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With the clarification of the CO2 abatement targets and pathways, the management and control of non-CO2 greenhouse gases (GHGs) have been widely emphasized. As the potent GHGs restricted by the Kyoto Protocol, methane (CH4) and sulfur hexafluoride (SF6) emissions contribute to a significant and increasing share of the total global GHG emissions, resulting in a continuous impact on the environment. Hence, the abatement of CH4 and SF6, the potent GHGs, is a matter of urgency. This paper focuses on recent advances in abatement of lean CH4 and SF6 waste gas. Firstly, a systematic review of abatement technologies for lean CH4 is presented, and two methods, namely, pressure swing adsorption and catalytic combustion, are emphasized. Additionally, the current status of four mainstream methods such as adsorption separation, thermal (catalytic) degradation, photocatalytic degradation, and non-thermal plasma degradation, as well as emerging technologies for SF6 abatement are summarized, and the inherent shortcomings and industrialization potentials of each technology are analyzed from multiple perspectives. This review demonstrates that, under dual-carbon target, existing abatement technologies are inadequate to meet the complex and diverse demands of the power and coal industries. There are many drawbacks for lean CH4 abatement technologies such as high investment in utilization devices, low processing capacity, high operating cost and requirement of high CH4 concentration. Degradation technologies for SF6 waste gas also suffer from low energy efficiency, high investment in catalytic degradation devices, and secondary pollution of degradation products. Based on this, two large-scale processing schemes with high feasibility are proposed. Finally, the current research hotspots, challenges, and future directions are put forward. This review aims to contribute some new perspectives to the abatement efforts of non-CO2 GHGs, so that the dual-carbon target can be realized as soon as possible.

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Heavy metal pollutants such as Hg, As, Pb, Cr, and Cd emitted from coal and waste combustion have received widespread attention. In this study, we systematically investigated the emission characteristics of heavy metals in waste incineration and coal-fired flue gases, focused on testing the removal effect of self-made cold electrode electrostatic precipitator (CE-ESP) on heavy metals in flue gas, and made a comparative analysis with the existing air pollution control devices (APCDs). Test results from waste incineration power plant showed that each APCD showed a certain effect on the removal of heavy metals in condensable particulate matter (CPM), with an average removal efficiency of bag filter was 86%, but its effect on Hg removal was slightly worse. Under the coupled field with electrified cold electrode plate operation mode, the average removal efficiency of CE-ESP on heavy metals in CPM was as high as 93%, including 76% for Hg. The removal efficiency of heavy metals (especially Hg) in CPM increased with the increase of flue gas temperature difference between inlet and outlet of CE-ESP. Test results from this coal-fired power plant showed that heavy metals were enriched in fly ash to a higher degree than in slag, the synergistic control of heavy metals in submicron particulate matter by the dust remover was not obvious, and there was a significant correlation between each heavy metal emission factor and its content in coal. Under the temperature field with non-electric cold electrode plate operation mode, the overall effect of CE-ESP on the removal of gaseous heavy metals was better than that of particulate heavy metals. Under the conventional electric field operation mode, CE-ESP was less effective in removing particulate Cr and gaseous Hg0. Under the coupled field with electrified cold electrode plate operation mode, the average removal efficiencies of CE-ESP for particulate and gaseous heavy metals were 82.37% and 76.16%, respectively.

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Carbon emission (CE) has led to increasingly severe climate problems. The key to reducing CE is to identify the dominant influencing factors and explore their influence degree. The CE data of 30 provinces from 1997 to 2020 in China were calculated by IPCC method. Based on this, the importance order of six factors included GDP, Industrial Structure (IS), Total Population (TP), Population Structure (PS), Energy Intensity (EI) and Energy Structure (ES) affecting the CE of China's provinces were obtained by using symbolic regression, then the LMDI and the Tapio models were established to deeply explore the influence degree of different factors on CE. The results showed that the 30 provinces were divided into five categories according to the primary factor, GDP was the most important factor, followed by ES and EI, then IS, and the least TP and PS. The growth of per capita GDP promoted the increase of CE, while reduced EI inhibited the increase of CE. The increase of ES promoted CE in some provinces but inhibited in others. The increase of TP weakly promoted the increase of CE. These results can provide some references for governments to formulate relevant CE reduction policies under dual carbon goal.

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The exploration of cost-effective and sustainable biomass-derived carbon materials as electrodes for energy conversion and storage has gained extensive attention in recent research studies. However, the selection of the biomass and the electrochemical performance regulation of the derived biochar, as well as their interrelationship still remain challenging for practical application. Herein, corn wastes with high carbon content (>40%), corn cob and corn silk, were selected as precursors for the preparation of high value-added and high yield carbon materials via a modified synthetic process. Uniquely, this work put emphasis on the theoretical and experimental investigations of how the biomass properties influence the composition and nanostructure regulation, the electrolyte ion adsorption free energy, and the electrical conductivity of the derived carbon materials as well as their electrochemical performance optimization. Owing to the favorable specific surface area, the hierarchical porous structure, and the diverse elemental distribution, corn cob and corn silk derived carbon materials (CBC and SBC) present great potential as promising electrodes for alkaline aqueous zinc batteries and supercapacitors. The assembled CBC//Zn and SBC//Zn zinc batteries deliver high energy densities of 63.0 Wh kg-1 and 39.1 Wh kg-1 at a power density of 575 W kg-1, with excellent cycling performance of 91.1% and 84.3% capacitance retention after 10,000 cycles. As for the assembled symmetric supercapacitors, high energy densities of 14.9 Wh kg-1 and 13.6 Wh kg-1, and superior long-term cycling stability of 99.3% and 96.6% capacitance retention after 20,000 cycles could be achieved. This study highlights the advantages of utilizing corn cob and corn silk as carbon sources on the designed synthesis of carbon electrodes, and presents a meaningful perspective in the investigation of biomass-derived carbon materials and their potential applications in rechargeable devices.

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ZnS@In2S3 core-shell structures with high photocatalytic activity have been delicately designed and synthesized. The unique structure and synergistic effects of the composites have an important influence on the improvement of photocatalytic activity. The photocatalytic activity has been studied by photodegrading individual eosin B (EB) and the mixture solution consisting of eosin B and rhodamine B (EB-RhB) in the presence of hydrogen peroxide (H2O2) under simulated sunlight irradiation. The results show that all of the photocatalysts with different contents of In2S3 exhibit enhanced catalytic activity compared to pure ZnS for the degradation of EB and EB-RhB solution. When the theoretical molar ratio of ZnS to In2S3 was 1:0.5, the composite presents the highest photocatalytic efficiency, which could eliminate more than 98% of EB and 94% of EB-RhB. At the same time, after five cycles of photocatalytic tests, the photocatalytic efficiency could be about 96% for the degradation of the EB solution, and relatively high photocatalytic activity could also be obtained for the degradation of the EB-RhB mixed solution. This work has proposed a facile synthetic process to realize the controlled preparation of core-shell ZnS@In2S3 composites with effectively modulated structures and compositions, and the composites have also proved to be high-efficiency photocatalysts for the disposal of complicated pollutants.

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The amount of China's sulfur dioxide emission remains significantly large in recent years. To further reduce sulfur dioxide emission, the key is to find out the leading factors affecting sulfur dioxide emission and then take measures to control it accordingly. In order to investigate the influential factors of sulfur dioxide emission of various provinces, the data of sulfur dioxide emission of 30 provinces in China from 2001 to 2020 were collected. We established the symbolic regression model to explore the relationship between the GDP (x1), total population (x2), total energy consumption (x3), thermal power installed capacity (x4), and sulfur dioxide emission (dependent variable) for each province. The results show that the amount of China's total sulfur dioxide emission and sulfur dioxide emission in most provinces meet the environmental Kuznets curve (EKC). The influential degree of the factors affecting China's sulfur dioxide emission are GDP, total energy consumption, thermal power installed capacity, and total population. The provinces with the primary factor of GDP have the lowest average total energy consumption and average thermal power installed capacity, and their average sulfur dioxide emissions are also relatively low. The provinces with the primary factor of GDP do not show obvious geographical characteristics, but the provinces with the primary factor of total energy consumption are all distributed in southern China. Based on the research results, some control measures are also put forward.

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In order to study the impact of the "carbon peak and neutrality" mode on future power generation and the environment in China, a Verhulst gray model was established to predict the development of the power generation industry from 2021 to 2060 under the non-"carbon peak and neutrality" mode. In addition, based on the "China 2030 Energy and Power Development Planning Research and 2060 Outlook Report," the development of the power generation industry from 2021 to 2060 under the "carbon peak and neutrality" mode was obtained, and the development scenarios of the future power generation industry in China under two models were compared and studied. The emission factors and emission reduction factors of CO2, SO2, NOx, PM, PM10, and PM2.5 were constructed through the conservation of elements and the generating performance standard, and then four environmental benefits A1-A4 were defined. The results showed that the installed capacity of thermal power will reach the carbon peak in 2026 under the "carbon peak and neutrality" mode. To achieve the carbon neutralization, the installed capacity of thermal power will be reduced by an average of 28 million kilowatts per year after 2026, and the installed capacity of renewable energy generated is required to increase by 154 million kilowatts per year after 2020. Compared with that in the non-"carbon peak and neutrality" mode, the installed capacity of thermal power generation will be greatly reduced, and the installed capacity of renewable energy power generation will be greatly increased under the "carbon peak and neutrality" mode, resulting in huge A1 and A2 environmental benefits. In the next four decades, the cumulative emission reductions in CO2, SO2, NOx, PM, PM10, and PM2.5 thermal power generation A1 are predicted to be 6.64×1010 tons, 1.54×107 tons, 1.55×107 tons, 3.18×106 tons, 1.71×106tons, and 2.23×105 tons, respectively. The cumulative emission reductions of renewable energy power generation A2 will be 5.77×1010 tons, 1.64×107 tons, 1.42×107 tons, 2.86×106 tons, 1.54×106 tons, and 2×105 t tons, respectively. Under the "carbon peak and neutrality" mode, compared with those from coal-fired power generation, the environmental benefits A3 and A4 produced by the relative cleanliness of renewable energy and nuclear power indicated that the cumulative emission reductions (A3+A4) in clean energy power generation of CO2, SO2, NOx, PM, PM10, and PM2.5 in the next four decades will be 3.014×1011 tons, 7.292×107 tons, 7.119×107 tons, 1.454×107 tons, 7.827×106tons, and 1.018×106 tons, respectively.

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Dioxins are a kind of persistent organic pollutants (POPs) with extremely toxic. Municipal solid waste incineration (MSWI) process has become one of the most dominant discharge sources of dioxins. A comprehensive discussion about dioxin formation mechanisms was reviewed in this paper, and the mechanisms of high-temperature gas-phase reaction and "de novo" synthesis were systematically illustrated in the form of diagrams. What's more, the effects of various influencing factors on the formation of PCDD/Fs were briefly analyzed in the form of a table. We believed that temperature, catalyst, chlorine source, carbon source, oxygen concentration and moisture were necessary factors for PCDD/Fs formation. Control technologies of dioxins in MSWI process were summarized subsequently from three stages: pre-combustion, in-combustion and post-combustion, and a device for synergistic removal of dioxins based on multi-field force coupling and technical routes for controlling dioxin emissions were proposed, so as to provide mechanisms and methods for effectively reducing the emission concentration of dioxins. An introduction was also conducted of dioxin control technologies in municipal solid waste incineration fly ash (MSWI-FA) in this paper, and their mechanisms, advantages, disadvantages and technical maturity were illustrated in the form of diagrams, which can provide theory and reference for in-depth research of follow-up scholars and industrial application of dioxin control technologies. Finally, current research hotspots, challenges and future research directions were proposed.Implications: In this paper, the main research contents and achievements are as follows: With the emphasis placed on the formation mechanism of dioxins and effects of various influencing factors on the formation of PCDD/Fs. The control technology of dioxins in MSWI process is summarized subsequently from three stages: pre-combustion, in-combustion and post-combustion.A device for synergistic removal of dioxins based on multi-field force coupling and technical routes for controlling dioxin emissions are proposed.A systematic review is conducted of the research progress on control technologies of dioxins in MSWI fly ash in the most recent years.The mechanisms, advantages, disadvantages and technical maturity of PCDD/Fs degradation technologies in MSWI fly ash are illustrated in the form of diagrams.Current research hotspots, challenges and future research directions are proposed.

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METHODS: Two datasets were used as training and validation cohorts to establish the predictive model. We used three types of screening criteria: background analysis, pathway analysis, and functional analysis provided by the cBioportal website. Fisher's exact test and multivariable logistic regression were performed to screen out related genes. Furthermore, we performed receiver operating characteristic (ROC) and Kaplan-Meier curve analyses to evaluate the correlation between the selected genes and overall survival. RESULT: We screened five genes (KNL1, NRXN1, C6, CCDC169-SOHLH2, and TTN) that were highly related to recurrence of GC. The area under the receiver operating characteristic (ROC) curve was 0.813, which was much higher than that of the baseline model (AUC = 0.699). This result suggested that the mutation of five selected genes had a significant effect on the prediction of recurrence compared with other factors (age, stages, history, etc.). Furthermore, the Kaplan-Meier estimator also revealed that the mutation of five genes positively correlated with patient survival. CONCLUSIONS: The patients who have mutations in these five genes may experience longer survival than those who do not have mutations. This five-gene panel will likely be a practical tool for prognostic evaluation and will provide another possible way for clinicians to determine therapy.

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Growth of the cholera bacterium Vibrio cholerae in a biofilm community contributes to both its pathogenicity and survival in aquatic environmental niches. The major components of V. cholerae biofilms include Vibriopolysaccharide (VPS) and the extracellular matrix proteins RbmA, RbmC, and Bap1. To further elucidate the previously observed overlapping roles of Bap1 and RbmC in biofilm architecture and surface attachment, here we investigated the structural and functional properties of Bap1. Soluble expression of Bap1 was possible only after the removal of an internal 57-amino-acid-long hydrophobic insertion sequence. The crystal structure of Bap1 at 1.9 Å resolution revealed a two-domain assembly made up of an eight-bladed ß-propeller interrupted by a ß-prism domain. The structure also revealed metal-binding sites within canonical calcium blade motifs, which appear to have structural rather than functional roles. Contrary to results previously observed with RbmC, the Bap1 ß-prism domain did not exhibit affinity for complex N-glycans, suggesting an altered role of this domain in biofilm-surface adhesion. Native polyacrylamide gel shift analysis did suggest that Bap1 exhibits lectin activity with a preference for anionic or linear polysaccharides. Our results suggest a model for V. cholerae biofilms in which Bap1 and RbmC play dominant but differing adhesive roles in biofilms, allowing bacterial attachment to diverse environmental or host surfaces.

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An ethylene/air inverse diffusion flame (IDF) burner was employed to generate a stable flame, and selenium was introduced into the combustion flame in vapor phase under different air-fuel ratio (A/F) with SO2 additive. At different height above burner (HAB) along the flame edge, selenium of different speciation (gaseous selenium and particulate selenium) was sampled via the U.S. EPA method 29, and the samples were determined by hydride generation atomic fluorescence spectrometry (HG-AFS), in order to study the mechanism of transformation and enrichment behavior of selenium during the combustion process. The results showed that selenium presented in vapor phase, crossing the flame into air, which means gaseous phase is the main form of selenium during combustion process. Both gaseous selenium and particulate selenium increased with elevated temperature from 820K to 1650K, suggesting that higher temperature is beneficial to the release of selenium. Low concentration of sulfur dioxide would increase the concentration of particulate selenium and gaseous selenium, and accelerate the release of selenium. Implications: The enrichment behavior of selenium and its transformation in combustion flame were studied. The results showed that gaseous selenium is found in higher quantity in compared to particulate selenium during combustion. Higher temperature and air-fuel ratio will cause an increase in the formation of selenium. While the presence of sulfur dioxide in a range of 0-200 ppm will promote the release of selenium, higher sulfur dioxide level in a range of 200-350 ppm will have a reverse effect.

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BACKGROUND/AIM: The ELAVL4 (HuD) is a neuron-specific RNA-binding protein expressed in 100% of small cell lung cancer (SCLC) cells and over 50% of neuroblastoma cells. The aim of this study was to investigate the serum HuD concentration in SCLC patients and the possibility of its utilization as a biomarker of small cell lung cancer. MATERIALS AND METHODS: Our study included 47 SCLC cases and 29 normal controls. Indirect competitive inhibition ELISA method was established to detect HuD antigen of serum samples. To design the ELISA system, purified antigen and real positive and negative serum samples were used, and checkerboard titration was performed. The value of current serum biomarkers (Pro-GRP, NSE, CYFRA21-1 and CEA) was obtained from a clinical laboratory. RESULTS: The HuD antigen concentration in the SCLCgroup was significantly higher than that in the normal group (p<0.01). The cut-off value, specificity and sensitivity were 60 ng/ml, 89.7% and 74.5%, respectively. The best linear range was 9.75~600 ng/ml. The sensitivity of the HuD-ELISA assay was much better than the current biomarkers-CEA, NSE and pro-GRP. Also,it was equal to or better than the combined use of two or three indicators. CONCLUSION: The high titres of HuD in SCLC patients and preferable consistency suggested that HuD may serve as a potential diagnostic criterium for SCLC and may serve as a marker of disease progression.

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MicroRNAs (miRNAs/miRs) are short non-coding RNAs (between 20 and 22 nucleotides) that regulate gene expression by binding to the 3'-untranslated region of target mRNA, and preventing protein translation or inducing mRNA destabilization. miRNAs are predicted to target ~60% of all mRNAs, therefore providing a marked degree of regulation of a number of cellular processes. In the present study, the expression of miR-548c-3p was determined by reverse transcription-quantitative polymerase chain reaction analysis and demonstrated to be markedly downregulated in clinical malignant glioma tissues and the glioma T98G cell line compared with normal human brain tissue. Transfection of miR-548c-3p inhibited cell proliferation by inducing G1 cell cycle arrest and also inhibited the migration of the T98G cells in vitro. Furthermore, a bioinformatic algorithm and a luciferase reporter assay identified proto-oncogene c-Myb (c-Myb) as a potential direct target of miR-548c-3p. Further experiments demonstrated that the inhibition of c-Myb by miR-548c-3p partially mediated the antitumor effect of miR-548c-3p. The results of the present study provide the novel insight that miR-548c-3p inhibits glioma tumorigenesis by targeting c-Myb. Therefore, miR-548c-3p may contribute to the development of improved glioma treatment.

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Mammalian Sirtuin proteins (SIRTs) are homologs of yeast Sir2, and characterized as class III histone deacetylases of NAD(+) dependence. Unlike their lower counterparts that are directly involved in the extending of lifespan, mammalian SIRTs mainly function in metabolism and cellular homeostasis, among them, SIRT7 is the least understood. SIRT7 is localized in the nucleus and rich in nucleoli associated with RNA polymerase I, and correlated with cell proliferation. In contrast, SIRT7 has recently been demonstrated to specifically deacetylate H3K18ac in the chromatin, and in most cases represses proliferation. Although MicroRNA as miR-125b has been reported to down-regulate SIRT7 by binding to its 3'UTR, however, how SIRT7 gene is regulated remains unclear. Here, we identified the transcription initiation site of human SIRT7 gene at the upstream 23rd A nucleotide respective to the translational codon, and the SIRT7 is a TATA-less and initiator-less gene. The sequences in the upstream region between -256 and -129 bp are identical with important functions in the three species detected. A C/EBPα responding element is found that binds both C/EBPα and C/EBPß in vitro. We showed TSA induced SIRT7 gene transcription and only the HDAC3, but not its catalytic domain depleted mutant, interacted with C/EBPα to occupy the C/EBPα element and repressed SIRT7 gene in the hepatocellular carcinoma cells. To our knowledge, this is the first report on the regulation mechanism of SIRT7 gene, in which, HDAC3 collaborated with C/EBPα to occupy its responding element in the upstream region of SIRT7 gene and repressed its expression in human cells.

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Benzo[a]pyrene (B[a]P) is a carcinogen in cigarette smoke. We found that B[a]P induced SIRT1 in human bronchial epithelial BEAS-2B cell. SIRT1 was overexpressed in the lung of B[a]P-exposed mice and in human lung cancer biopsies. SIRT1 up-regulated TNF-α and ß-catenin and down-regulated the membrane fraction of E-cadherin. In addition, SIRT1 promoted invasion, migration and tumorigenesis of BEAS-2B cells in nude mice upon B[a]P exposure. Thus, SIRT1 is involved in B[a]P-induced transformation associated with activation of the TNF-α/ß-catenin axis and is as a potential therapeutic target for lung cancer.

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Tuberculous pleural effusion is the second most common form of extrapulmonary tuberculosis, which is very difficult to rapidly distinguish from malignant pleural effusion in the clinical setting. A time-resolved fluoroimmunoassay (TRF) of CFP-10, a low molecular weight protein secreted by pathogenic Mycobacterium tuberculosis, was developed to differentiate tuberculous pleural effusion from malignant one. The measuring range was 0.3-187.5 ng/ml with the dose-response coefficient of 0.9998 and detection limit of 0.036 ng/ml. The intra-assay and inter-assay coefficients of variation were 3.6-9.2% and 10.0-12.4%, respectively. The concentration of CFP-10 in malignant pleural effusion was less than 0.8 ng/ml. The negative predictive value was 93.1% in malignant pleural effusion (n = 247) while the positive predictive value was 83.0% in tuberculous pleural effusion (n = 235). Moreover, there was a statistically significant difference in the CFP-10 concentration of pleural effusion between the groups before and after clinical therapy of tuberculosis (P < 0.001, n = 81). In addition, the stability of the diagnostic reagents lasted at least 1 year at 4 °C. Therefore, the TRF of CFP-10 may be used for the rapid diagnosis of tuberculous pleural effusion and further monitoring the clinical therapeutic efficacy of tuberculosis.

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KrF excimer laser precision machining of porous hard-brittle ceramic biomaterials was studied to find a suitable way of machining the materials into various desired shapes and sizes without distorting their intrinsic structure and porosity. Calcium phosphate glass ceramics (CPGs) and hydroxyapatite (HA) were chosen for the study. It was found that KrF excimer laser can cut both CPGs and HA with high efficiency and precision. The ablation rates of CPGs and HA are respectively 0.081 µm/(pulse J cm(-2)) and 0.048 µm/(pulse J cm(-2)), while their threshold fluences are individually 0.72 and 1.5 J cm(-2). The cutting quality (smoothness of the cut surface) is a function of laser repetition rate and cutting speed. The higher the repetition rate and lower the cutting speed, the better the cutting quality. A comparison between the cross sections of CPGs and HA cut using the excimer laser and using a conventional diamond cutting blade indicates that those cut by the excimer laser could retain their intrinsic porosity and geometry without distortion. In contrast, those cut by conventional machining had distorted geometry and most of their surface porosities were lost. Therefore, when cutting hard-brittle ceramic biomaterials to prepare scaffold and implant or when sectioning them for porosity evaluation, it is better to choose KrF excimer laser machining.

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Particulate matter (PM) has been becoming the principal urban pollutant in many major cities in China, and even all over the world. It is reported that the coal combustion process is one of the main sources of PM in the atmosphere. Therefore, an investigation of formation and emission of fine primary PM in coal combustion was conducted. First, the sources and classification of coal-fired primary PM were discussed; then their formation pathways during the coal combustion process were analyzed in detail. Accordingly, the emission control methods for fine particles generated from coal-fired power plants were put forward, and were classified as precombustion control, in-combustion control, and postcombustion control. Precombustion control refers to the processes for improving the coal quality before combustion, such as coal type selection and coal preparation. In-combustion control means to take measures for adjusting the combustion conditions and injection of additives during the combustion process to abate the formation of PM. Postcombustion control is the way that the fine PM are aggregated into larger ones by some agglomeration approaches and subsequently are removed by dust removal devices, or some high-performance modifications of conventional particle emission control devices (PECDs) can be taken for capturing fine particles. Finally, some general management suggestions are given for reducing fine PM emission in coal-fired power plants. Implications: The analysis and discussions of coal properties and its combustion process are critical to recognizing the formation and emission of the fine primary PM in combustion. The measures of precombustion, in-combustion, and postcombustion control based on the analysis and discussions are favorable for abating the PM emission. Practically, some measures of implementation do need the support of national policies, even needing to sacrifice economy to gain environmental profit, but this is the very time to execute these, and high-performances PECDs, especially novel devices, should be used for removing fine PM in flue gas.

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Growth arrest and DNA damage (GADD) 45α is a member of GADD inducible gene family, and is inducible in cell response to oxidative stress. GADD45α upregulation induces MKK4/JNK activation in some published experimental systems. However, we found here that the depletion of GADD45α (GADD45α-/-) in mouse embryonic fibroblasts (MEFs) resulted in an increase in the phosphorylation of MKK4/7, MKK3/6 and consequently specific up-regulated the activation of JNK/p38 and their downstream transcription factors, such as c-Jun and ATF2, in comparison to those in GADD45α+/+ MEFs cell following nickel exposure. This up-regulation of MKK-JNK/p38 pathway in GADD45α-/- cell could be rescued by the reconstitutional expression of HA-GADD45α in GADD45α-/- MEFs, GADD45α-/-(HA-GADD45α). Subsequent studies indicated that GADD45α deletion repressed expression of PP2Cα, the phosphotase of MKK3/6 and MKK4/7, whereas ectopic expression of HA-PP2Cα in GADD45α-/- cells attenuated activation of MKK3/6-p38 and MKK4/7-JNK pathways. Collectively, our results demonstrate a novel function and mechanism responsible for GADD45α regulation of MKK/MAPK pathway, further provides insight into understanding the big picture of GADD45α in the regulation of cellular responses to oxidative stress and environmental carcinogens.

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Covalent modifications of histone tails have fundamental roles in chromatin structure and function. Tri-methyl modification on lysine 27 of histone H3 (H3K27me3) usually correlates with gene repression that plays important roles in cell lineage commitment and development. Mash1 is a basic helix-loop-helix regulatory protein that plays a critical role in neurogenesis, where it expresses as an early marker. In this study, we have shown a decreased H3K27me3 accompanying with an increased demethylase of H3K27me3 (Jmjd3) at the promoter of Mash1 can elicit a dramatically efficient expression of Mash1 in RA-treated P19 cells. Over-expression of Jmjd3 in P19 cells also significantly enhances the RA-induced expression and promoter activity of Mash1. By contrast, the mRNA expression and promoter activity of Mash1 are significantly reduced, when Jmjd3 siRNA or dominant negative mutant of Jmjd3 is introduced into the P19 cells. Chromatin immunoprecipitation assays show that Jmjd3 is efficiently recruited to a proximal upstream region of Mash1 promoter that is overlapped with the specific binding site of Hes1 in RA-induced cells. Moreover, the association between Jmjd3 and Hes1 is shown in a co-Immunoprecipitation assay. It is thus likely that Jmjd3 is recruited to the Mash1 promoter via Hes1. Our results suggest that the demethylase activity of Jmjd3 and its mediator Hes1 for Mash1 promoter binding are both required for Jmjd3 enhanced efficient expression of Mash1 gene in the early stage of RA-induced neuronal differentiation of P19 cells.

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