing monoubiquitination for histone modification or polyubiquitination for proteasomal degradation. Here, we identified the role of CUL4B as an intrinsic negative regulator of the TLR-triggered inflammatory response. Deletion of CUL4B in macrophages increased the production of proinflammatory cytokines and decreased anti-inflammatory cytokine IL-10 production in response to pathogens that activate TLR3, TLR4, or TLR2. Myeloid cell-specific Cul4b knockout mice were more susceptible to septic shock when challenged with lipopolysaccharide, polyinosinic-polycytidylic acid or Salmonella typhimurium infection. We further demonstrated that enhanced TLR-induced inflammatory responses in the absence of CUL4B were mediated by increased GSK3β activity. Suppression of GSK3β activity efficiently blocked the TLR-triggered increase in proinflammatory cytokine production and attenuated TLR-triggered death in Cul4b mutant mice. Mechanistically, CUL4B was found to negatively regulate TLR-triggered signaling by epigenetically repressing the transcription of Pten, thus maintaining the anti-inflammatory PI3K-AKT-GSK3β pathway. The upregulation of PTEN caused by CUL4B deletion led to uncontrolled GSK3β activity and excessive inflammatory immune responses. Thus, our findings indicate that CUL4B functions to restrict TLR-triggered inflammatory responses through regulating the AKT-GSK3β pathway.展开更多
The rice false smut disease, caused by Ustilaginoidea virens, has emerged as a significantglobal threat to rice production. The mechanism of carbon catabolite repression plays a crucial role in theefficient utilizatio...The rice false smut disease, caused by Ustilaginoidea virens, has emerged as a significantglobal threat to rice production. The mechanism of carbon catabolite repression plays a crucial role in theefficient utilization of carbon nutrients and enzyme regulation in the presence of complex nutritionalconditions. Although significant progress has been made in understanding carbon catabolite repression infungi such as Aspergillus nidulans and Magnaporthe oryzae, its role in U. virens remains unclear. Toaddress this knowledge gap, we identified UvCreA, a pivotal component of carbon catabolite repression,in U. virens. Our investigation revealed that UvCreA localized to the nucleus. Deletion of UvCreA resultedin decreased growth and pathogenicity in U. virens. Through RNA-seq analysis, it was found that theknockout of UvCreA led to the up-regulation of 514 genes and down-regulation of 640 genes. Moreover,UvCreA was found to be involved in the transcriptional regulation of pathogenic genes and genesassociated with carbon metabolism in U. virens. In summary, our findings indicated that UvCreA isimportant in fungal development, virulence, and the utilization of carbon sources through transcriptionalregulation, thus making it a critical element of carbon catabolite repression.展开更多
The specification of germ cells in zebrafish mostly relies on an inherited mechanism by which localized maternal determinants,called germ plasm,confer germline fate in the early embryo.Extensive studies have partially...The specification of germ cells in zebrafish mostly relies on an inherited mechanism by which localized maternal determinants,called germ plasm,confer germline fate in the early embryo.Extensive studies have partially allowed the identification of key regulators governing germ plasm formation and subsequent germ cell development.RNA-binding proteins,acting in concert with other germ plasm components,play essential roles in the organization of the germ plasm and the specification,migration,maintenance,and differentiation of primordial germ cells.The loss of their functions impairs germ cell formation and causes sterility or sexual conversion.Evidence is emerging that they instruct germline development through differential regulation of mRNA fates in somatic and germ cells.However,the challenge remains to decipher the complex interplay of maternal germ plasm components in germ plasm compartmentalization and germ cell specification.Because failure to control the developmental outcome of germ cells disrupts the formation of gametes,it is important to gain a complete picture of regulatory mechanisms operating in the germ cell lineage.This review sheds light on the contributions of RNA-binding proteins to germ cell development in zebrafish and highlights intriguing questions that remain open for future investigation.展开更多
Long non-coding RNA (lncRNA) refers to an over 200 nt functional RNA molecule that will not be translated into protein. Previously thought to be dark matters of the genome, lncRNAs have been gradually recognized as cr...Long non-coding RNA (lncRNA) refers to an over 200 nt functional RNA molecule that will not be translated into protein. Previously thought to be dark matters of the genome, lncRNAs have been gradually recognized as crucial gene regulators. Although tremendous progress has been made in animals and human, the study of lncRNAs in plant is still in its infancy. Here, we reviewed the biogenesis and regulation mechanisms of lncRNAs and summarized the achievements that have been made in plant lncRNA identification and functional characterization. Genome-wide identification has uncovered large amount of lncRNAs in Arabidopsis, Rice, Maize and Wheat, and more information from other plant species will be expected with the aid of deep sequencing technologies. Similar to other species, LncRNA-mediated gene regulation also widely exists in plants, even though only a few functionally characterized examples are available. Up to now, at least four divergent lncRNA-mediated regulation mechanisms have been unraveled, including target mimicry, transcription interference, PRC2 associated histone methylation and DNA methylation. lncRNAs may be involved in the regulation of flowering, male sterility, nutrition metabolism, biotic and abiotic stress response in plants.展开更多
Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcri...Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcription may be regulated epigenetically. Using a custom-designed microarray, here we examine the expression profile of IncRNAs in embryonic stem （ES） cells, lineage-restricted neuronal progenitor cells, and terminally differentiated fibroblasts. In addition, we also analyze the relationship between their expression and their promoter H3K4 and H3K27 methyla- tion patterns. We find that numerous lncRNAs in these cell types undergo changes in the levels of expression and promoter H3K4me3 and H3K27me3. Interestingly, lncRNAs that are expressed at lower levels in ES cells exhibit higher levels of H3K27me3 at their promoters. Consistent with this result, knockdown of the H3K27me3 methyltransferase Ezh2 results in derepression of these IncRNAs in ES cells. Thus, our results establish a role for Ezh2-mediated H3K27 methylation in lncRNA silencing in ES cells and reveal that lncRNAs are subject to epigenetic regulation in a similar manner to that of the protein-coding genes.展开更多
Polycomb group （PCG） complexes are epigenetic regulatory complexes that conduct transcriptional repression of target genes via modifying the chromatin. The two best characterized forms of PCG complexes, polycomb rep...Polycomb group （PCG） complexes are epigenetic regulatory complexes that conduct transcriptional repression of target genes via modifying the chromatin. The two best characterized forms of PCG complexes, polycomb repressive complexes 1 and 2 （PRC1 and PRC2）, are required for maintaining the sternness of embryonic stem cells and many types of adult stem cells. The spectra of target genes for PRCs are dynamically changing with cell differentiation, which is essential for proper decisions on cell fate during developmental processes, Chromobox （CBX） family proteins are canonical components in PRC1, responsible for targeting PRC1 to the chromatin. Recent studies highlight the function specifications among CBX family members in undifferentiated and differentiated stem cells, which reveal the interplay between compositional diversity and functional specificity of PRCI. In this review, we summarize the current knowledge about targeting and functional mechanisms of PRCs, emphasizing the recent breakthroughs related to CBX proteins under a number of physiological and pathological conditions.展开更多
Over the past decades,tRNA was found to be a rich hub of RNA modifications such as 1-methyladenosine and 5-methycytosine modifications and others,holding more than half of all modifications occurring in RNA molecules....Over the past decades,tRNA was found to be a rich hub of RNA modifications such as 1-methyladenosine and 5-methycytosine modifications and others,holding more than half of all modifications occurring in RNA molecules.Moreover,tRNA was discovered to be a source of various small noncoding RNA species,such as the stress induced angiogenin cleaved tRNA halves(tiRNA)or the miRNA like tRNA derived fragments.tRNA cleavage under stress was fist discovered in bacteria and later was found to be conserved across different species,including mammals.Under cellular stress conditions,tRNA undergoes conformational changes and angiogenin cleaves it into 3′and 5′halves.5′tiRNA halves were shown to repress protein translations.tRNA cleavage is thought of to be a cytoprotective mechanism by which cells evade apoptosis,however some data hints to the opposite;that tiRNA are cytotoxic or at least related to apoptosis initiation.tRNA cleavage also was shown to be affected by tRNA modifications via different enzymes in the cytosol and mitochondria.In this review,we will highlight the biology of tRNA cleavage,show the evidence of it being cytoprotective or a marker of cell death and shed a light on its role in disease models and human diseases as well as possible future directions in this field of RNA research.展开更多
The Polycomb group(PcG) proteins are a family of chromatin regulators and critical for the maintenance of cellular identity. The PcG machinery can be categorized into at least three multi-protein complexes, namely Pol...The Polycomb group(PcG) proteins are a family of chromatin regulators and critical for the maintenance of cellular identity. The PcG machinery can be categorized into at least three multi-protein complexes, namely Polycomb Repressive Complex 1(PRC1), PRC2, and Polycomb Repressive De UBiquitinase(PR-DUB).Their deregulation has been associated with human cancer initiation and progression. Here we review the updated understanding for Pc G proteins in transcription regulation and DNA damage repair and highlight increasing links to the hallmarks in cancer. Accordingly, we discuss some of the recent advances in drug development or strategies against cancers caused by the gain or loss of PcG functions.展开更多
It has been reported that one of the factors that promotes tumoral progression is the abnormal activation of the epithelial-mesenchymal transition program. This process is associated with tumoral cells acquiring invas...It has been reported that one of the factors that promotes tumoral progression is the abnormal activation of the epithelial-mesenchymal transition program. This process is associated with tumoral cells acquiring invasive and malignant properties and has the transcription factor zinc finger E-box-binding homeobox 1 （ZEB1） as one of its main activators. However, the role of ZEB1 in promoting malignancy in prostate cancer （PC, a） is still unclear. Here, we report that ZEB1 expression correlates with Gleason score in PCa samples and that expression of ZEB1 regulates epithelial-mesenchymal transition and malignant characteristics in PCa cell lines. The results showed that ZEB1 expression is higher in samples of higher malignancy and that overexpression of ZEB1 was able to induce epithelial-mesenchymal transition by upregulating the mesenchymal marker Vimentin and downregulating the epithelial marker E-Cadherin. On the contrary, ZEB 1 silencing repressed Vimentin expression and upregulated E-Cadherin. ZEB1 expression conferred enhanced motility and invasiveness and a higher colony formation capacity to 22Rvl cells whereas DU145 cells with ZEB1 silencing showed a decrease in those same properties. The results showed that ZEB1 could be a key promoter of tumoral progression toward advanced stages of PC, a.展开更多
LSD1 （KDM1 under the new nomenclature） was the first identified lysine-specific histone demethylase belonging to the flavin-dependent amine oxidase family. Here, we report that AOF1 （KDM1B under the new nomenclatur...LSD1 （KDM1 under the new nomenclature） was the first identified lysine-specific histone demethylase belonging to the flavin-dependent amine oxidase family. Here, we report that AOF1 （KDM1B under the new nomenclature）, a mammalian protein related to LSD1, also possesses histone demethylase activity with specificity for H3K4mel and H3K4me2. Like LSD1, the highly conserved SWIRM domain is required for its enzymatic activity. However, AOF1 differs from LSD1 in several aspects. First, AOF1 does not appear to form stable protein complexes containing histone deacetylases. Second, AOF1 is found to localize to chromosomes during the mitotic phase of the cell cycle, whereas LSD1 does not. Third, AOF1 represses transcription when tethered to DNA and this repression activity is independent of its demethylase activity. Structural and functional analyses identified its unique N-terminal Zf-CW domain as essential for the demethylase activity-independent repression function. Collectively, our study identifies AOF1 as the second histone demethylase in the family of flavin-dependent amine oxidases and reveals a demethylase-independent repression function of AOF1.展开更多
Interferon-gamma （IFN-γ） is a major proinflammatory effector and regulatory cytokine produced by activated T cells and NK cells. IFN-γ has been shown to play pivotal roles in fundamental immunological processes su...Interferon-gamma （IFN-γ） is a major proinflammatory effector and regulatory cytokine produced by activated T cells and NK cells. IFN-γ has been shown to play pivotal roles in fundamental immunological processes such as inflammatory reactions, cell-mediated immunity and autoimmunity. A variety of human disorders have now been linked to irregular IFN-γ expression. In order to achieve proper IFN-γ-mediated immunological effects, IFN-γ expression in T cells is subject to both positive and negative regulation. In this study, we report for the first time the negative regulation of IFN-γ expression by Prospero-related Homeobox （Proxl）. In Jurkat T cells and primary human CD4＋ T cells, Proxl expression decreases quickly upon T cell activation, concurrent with a dramatic increase in IFN-γ expression. Reporter analysis and chromatin immunoprecipitation （CHIP） revealed that Proxl associates with and inhibits the transcription activity of IFN-γ promoter in activated Jurkat T cells. Co-immunoprecipitation and GST pull-down assay demonstrated a direct binding between Proxl and the nuclear receptor peroxisome proliferator-activated receptor gamma （PPARγ）, which is also an IFN-γ repressor in T cells. By introducing deletions and mutations into Proxl, we show that the repression of IFN-γ promoter by Proxl is largely dependent upon the physical interaction between Proxl and PPARγ. Furthermore, PPARγ antagonist treatment removes Proxl from IFN-γ promoter and attenuates repression of IFN-γ expression by Proxl. These findings establish Proxl as a new negative regulator of IFN-γ expression in T cells and will aid in the understanding of IFN-γ transcription regulation mechanisms.展开更多
In this study,a modified continuous-flow nitrifying reactor was successfully operated for rapid cultivation of micro-granules and achieving robust nitritation.Results showed that sludge granulation with mean size of c...In this study,a modified continuous-flow nitrifying reactor was successfully operated for rapid cultivation of micro-granules and achieving robust nitritation.Results showed that sludge granulation with mean size of ca.100μm was achieved within three weeks by gradually increasing settling velocity-based selection pressure from 0.48 to 0.9 m/hr.Though Nitrospira like nitrite-oxidizing bacteria(NOB)were enriched in the micro-granules with a ratio between ammonia-oxidizing bacteria(AOB)and NOB of 5.7%/6.5% on day 21,fast nitritation was achieved within one-week by gradually increasing of influent ammonium concentration(from 50 to 200 mg/L).Maintaining ammonium in-excess was the key for repressing NOB in the micro-granules.Interestingly,when the influent ammonium concentration switched back to 50 mg/L still with the residual ammonium of 15–25 mg/L,the nitrite accumulation efficiency increased from 90%to 98%.Experimental results suggested that the NOB repression was intensified by both oxygen and nitrite unavailability in the inner layers of micro-granules.Unexpectedly,continuous operation with ammonium in excess resulted in overproduction of extracellular polysaccharides and overgrowth of some bacteria(e.g.,Nitrosomonas,Arenimonas,and Flavobacterium),which deteriorated the micro-granule stability and drove the micro-granules aggregation into larger ones with irregular morphology.However,efficient nitritation was stably maintained with extremely high ammonium oxidation potential(>50 mg/g VSS/hr)and nearly complete washout of NOB was obtained.This suggested that smooth and spherical granule was not a prerequisite for achieving NOB wash-out and maintaining effective nitritation in the granular reactor.Overall,the microgranules exhibited a great practical potential for high-rate nitritation.展开更多
In order to understand the behavior of ligninolytic enzyme production by white rot fungi Phanerochaete chrysosporium, study on time courses and a mathematical model for the production of lignin peroxidase (LiP) and ma...In order to understand the behavior of ligninolytic enzyme production by white rot fungi Phanerochaete chrysosporium, study on time courses and a mathematical model for the production of lignin peroxidase (LiP) and manganese peroxidase (MnP) of the fungi was undertaken. Based on the Monod-Jacob operon model, the ligninolytic enzyme would be synthesized in the absence of a related repressor. The repressor is assumed to be active in the presence of ammonia nitrogen, and as combined as co-repressor, it causes the inhibition of enzyme synthesis. The model can explain the mechanism of extracellular ligninolytic enzyme production by white rot fungi. The results,as predicted by the model, correspond closely to those observed in experimental studies. In addition, some light is also shed on unmeasured variables, such as the concentrations of repressor and mRNA that are related to the enzyme synthesis.展开更多
Rice grain size is an important trait that affects rice yield and quality, and thus the identification of genes related to grain size is of great significance for improving rice yield and quality. Many genes related t...Rice grain size is an important trait that affects rice yield and quality, and thus the identification of genes related to grain size is of great significance for improving rice yield and quality. Many genes related to grain size, such as DEP1(Huang et al., 2009),GW5(Liu et al., 2017).展开更多
文摘The influence of high temperature repressing treatment on the segregation of phosphorus in the 93W alloy was carefully investigated by means of Auger electron spectroscope,EPMA, TEM and SEM.The segregation of phosphorus has been observed at the tungsten-tungsten grain boundaries,particularly at the tungsten-matrix interphases when the specimens were kept at the temperature in the range of 1200—1500℃ ,followed by furnace cooling.However, no segregation of phosphorus was observed at the interfaces after the specimens were re- pressed at the range of temperature,followed by furnace cooling.After investigation,the dis- locations in the matrix phase of as-repressed specimens directly influenced the phosphorus segregation to the interfaces.After annealing,the mechanical properties were reduced because of the phosphorus segregation at the interface boundaries.
文摘Increasing density is one of the important factors for producing high quality powder metallurgy （PM） parts, which has beneficial effect on mechanical properties. One of the common techniques for achieving this goal is double compacting, which seems to be a potentially attractive method in PM route, also for Cr-Mo alloyed-steels. The objective of this research was to investigate the effect of first compacting pressure and intermediate annealing temperature on attaining higher densities and minimum interconnected porosity for Cr-Mo pre-alloyed steel. The effect of mentioned parameters was studied by measuring density, transverse rupture strength and macrohardness of repressed samples. The results show that for each first compacting pressure, the density range of repressed samples increases with the increasing annealing temperature up to a certain limit, due to C dissolution which causes free porosity and further densifieation. Annealing temperatures higher than optimum one should be avoided, since too much carbon dissolution results in harder and less deformable compacts. On the other hand, with regard to repressed density and other resulted properties, the amount of first compacting pressure offers considerable advantage in obtaining higher level of density and consequently improved mechanical properties.
文摘Aiming at the corrosion issue of oil extraction equipments caused by sulfate-reducing bacteria （SRB） reproducing in oil field affusion system, we studied the dominant strains in the SRB community and the impact of four ecological factors on the growth of the dominant strains：temperature, pH, mineralization degree and concentration of PAM （Polyacrylamine）. The feasibility of repressing the growth of SRB by changing ecological factors was also discussed. The results indicate that Desutfobacter （one genus of SRB） is the preponderant strains of the system, and the order of the effect of four ecological factors is pH 〉 temperature 〉 the concentrations of PAM 〉 mineralization degree. The optimal pH for the highest growth rate of SRB is 8.0. No growth of SRB was observed when pH 〈 4 or pH 〉 12. The optimal temperature for the growth of SRB is 40 ℃ and the ecological amplitude is 20 -50 ℃. The appropriate concentration values of PAM is 400 -800 mg/L, beyond of which the multiplication rate and growth quantity 6f cell decrease obviously. The effect of mineralization degree of SO4^2- , HCO^3- and Na^＋ on the growth of SRB has reached an extremely remarkable level, and the change of three ions＇ concentration in water obviously effects SRB： The optimum values on the main ions in the system are Cl- of 200mg/L, HCO^3- of 900 mg/L,SO4^2- of 400 mg/L, Mg^2＋ of 60 mg/L and Na^＋ of 900 mg/L. Our results indicate that it is possible to repress the growth of SRB by changing the ecological factors in nil field affusion system.
基金supported by the National Natural Science Foundation of China(32230043 and 32371092)the Ministry of Science and Technology of China(2019YFA0707103)+1 种基金Das Chinesisch-Deutsche Zentrum für Wissenschaftsförderung(M-0093)the High-performance Computing Platform of Peking University.
文摘Neural activities differentiating bodies versus non-body stimuli have been identified in the occipitotemporal cortex of both humans and nonhuman primates.However,the neural mechanisms of coding the similarity of different individuals’bodies of the same species to support their categorical representations remain unclear.Using electroencephalography(EEG)and magnetoencephalography(MEG),we investigated the temporal and spatial characteristics of neural processes shared by different individual body silhouettes of the same species by quantifying the repetition suppression of neural responses to human and animal(chimpanzee,dog,and bird)body silhouettes showing different postures.Our EEG results revealed significant repetition suppression of the amplitudes of early frontal/central activity at 180–220 ms(P2)and late occipitoparietal activity at 220–320 ms(P270)in response to animal(but not human)body silhouettes of the same species.Our MEG results further localized the repetition suppression effect related to animal body silhouettes in the left supramarginal gyrus and left frontal cortex at 200–440 ms after stimulus onset.Our findings suggest two neural processes that are involved in spontaneous categorical representations of animal body silhouettes as a cognitive basis of human-animal interactions.
基金Beijing High-Level Innovation and Entrepreneurship Talent Support Plan,Grant/Award Number:G04070024National Natural Science Foundation of China,Grant/Award Number:82073122。
文摘Background:Globally,breast cancer constitutes the predominant malignancy in women.Abnormal regulation of epigenetic factors plays a key role in the development of tumors.Anti-apoptosis is a characteristic of tumor cells.Therefore,exploring and identifying relevant epigenetic factors that regulate the apoptosis of tumor cells is the foundation for clarifying the pathogenesis of tumors and achieving precision antitumor therapy.Method:This study focused on exploring the epigenetic mechanism of FOXK1 in the development of estrogen receptor-positive(ER^(+))breast cancer.We used overexpressing FLAG-FOXK1 MCF-7 cells to perform silver staining mass spectrometry analysis and conducted Co-IP experiments to verify the interactions.ChIP-seq was conducted on MCF-7 cells to examine FOXK1's binding across the genome and its transcriptional target sites.To validate the ChIP-seq results,qChIP,western blotting,and quantitative polymerase chain reaction(qPCR)were performed.Through TUNEL assay,cell counting assay,colony formation assay,and the mouse xenograft models,the effect of FOXK1 on breast cancer progression was detected.Finally,by analyzing online databases,the correlation between FOXK1 and the survival of breast cancer patients was examined.Results:FOXK1 interacts with the REST/CoREST transcriptional corepression complex to transcriptionally inhibit target genes representing the apoptotic pathway.Abnormally high expression of FOXK1 prevents the apoptosis of ER+breast cancer cells in vitro and promotes ER+breast tumor progression in vivo.Furthermore,the expression of FOXK1 is negatively correlated with the survival of ER+breast cancer patients.Conclusion:FOXK1 promotes ER+breast carcinogenesis through anti-apoptosis and acts as a potential target for ER+breast cancer treatment.
基金We thank Prof.Chengjiang Gao and Prof.Wei Zhao for their critically reading of the paper.This work was supported by the National Natural Science Foundation of China(81571523 and 31872810)the Natural Science Foundation of Shandong Province(ZR2016HZ01)the Key Research and Development Program of Shandong Province(2016ZDJS07A08 and 2017GSF218027).
文摘Toll-like receptors (TLRs) play critical roles in innate immunity and inflammation. The molecular mechanisms by which TLR signaling is fine-tuned remain to be completely elucidated. Cullin 4B (CUL4B), which assembles the CUL4B-RING E3 ligase complex (CRL4B), has been shown to regulate diverse developmental and physiological processes by catalyzing monoubiquitination for histone modification or polyubiquitination for proteasomal degradation. Here, we identified the role of CUL4B as an intrinsic negative regulator of the TLR-triggered inflammatory response. Deletion of CUL4B in macrophages increased the production of proinflammatory cytokines and decreased anti-inflammatory cytokine IL-10 production in response to pathogens that activate TLR3, TLR4, or TLR2. Myeloid cell-specific Cul4b knockout mice were more susceptible to septic shock when challenged with lipopolysaccharide, polyinosinic-polycytidylic acid or Salmonella typhimurium infection. We further demonstrated that enhanced TLR-induced inflammatory responses in the absence of CUL4B were mediated by increased GSK3β activity. Suppression of GSK3β activity efficiently blocked the TLR-triggered increase in proinflammatory cytokine production and attenuated TLR-triggered death in Cul4b mutant mice. Mechanistically, CUL4B was found to negatively regulate TLR-triggered signaling by epigenetically repressing the transcription of Pten, thus maintaining the anti-inflammatory PI3K-AKT-GSK3β pathway. The upregulation of PTEN caused by CUL4B deletion led to uncontrolled GSK3β activity and excessive inflammatory immune responses. Thus, our findings indicate that CUL4B functions to restrict TLR-triggered inflammatory responses through regulating the AKT-GSK3β pathway.
基金the Key Projects of Zhejiang Provincial Natural Science Foundation,China(Grant No.LZ23C130002)the National Natural Science Foundation of China(Grant No.32100161)+3 种基金the Zhejiang Science and Technology Major Program on Rice New Variety Breeding,China(Grant No.2021C02063)the Key R&D Project of China National Rice Research Institute(Grant No.CNRRI-2020-04)the Chinese Academy of Agricultural Sciences under the Agricultural Sciences and Technologies Innovation Program,the Youth innovation Program of Chinese Academy of Agricultural Sciences(Grant No.Y2023QC22)the Joint Open Competitive Project of the Yazhou Bay Seed Laboratory and China National Seed Company Limited(Grant Nos.B23YQ1514 and B23CQ15EP).
文摘The rice false smut disease, caused by Ustilaginoidea virens, has emerged as a significantglobal threat to rice production. The mechanism of carbon catabolite repression plays a crucial role in theefficient utilization of carbon nutrients and enzyme regulation in the presence of complex nutritionalconditions. Although significant progress has been made in understanding carbon catabolite repression infungi such as Aspergillus nidulans and Magnaporthe oryzae, its role in U. virens remains unclear. Toaddress this knowledge gap, we identified UvCreA, a pivotal component of carbon catabolite repression,in U. virens. Our investigation revealed that UvCreA localized to the nucleus. Deletion of UvCreA resultedin decreased growth and pathogenicity in U. virens. Through RNA-seq analysis, it was found that theknockout of UvCreA led to the up-regulation of 514 genes and down-regulation of 640 genes. Moreover,UvCreA was found to be involved in the transcriptional regulation of pathogenic genes and genesassociated with carbon metabolism in U. virens. In summary, our findings indicated that UvCreA isimportant in fungal development, virulence, and the utilization of carbon sources through transcriptionalregulation, thus making it a critical element of carbon catabolite repression.
文摘The specification of germ cells in zebrafish mostly relies on an inherited mechanism by which localized maternal determinants,called germ plasm,confer germline fate in the early embryo.Extensive studies have partially allowed the identification of key regulators governing germ plasm formation and subsequent germ cell development.RNA-binding proteins,acting in concert with other germ plasm components,play essential roles in the organization of the germ plasm and the specification,migration,maintenance,and differentiation of primordial germ cells.The loss of their functions impairs germ cell formation and causes sterility or sexual conversion.Evidence is emerging that they instruct germline development through differential regulation of mRNA fates in somatic and germ cells.However,the challenge remains to decipher the complex interplay of maternal germ plasm components in germ plasm compartmentalization and germ cell specification.Because failure to control the developmental outcome of germ cells disrupts the formation of gametes,it is important to gain a complete picture of regulatory mechanisms operating in the germ cell lineage.This review sheds light on the contributions of RNA-binding proteins to germ cell development in zebrafish and highlights intriguing questions that remain open for future investigation.
文摘Long non-coding RNA (lncRNA) refers to an over 200 nt functional RNA molecule that will not be translated into protein. Previously thought to be dark matters of the genome, lncRNAs have been gradually recognized as crucial gene regulators. Although tremendous progress has been made in animals and human, the study of lncRNAs in plant is still in its infancy. Here, we reviewed the biogenesis and regulation mechanisms of lncRNAs and summarized the achievements that have been made in plant lncRNA identification and functional characterization. Genome-wide identification has uncovered large amount of lncRNAs in Arabidopsis, Rice, Maize and Wheat, and more information from other plant species will be expected with the aid of deep sequencing technologies. Similar to other species, LncRNA-mediated gene regulation also widely exists in plants, even though only a few functionally characterized examples are available. Up to now, at least four divergent lncRNA-mediated regulation mechanisms have been unraveled, including target mimicry, transcription interference, PRC2 associated histone methylation and DNA methylation. lncRNAs may be involved in the regulation of flowering, male sterility, nutrition metabolism, biotic and abiotic stress response in plants.
文摘Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcription may be regulated epigenetically. Using a custom-designed microarray, here we examine the expression profile of IncRNAs in embryonic stem （ES） cells, lineage-restricted neuronal progenitor cells, and terminally differentiated fibroblasts. In addition, we also analyze the relationship between their expression and their promoter H3K4 and H3K27 methyla- tion patterns. We find that numerous lncRNAs in these cell types undergo changes in the levels of expression and promoter H3K4me3 and H3K27me3. Interestingly, lncRNAs that are expressed at lower levels in ES cells exhibit higher levels of H3K27me3 at their promoters. Consistent with this result, knockdown of the H3K27me3 methyltransferase Ezh2 results in derepression of these IncRNAs in ES cells. Thus, our results establish a role for Ezh2-mediated H3K27 methylation in lncRNA silencing in ES cells and reveal that lncRNAs are subject to epigenetic regulation in a similar manner to that of the protein-coding genes.
基金Project supported by the Fundamental Research Funds for the Central Universities from Lanzhou University (No.lzujbky-2014-87),China
文摘Polycomb group （PCG） complexes are epigenetic regulatory complexes that conduct transcriptional repression of target genes via modifying the chromatin. The two best characterized forms of PCG complexes, polycomb repressive complexes 1 and 2 （PRC1 and PRC2）, are required for maintaining the sternness of embryonic stem cells and many types of adult stem cells. The spectra of target genes for PRCs are dynamically changing with cell differentiation, which is essential for proper decisions on cell fate during developmental processes, Chromobox （CBX） family proteins are canonical components in PRC1, responsible for targeting PRC1 to the chromatin. Recent studies highlight the function specifications among CBX family members in undifferentiated and differentiated stem cells, which reveal the interplay between compositional diversity and functional specificity of PRCI. In this review, we summarize the current knowledge about targeting and functional mechanisms of PRCs, emphasizing the recent breakthroughs related to CBX proteins under a number of physiological and pathological conditions.
文摘Over the past decades,tRNA was found to be a rich hub of RNA modifications such as 1-methyladenosine and 5-methycytosine modifications and others,holding more than half of all modifications occurring in RNA molecules.Moreover,tRNA was discovered to be a source of various small noncoding RNA species,such as the stress induced angiogenin cleaved tRNA halves(tiRNA)or the miRNA like tRNA derived fragments.tRNA cleavage under stress was fist discovered in bacteria and later was found to be conserved across different species,including mammals.Under cellular stress conditions,tRNA undergoes conformational changes and angiogenin cleaves it into 3′and 5′halves.5′tiRNA halves were shown to repress protein translations.tRNA cleavage is thought of to be a cytoprotective mechanism by which cells evade apoptosis,however some data hints to the opposite;that tiRNA are cytotoxic or at least related to apoptosis initiation.tRNA cleavage also was shown to be affected by tRNA modifications via different enzymes in the cytosol and mitochondria.In this review,we will highlight the biology of tRNA cleavage,show the evidence of it being cytoprotective or a marker of cell death and shed a light on its role in disease models and human diseases as well as possible future directions in this field of RNA research.
基金supported by the National Key Research and Development Program (2017YFA0504102)the National Natural Science Foundation of China (81772676, 31970579)+3 种基金the Natural Science Foundation of Tianjin Municipal Science and Technology Commission (18JCJQJC48200)Key Research Project of Tianjin Education Commission (2020ZD13)Open grant from the Chinese Academy of Medical Sciences (157-Zk19-02 and Z20-04)the Talent Excellence Program from Tianjin Medical University and Research Project of Tianjin Education Commission。
文摘The Polycomb group(PcG) proteins are a family of chromatin regulators and critical for the maintenance of cellular identity. The PcG machinery can be categorized into at least three multi-protein complexes, namely Polycomb Repressive Complex 1(PRC1), PRC2, and Polycomb Repressive De UBiquitinase(PR-DUB).Their deregulation has been associated with human cancer initiation and progression. Here we review the updated understanding for Pc G proteins in transcription regulation and DNA damage repair and highlight increasing links to the hallmarks in cancer. Accordingly, we discuss some of the recent advances in drug development or strategies against cancers caused by the gain or loss of PcG functions.
文摘It has been reported that one of the factors that promotes tumoral progression is the abnormal activation of the epithelial-mesenchymal transition program. This process is associated with tumoral cells acquiring invasive and malignant properties and has the transcription factor zinc finger E-box-binding homeobox 1 （ZEB1） as one of its main activators. However, the role of ZEB1 in promoting malignancy in prostate cancer （PC, a） is still unclear. Here, we report that ZEB1 expression correlates with Gleason score in PCa samples and that expression of ZEB1 regulates epithelial-mesenchymal transition and malignant characteristics in PCa cell lines. The results showed that ZEB1 expression is higher in samples of higher malignancy and that overexpression of ZEB1 was able to induce epithelial-mesenchymal transition by upregulating the mesenchymal marker Vimentin and downregulating the epithelial marker E-Cadherin. On the contrary, ZEB 1 silencing repressed Vimentin expression and upregulated E-Cadherin. ZEB1 expression conferred enhanced motility and invasiveness and a higher colony formation capacity to 22Rvl cells whereas DU145 cells with ZEB1 silencing showed a decrease in those same properties. The results showed that ZEB1 could be a key promoter of tumoral progression toward advanced stages of PC, a.
基金We thank Dr Ramin Shiekhattar （Wistar Institute, USA） for the baculoviruses expressing Flag-LSD1 and Drs Jianguo Song and Degui Chen （Shanghai Institute of Biochemistry and Cell Biol- ogy, China） for anti-HDAC1 antibody and H3K36me2 antibody, respectively. This study was partially supported by grants from the National Natural Science Foundation of China （90919025, 30871381）, the Ministry of Science and Technology of China （2009CB918402, 2009CB825601） and the Research Platform for Cell Signaling Networks from the Science and Technology Com- mission of Shanghai Municipality （06DZ22923）.
文摘LSD1 （KDM1 under the new nomenclature） was the first identified lysine-specific histone demethylase belonging to the flavin-dependent amine oxidase family. Here, we report that AOF1 （KDM1B under the new nomenclature）, a mammalian protein related to LSD1, also possesses histone demethylase activity with specificity for H3K4mel and H3K4me2. Like LSD1, the highly conserved SWIRM domain is required for its enzymatic activity. However, AOF1 differs from LSD1 in several aspects. First, AOF1 does not appear to form stable protein complexes containing histone deacetylases. Second, AOF1 is found to localize to chromosomes during the mitotic phase of the cell cycle, whereas LSD1 does not. Third, AOF1 represses transcription when tethered to DNA and this repression activity is independent of its demethylase activity. Structural and functional analyses identified its unique N-terminal Zf-CW domain as essential for the demethylase activity-independent repression function. Collectively, our study identifies AOF1 as the second histone demethylase in the family of flavin-dependent amine oxidases and reveals a demethylase-independent repression function of AOF1.
文摘Interferon-gamma （IFN-γ） is a major proinflammatory effector and regulatory cytokine produced by activated T cells and NK cells. IFN-γ has been shown to play pivotal roles in fundamental immunological processes such as inflammatory reactions, cell-mediated immunity and autoimmunity. A variety of human disorders have now been linked to irregular IFN-γ expression. In order to achieve proper IFN-γ-mediated immunological effects, IFN-γ expression in T cells is subject to both positive and negative regulation. In this study, we report for the first time the negative regulation of IFN-γ expression by Prospero-related Homeobox （Proxl）. In Jurkat T cells and primary human CD4＋ T cells, Proxl expression decreases quickly upon T cell activation, concurrent with a dramatic increase in IFN-γ expression. Reporter analysis and chromatin immunoprecipitation （CHIP） revealed that Proxl associates with and inhibits the transcription activity of IFN-γ promoter in activated Jurkat T cells. Co-immunoprecipitation and GST pull-down assay demonstrated a direct binding between Proxl and the nuclear receptor peroxisome proliferator-activated receptor gamma （PPARγ）, which is also an IFN-γ repressor in T cells. By introducing deletions and mutations into Proxl, we show that the repression of IFN-γ promoter by Proxl is largely dependent upon the physical interaction between Proxl and PPARγ. Furthermore, PPARγ antagonist treatment removes Proxl from IFN-γ promoter and attenuates repression of IFN-γ expression by Proxl. These findings establish Proxl as a new negative regulator of IFN-γ expression in T cells and will aid in the understanding of IFN-γ transcription regulation mechanisms.
基金supported by the National Natural Science Foundation of China (Nos. 51808367 and 51878430)
文摘In this study,a modified continuous-flow nitrifying reactor was successfully operated for rapid cultivation of micro-granules and achieving robust nitritation.Results showed that sludge granulation with mean size of ca.100μm was achieved within three weeks by gradually increasing settling velocity-based selection pressure from 0.48 to 0.9 m/hr.Though Nitrospira like nitrite-oxidizing bacteria(NOB)were enriched in the micro-granules with a ratio between ammonia-oxidizing bacteria(AOB)and NOB of 5.7%/6.5% on day 21,fast nitritation was achieved within one-week by gradually increasing of influent ammonium concentration(from 50 to 200 mg/L).Maintaining ammonium in-excess was the key for repressing NOB in the micro-granules.Interestingly,when the influent ammonium concentration switched back to 50 mg/L still with the residual ammonium of 15–25 mg/L,the nitrite accumulation efficiency increased from 90%to 98%.Experimental results suggested that the NOB repression was intensified by both oxygen and nitrite unavailability in the inner layers of micro-granules.Unexpectedly,continuous operation with ammonium in excess resulted in overproduction of extracellular polysaccharides and overgrowth of some bacteria(e.g.,Nitrosomonas,Arenimonas,and Flavobacterium),which deteriorated the micro-granule stability and drove the micro-granules aggregation into larger ones with irregular morphology.However,efficient nitritation was stably maintained with extremely high ammonium oxidation potential(>50 mg/g VSS/hr)and nearly complete washout of NOB was obtained.This suggested that smooth and spherical granule was not a prerequisite for achieving NOB wash-out and maintaining effective nitritation in the granular reactor.Overall,the microgranules exhibited a great practical potential for high-rate nitritation.
基金Supported by the National Natural Science Foundation of China (No. 29976038).
文摘In order to understand the behavior of ligninolytic enzyme production by white rot fungi Phanerochaete chrysosporium, study on time courses and a mathematical model for the production of lignin peroxidase (LiP) and manganese peroxidase (MnP) of the fungi was undertaken. Based on the Monod-Jacob operon model, the ligninolytic enzyme would be synthesized in the absence of a related repressor. The repressor is assumed to be active in the presence of ammonia nitrogen, and as combined as co-repressor, it causes the inhibition of enzyme synthesis. The model can explain the mechanism of extracellular ligninolytic enzyme production by white rot fungi. The results,as predicted by the model, correspond closely to those observed in experimental studies. In addition, some light is also shed on unmeasured variables, such as the concentrations of repressor and mRNA that are related to the enzyme synthesis.
基金supported by the grants from the National Key Research and Development Program of China (2016YFD0100406)the Rice Molecular Design Breeding (2016YFD0101801)+1 种基金the National Natural Science Foundation of China (91535102 and 31771760)the Open Research Fund of State Key Laboratory of Hybrid Rice (Hunan Hybrid Rice Research Center) (2016KF09)
文摘Rice grain size is an important trait that affects rice yield and quality, and thus the identification of genes related to grain size is of great significance for improving rice yield and quality. Many genes related to grain size, such as DEP1(Huang et al., 2009),GW5(Liu et al., 2017).
