Utilizing sludge-based activated carbon for targeted leachate mitigation in wastewater treatment.

Activated carbon (AC) based adsorbents derived from waste sludge were utilized to remediate mixed contaminants in wastewater as an integrated waste-to-resource approach promoting a paradigm shift in management of refuse sludge and wastewater. This review specifically focuses on the remediation of constituents of landfill leachate by sludge-based activated carbon (SBAC). The adsorption effectiveness of SBAC for the exclusion of leachate characters including heavy metals, phenols, dyes, phosphates, and phosphorus were explored with regard to modifiers such as pH, temperature, properties of the adsorbent including functional groups, initial doses of absorbent and adsorbate, and duration of exposure to note the impact of each parameter on the efficiency of adsorption of the sludge adsorbent. Through the works of various researchers, it was noted that the properties of the adsorbent, pH and temperature impact the working of SBACs. The pH of the adsorbent by influencing the functional groups. Temperature was expected to have a paramount effect on the adsorption efficiency of the SBACs. The importance of the regeneration and recycling of the adsorbents as well as their leachability is highlighted. Sludge based activated carbon is recommended as a timely, resource-efficient, and sustainable approach for the remediation of wastewater.

Recovery of non-metallic useable materials from e-waste.

Tremendous amounts of electric and electronic wastes (e-waste) are generated daily, and their indiscriminate disposal may cause serious environmental pollution. The recovery of non-metallic materials from e-waste is a strategy to not only reduce the volume of e-waste but also avoid pollutant emissions produced by indiscriminate disposal of e-waste. Pyrolysis, sub/supercritical water treatment, chemical dissolution, and physical treatment (e.g., ball milling, flotation, and electrostatic separation) are available methods to recover useable non-metallic materials (e.g., resins, fibers, and various kinds of polymers) from e-waste. The e-waste-derived materials can be used to manufacture a large variety of industrial and consumer products. In this regard, this work attempts to compile relevant knowledge on the technologies that derive utilizable materials from different classes of e-waste. Moreover, this work highlights the potential of the e-waste-derived materials for various applications. Current challenges and perspectives on e-waste upcycling to useable materials are also discussed.

Enhanced mono-aromatics production by the CH4-assisted pyrolysis of microalgae using Zn-based HZSM-5 catalysts.

This study presents the catalytic pyrolysis of microalgae, Chlorella vulgaris (C. vulgaris), using pure CH4 and H2-rich gas evolved from CH4 decomposition on three different HZSM-5 catalysts loaded with Zn, Ga, and Pt, aimed specifically at producing high-value mono-aromatics such as benzene, toluene, ethylbenzene, and xylene (BTEX). In comparison with that for the typical inert N2 environment, a pure CH4 environment increased the bio-oil yield from 32.4 wt% to 37.4 wt% probably due to hydrogen and methyl radical insertion in the bio-oil components. Furthermore, the addition of bimetals further increased bio-oil yield. For example, ZnPtHZ led to a bio-oil yield of 47.7 wt% in pure CH4. ZnGaHZ resulted in the maximum BTEX yield (6.68 wt%), which could be explained by CH4 activation, co-aromatization, and hydrodeoxygenation. The BTEX yield could be further increased to 7.62 wt% when pyrolysis was conducted in H2-rich gas evolved from CH4 decomposition over ZnGaHZ, as rates of aromatization and hydrodeoxygenation were relatively high under this condition. This study experimentally validated that the combination of ZnGaHZ and CH4 decomposition synergistically increases BTEX production using C. vulgaris.

Fractional condensation of bio-oil vapors from pyrolysis of various sawdust wastes in a bench-scale bubbling fluidized bed reactor.

The use of lignocellulosic waste as an energy source for substituting fossil fuels has attracted lots of attention, and pyrolysis has been established as an effective technology for this purpose. However, the utilization of bio-oil derived from non-catalytic pyrolysis faces certain constraints, making it impractical for direct application in advanced sectors. This study has focused on overcoming these challenges by employing fractional condensation of pyrolytic vapors at distinct temperatures. The potential of five types of sawdust for producing high-quality bio-oil through pyrolysis conducted with a bench-scale bubbling fluidized bed reactor was investigated for the first time. The highest yield of bio-oil (61.94 wt%) was produced using sample 3 (damaged timber). Remarkably, phenolic compounds were majorly gathered in the 1st and 2nd condensers at temperatures of 200 °C and 150 °C, respectively, attributing to their higher boiling points. Whereas, carboxylic acid, ketones, and furans were mainly collected in the 3rd (-5 °C) and 4th (-20 °C) condensers, having high water content in the range of 35.33%-65.09%. The separation of acidic nature compounds such as acetic acid in the 3rd and 4th was evidenced by its low pH in the range of 4-5, while the pH of liquid collected in the 1st and 2nd condensers exhibited higher pH (6-7). The well-separated bio-oil derived from biomass pyrolysis facilitates its wide usage in various applications, proposing a unique approach toward carbon neutrality. In particular, achieving efficient separation of phenolic compounds in bio-oil is important, as these compounds can undergo further upgrading to generate hydrocarbons and diesel fuel.

Recent advances in liquid fuel production from plastic waste via pyrolysis: Emphasis on polyolefins and polystyrene.

The management of plastic waste (PW) has become an indispensable worldwide issue because of the enhanced accumulation and environmental impacts of these waste materials. Thermo-catalytic pyrolysis has been proposed as an emerging technology for the valorization of PW into value-added liquid fuels. This review provides a comprehensive investigation of the latest advances in thermo-catalytic pyrolysis of PW for liquid fuel generation, by emphasizing polyethylene, polypropylene, and polystyrene. To this end, the current strategies of PW management are summarized. The various parameters affecting the thermal pyrolysis of PW (e.g., temperature, residence time, heating rate, pyrolysis medium, and plastic type) are discussed, highlighting their significant influence on feed reactivity, product yield, and carbon number distribution of the pyrolysis process. Optimizing these parameters in the pyrolysis process can ensure highly efficient energy recovery from PW. In comparison with non-catalytic PW pyrolysis, catalytic pyrolysis of PW is considered by discussing mechanisms, reaction pathways, and the performance of various catalysts. It is established that the introduction of either acid or base catalysts shifts PW pyrolysis from the conventional free radical mechanism towards the carbonium ion mechanism, altering its kinetics and pathways. This review also provides an overview of PW pyrolysis practicality for scaling up by describing techno-economic challenges and opportunities, environmental considerations, and presenting future outlooks in this field. Overall, via investigation of the recent research findings, this paper offers valuable insights into the potential of thermo-catalytic pyrolysis as an emerging strategy for PW management and the production of liquid fuels, while also highlighting avenues for further exploration and development.

Advancements in TiO2-based photocatalysis for environmental remediation: Strategies for enhancing visible-light-driven activity.

Researchers have focused on efficient techniques for degrading hazardous organic pollutants due to their negative impacts on ecological systems, necessitating immediate remediation. Specifically, TiO2-based photocatalysts, a wide-bandgap semiconductor material, have been extensively studied for their application in environmental remediation. However, the extensive band gap energy and speedy reattachment of electron (e-) and hole (h+) pairs in bare TiO2 are considered major disadvantages for photocatalysis. This review extensively focuses on the combination of semiconducting photocatalysts for commercial outcomes to develop efficient heterojunctions with high photocatalytic activity by minimizing the e-/h+ recombination rate. The improved activity of these heterojunctions is due to their greater surface area, rich active sites, narrow band gap, and high light-harvesting tendency. In this context, strategies for increasing visible light activity, including doping with metals and non-metals, surface modifications, morphology control, composite formation, heterojunction formation, bandgap engineering, surface plasmon resonance, and optimizing reaction conditions are discussed. Furthermore, this review critically assesses the latest developments in TiO2 photocatalysts for the efficient decomposition of various organic contaminants from wastewater, such as pharmaceutical waste, dyes, pesticides, aromatic hydrocarbons, and halo compounds. This review implies that doping is an effective, economical, and simple process for TiO2 nanostructures and that a heterogeneous photocatalytic mechanism is an eco-friendly substitute for the removal of various pollutants. This review provides valuable insights for researchers involved in the development of efficient photocatalysts for environmental remediation.

Production of light olefins and monocyclic aromatic hydrocarbons from the pyrolysis of waste plastic straws over high-silica zeolite-based catalysts.

Owing to the ever-increasing generation of plastic waste, the need to develop environmentally friendly disposal methods has increased. This study explored the potential of waste plastic straw to generate valuable light olefins and monocyclic aromatic hydrocarbons (MAHs) via catalytic pyrolysis using high-silica zeolite-based catalysts. HZSM-5 (SiO2/Al2O3:200) exhibited superior performance, yielding more light olefins (49.8 wt%) and a higher MAH content than Hbeta (300). This was attributed to the increased acidity and proper shape selectivity. HZSM-5 displayed better coking resistance (0.7 wt%) than Hbeta (4.4 wt%) by impeding secondary reactions, limiting coke precursor formation. The use of HZSM-5 (80) resulted in higher MAHs and lower light olefins than HZSM-5 (200) because of its higher acidity. Incorporation of Co into HZSM-5 (200) marginally lowered light olefin yield (to 44.0 wt%) while notably enhancing MAH production and boosting propene selectivity within the olefin composition. These observations are attributed to the well-balanced coexistence of Lewis and Brønsted acid sites, which stimulated the carbonium ion mechanism and induced H-transfer, cyclization, Diels-alder, and dehydrogenation reactions. The catalytic pyrolysis of plastic straw over high-silica and metal-loaded HZSM-5 catalysts has been suggested as an efficient and sustainable method for transforming plastic waste materials into valuable light olefins and MAHs.

A comprehensive study of artificial neural network for sensitivity analysis and hazardous elements sorption predictions via bone char for wastewater treatment.

Using bone char for contaminated wastewater treatment and soil remediation is an intriguing approach to environmental management and an environmentally friendly way of recycling waste. The bone char remediation strategy for heavy metal-polluted wastewater was primarily affected by bone char characteristics, factors of solution, and heavy metal (HM) chemistry. Therefore, the optimal parameters of HM sorption by bone char depend on the research being performed. Regarding enhancing HM immobilization by bone char, a generic strategy for determining optimal parameters and predicting outcomes is crucial. The primary objective of this research was to employ artificial neural network (ANN) technology to determine the optimal parameters via sensitivity analysis and to predict objective function through simulation. Sensitivity analysis found that for multi-metals sorption (Cd, Ni, and Zn), the order of significance for pyrolysis parameters was reaction temperature > heating rate > residence time. The primary variables for single metal sorption were solution pH, HM concentration, and pyrolysis temperature. Regarding binary sorption, the incubation parameters were evaluated in the following order: HM concentrations > solution pH > bone char mass > incubation duration. This approach can be used for further experiment design and improve the immobilization of HM by bone char for water remediation.

Catalytic pyrolysis of harmful plastic waste to alleviate environmental impacts.

Wax is a detrimental byproduct of plastic waste pyrolysis causing challenges upon its release into the environment owing to persistence and potential toxicity. In this study, the valorization of wax materials through conversion into BTEX (i.e., benzene, toluene, ethylbenzene, and xylene) was achieved via catalytic pyrolysis using zeolite-based catalysts. The potential of two types of waxes, spent wax (SW), derived from the pyrolysis of plastic waste, and commercial paraffin wax (PW), for BTEX generation, was investigated. Using HZSM-5, higher yields of oil (54.9 wt%) and BTEX (18.2 wt%) were produced from the pyrolysis of SW compared to PW (32.3 and 14.1 wt%, respectively). This is due to the improved accessibility of lighter hydrocarbons in SW to Brønsted and Lewis acid sites in HZSM-5 micropores, promoting cracking, isomerization, cyclization, Diels-Alder, and dehydrogenation reactions. Further, the use of HZSM-5 resulted in significantly larger yields of oil and BTEX from SW pyrolysis compared to Hbeta and HY. This phenomenon is ascribed to the well-balanced distribution of Brønsted and Lewis acid sites and the identical geometric structure of HZSM-5 micropores and BTEX molecules. The addition of Ga to HZSM-5 further led to 2.24% and 28.30% enhancements in oil and BTEX yields, respectively, by adjusting the acidity of the catalyst through the introduction of new Lewis acid sites. The regeneration of the Ga/HZSM-5 catalyst by removing deposited coke on the spent catalyst under air partially recovered catalytic activity. This study not only offers an efficient transformation of undesirable wax into valuable fuels but also provides an environmentally promising solution, mitigating pollution, contributing to carbon capture, and promoting a healthier and more sustainable environment. It also suggests future research directions, including catalyst optimization and deactivation management, feedstock variability exploration, and techno-economic analyses for sustainable wax conversion into BTEX via catalytic pyrolysis.

An overview of commercialization and marketization of thermoelectric generators for low-temperature waste heat recovery.

According to statistics, low-temperature waste heat below 300°C accounts for more than 89% of industrial waste heat. If the waste heat is not recycled, a large amount of low-temperature waste heat will be released into the atmosphere, thereby exacerbating global warming and posing a significant threat to human survival. Although the power generation efficiency of solid-state thermoelectric generation technology is lower than the organic Rankine cycle, it only requires a smaller construction area, which increases its market acceptance, applicability, and penetration. Especially in the pursuit of net-zero emissions by global companies, the importance of low-temperature waste heat recovery and power generation is even more prominent. The current thermoelectric conversion efficiency of commercial thermoelectric chips is about 5%. Power generation cost, thermoelectric conversion efficiency, and energy use efficiency are highly correlated with the commercialization of solid-state thermoelectric technology. This research shares five practical waste heat power generation cases commercialized by recycling three heat sources. It also points out the three significant challenges facing the commercialization of power generation from low-temperature waste heat recovery. This study analyzes 2,365 TEG patents submitted by 28 companies worldwide to determine the basic technology for realizing waste heat recovery through TEG and explore the potential commercialization of related waste heat recovery products. The future challenge for the large-scale commercialization of solid-state thermoelectric technology is not technological development but financial incentives related to changes in international energy prices and subsidies that promote zero carbon emissions.

Development of novel recombinant peroxidase secretion system from Pseudomonas putida for lignin valorisation.

Pseudomonas putida is a promising strain for lignin valorisation. However, there is a dearth of stable and efficient systems for secreting enzymes to enhance the process. Therefore, a novel secretion system for recombinant lignin-depolymerising peroxidase was developed. By adopting a flagellar type III secretion system, P. putida KT-M2, a secretory host strain, was constructed and an optimal secretion signal fusion partner was identified. Application of the dye-decolourising peroxidase of P. putida to this system resulted in efficient oxidation activity of the cell-free supernatant against various chemicals, including lignin model compounds. This peroxidase-secreting strain was examined to confirm its lignin utilisation capability, resulting in the efficient assimilation of various lignin substrates with 2.6-fold higher growth than that of the wild-type strain after 72 h of cultivation. Finally, this novel system will lead efficient bacterial lignin breakdown and utilization through enzyme secretion, paving the way for sustainable lignin-consolidated bioprocessing.

Recent strategies for neural dynamics observation at a larger scale and wider scope.

The tremendous technical progress in neuroscience offers opportunities to observe a more minor or/and broader dynamic picture of the brain. Moreover, the large-scale neural activity of individual neurons enables the dissection of detailed mechanistic links between neural populations and behaviors. To measure neural activity in-vivo, multi-neuron recording, and neuroimaging techniques are employed and developed to acquire more neurons. The tools introduced concurrently recorded dozens to hundreds of neurons in the coordinated brain regions and elucidated the neuronal ensembles from a massive population perspective of diverse neurons at cellular resolution. In particular, the increasing spatiotemporal resolution of neuronal monitoring across the whole brain dramatically facilitates our understanding of additional nervous system functions in health and disease. Here, we will introduce state-of-the-art neuroscience tools involving large-scale neural population recording and the long-range connections spanning multiple brain regions. Their synergic effects provide to clarify the controversial circuitry underlying neuroscience. These challenging neural tools present a promising outlook for the fundamental dynamic interplay across levels of synaptic cellular, circuit organization, and brain-wide. Hence, more observations of neural dynamics will provide more clues to elucidate brain functions and push forward innovative technology at the intersection of neural engineering disciplines. We hope this review will provide insight into the use or development of recent neural techniques considering spatiotemporal scales of brain observation.

Investigating catalytic oxidative desulfurization of model fuel using hollow PW12/TiO2@MgCO3 and performance optimization via box-behnken design.

A facile and eco-friendly synthesis of PW12/TiO2@MgCO3 hollow tubes (PW12·âˆ¼· H3[PW12O40] = polyoxometalate) using a soluble and reusable MgCO3·3H2O micro-rods template was reported for the first time. The resultant hollow tubes were characterized by Fourier transform infrared spectroscopy (FT-IR), UV-visible spectroscopy, powder X-ray diffraction (PXRD), energy-dispersive X-ray spectroscopy (EDX), and scanning electron microscopy (SEM), which indicated that the [PW12O40]3- structure remained intact within the hollow tubes. Furthermore, the specific surface area (88.982 m2/g) and average pore size (2.6 nm) of the PW12/TiO2@MgCO3 hollow tubes were calculated using the Brunauer-Emmett-Teller (BET) analysis. This study explored the catalytic performance of PW12/TiO2@MgCO3 hollow tubes using a three-level Box-Behnken design (BBD), through which optimization curves were designed. The desulfurization of model fuel using hollow tubes was optimally performed when the catalyst dose, time, temperature, and oxidant/sulfur (O/S) were 20-80 gm, 80-120 min, 25-80 °C and 3-8 molar ratio, respectively. These results were further processed, and the experiments were replicated twenty-nine times using a model based on two quadratic polynomials to create a response surface methodology (RSM). This permits a mathematical correlation linking the desulfurization and experimental parameters. The optimal performance of reaction mixture was evaluated to be 80 mg for catalyst concentration, 25 °C of temperature, reaction time of 100 min, and 5.5 for oxidant/sulfur molar ratio from 20 mL of octane simulation oil containing 350 ppm dibenzothiophene (DBT). The predicted desulfurization rate of the model fuel under these optimal conditions was 95.3%. The correspondence between the experimental results and predicted values was verified based on regression analysis, with an R2 value greater than 0.99. These hollow tubes could be used for their desulfurization properties ten times a row without significantly reducing catalytic activity.

Reduction of odor-causing compounds in wastewater using biochar: A review.

Wastewater contains chemical compounds that cause malodors, such as ammonium cation, dimethyl sulfide, and volatile organic compounds. Biochar-based reduction in the odorants has been proposed as an effective approach along with maintaining environmental neutrality as biochar is a sustainable material made from biomass and biowaste. Biochar can have high specific surface area and microporous structure with proper activation, appropriate for sorption purposes. Recently, various research directions have been proposed to determine the removal efficiency of biochar for different odorants contained in wastewater. This article is aimed at providing the most updated review of biochar-based removal of odor-causing compounds in wastewater while highlighting the current advances. It was distinguished that the odorant removal performance of biochar is highly associated with the raw material and modification method of biochar, and the kind of odorants. Further research should be required for more practical use of biochar for the reduction of odorants in wastewater.

Mitigation of N2O emissions via enhanced denitrification in a biological landfill leachate treatment using external carbon from fermented sludge.

The effects of an external carbon source (C-source) on the mitigation of N2O gas (N2O(g)) emissions from landfill leachate were investigated via enhanced denitrification using anaerobically fermented sewage sludge. Anaerobic fermentation of sewage sludge was conducted under thermophilic conditions with progressively increasing organic loading rates (OLR). Optimal conditions for fermentation were determined based on the efficiency of hydrolysis and the concentrations of sCOD and volatile fatty acids (VFAs) as follows: at an OLR of 40.48 ± 0.77 g COD/L·d with 1.5 days of solid retention time (SRT), 14.68 ± 0.59% of efficiency of hydrolysis, 14.42 ± 0.30 g sCOD/L and 7.85 ± 0.18 g COD/L of VFAs. Analysis of the microbial community in the anaerobic fermentation reactor revealed that degradation of sewage sludge might be potentially affected by proteolytic microorganisms producing VFAs from proteinaceous materials. Sludge-fermentate (SF) retrieved from the anaerobic fermentation reactor was used as the external C-source for denitrification testing. The specific nitrate removal rate (KNR) of the SF-added condition was 7.54 mg NO3-N/g VSS·hr, which was 5.42 and 2.43 times higher than that of raw landfill leachate (LL) and a methanol-added condition, respectively. In the N2O(g) emission test, the liquid phase N2O (N2O-N(l)) of 20.15 mg N/L was emitted as N2O(g) of 19.64 ppmv under only LL-added condition. On the other hand, SF led to the specific N2O(l) reduction rate (KN2O) of 6.70 mg N/g VSS hr, resulting in mitigation of 1.72 times the N2O(g) emission compared to under the only-LL-added condition. The present study revealed that N2O(g) emissions from biological landfill leachate treatment plants can be attenuated by simultaneous reduction of NO3-N and N2O(l) during enhanced denitrification via a stable supply of an external C-source retrieved from anaerobically fermented organic waste.

Erratum: Correction of Authors in the Article "Relevance Index Regional Variation by Each Disease and Its Essential Medical Field: A Retrospective Data Analysis From 2016-2020 in Korea".

This corrects the article on p. e130 in vol. 38, PMID: 37096313.

Oxidative torrefaction of microalgae Chlorella sorokiniana: Process optimization by central composite design.

Microalgae are currently not viable as solid biofuels owing to their poor raw fuel properties. Torrefaction under oxidative media offers a cost-effective and energy-efficient process to address these drawbacks. A design of experiment was conducted using central composite design with three factors: temperature (200, 250, and 300 °C), time (10, 35, and 60 min), and O2 concentration (3, 12, and 21 vol%). The responses were solid yield, energy yield, higher heating value, and onset temperatures at 50% and 90% carbon conversion determined from thermogravimetric analysis. Temperature and time significantly affected all responses, while O2 concentration only affected higher heating value, energy yield and thermodegradation temperature at 90% conversion. Oxidative torrefaction of microalgae is recommended to be conducted at 200 °C, 10.6 min, 12% O2 where the energy yield and enhancement factor are 98.73% and 1.08, respectively. It is also more reactive under an air environment compared to inert torrefaction conditions.

Relevance Index Regional Variation by Each Disease and Its Essential Medical Field: A Retrospective Data Analysis From 2016-2020 in Korea.

BACKGROUND: To precisely build a healthcare delivery system at regional levels, local patients' healthcare service utilization patterns must be examined. Hence, this study utilized trend analysis of the relevance index of each disease of each essential medical service field at the municipal and provincial levels. METHODS: This study analyzed customized databases released by the National Health Insurance Service from 2016-2020. Diseases defined in the Korean National Burden of Disease (KNBD) study were categorized into the following essential medical service fields: trauma care, cardiocerebrovascular, maternal and neonatal, mental health, infection, cancer, older adults' care and rehabilitation, and others. Relevance index, the percentage of medical service utilization in a region by the residents of that region relative to their total medical service utilization, was examined by region (17 municipal and provincial regions) and disease area. The relevance index was determined based on the number of patients and the total out-of-pocket expenses. RESULT: Eight of the 17 regions showed over a 90.0% relevance index in the infection area. In the cancer area, 14 regions (not including Seoul, Daegu, and Busan) had a relevance index lower than 75.0%. Throughout the analysis period (2016-2020), there were no significant variations in the relevance index. Diseases such as bone and connective tissue cancer (39.0%), neural tube defects (16.7%), and autism (57.1%) had low relevance index in the essential medical service fields. In all 17 regions, the relevance index of inpatients was lower than that of outpatients, and that for out-of-pocket expenses was lower than that based on the number of patients. CONCLUSION: The relevance index of major diseases of each essential medical service field calculated in this study can provide good indicators for monitoring the level of an independent regional healthcare delivery system.

MLL3/MLL4 methyltransferase activities control early embryonic development and embryonic stem cell differentiation in a lineage-selective manner.

H3K4me1 methyltransferases MLL3 (KMT2C) and MLL4 (KMT2D) are critical for enhancer activation, cell differentiation and development. However, roles of MLL3/4 enzymatic activities and MLL3/4-mediated enhancer H3K4me1 in these processes remain unclear. Here we report that constitutive elimination of both MLL3 and MLL4 enzymatic activities prevents initiation of gastrulation and leads to early embryonic lethality in mice. However, selective elimination of MLL3/4 enzymatic activities in embryonic, but not extraembryonic, lineages leaves gastrulation largely intact. Consistent with this, embryonic stem cells (ESCs) lacking MLL3/4 enzymatic activities can differentiate toward the three embryonic germ layers but show aberrant differentiation to extraembryonic endoderm (ExEn) and trophectoderm. The failure in ExEn differentiation can be attributed to markedly reduced enhancer-binding of the lineage-determining transcription factor GATA6. Furthermore, we show that MLL3/4-catalyzed H3K4me1 is largely dispensable for enhancer activation during ESC differentiation. Together, our findings suggest a lineage-selective, but enhancer activation-independent, role of MLL3/4 methyltransferase activities in early embryonic development and ESC differentiation.