The methyltransferase like 3 (METTL3) has been generally recognized as a nuclear protein bearing oncogenic properties. We find predominantly cytoplasmic METTL3 expression inversely correlates with ...node metastasis in human cancers. It remains unclear if nuclear METTL3 is functionally distinct from cytosolic METTL3 in driving tumorigenesis and, if any, how tumor cells sense oncogenic insults to coordinate METTL3 functions within these intracellular compartments. Here, we report an acetylation-dependent regulation of METTL3 localization that impacts on metastatic dissemination. We identify an IL-6-dependent positive feedback axis to facilitate nuclear METTL3 functions, eliciting breast cancer metastasis. IL-6, whose mRNA transcript is subjected to METTL3-mediated m
A modification, promotes METTL3 deacetylation and nuclear translocation, thereby inducing global m
A abundance. This deacetylation-mediated nuclear shift of METTL3 can be counterbalanced by SIRT1 inhibition, a process that is further enforced by aspirin treatment, leading to ablated lung metastasis via impaired m
A methylation. Intriguingly, acetylation-mimetic METTL3 mutant reconstitution results in enhanced translation and compromised metastatic potential. Our study identifies an acetylation-dependent regulatory mechanism determining the subcellular localization of METTL3, which may provide mechanistic clues for developing therapeutic strategies to combat breast cancer metastasis.
Aberrant transcripts expression of the m
A methyltransferase complex (MTC) is widely found across human cancers, suggesting a dysregulated signaling cascade which integrates m
A epitranscriptome to ...drive tumorigenesis. However, the responsible transcriptional machinery directing the expression of distinct MTC subunits remains unclear. Here, we identified an unappreciated interplay between the histone acetyl-lysine reader BRD4 and the m
A writer complex across human cancers. BRD4 directly stimulates transcripts expression of seven MTC subunits, allowing the maintenance of the nuclear writer complex integrity. Upon BET inhibition, this BRD4-MTC signaling cascade accounts for global m
A reduction and the subsequent dynamic alteration of BRD4-dependent transcriptome, resulting in impaired DNA damage response that involves activation of homologous recombination (HR) repair and repression of apoptosis. We further demonstrated that the combined synergy upon BET/PARP inhibition largely relies on disrupted m
A modification of HR and apoptotic genes, counteracting PARP inhibitor (PARPi) resistance in patient-derived xenograft models. Our study revealed a widespread active cross-talk between BRD4-dependent epigenetic and MTC-mediated epitranscriptomic networks, which provides a unique therapeutic vulnerability that can be leveraged in combined DNA repair-targeted therapy.
Aberrant transcripts expression of the m6A methyltransferase complex (MTC) is widely found across human cancers, suggesting a dysregulated signaling cascade which integrates m6A epitranscriptome to ...drive tumorigenesis. However, the responsible transcriptional machinery directing the expression of distinct MTC subunits remains unclear. Here, we identified an unappreciated interplay between the histone acetyl-lysine reader BRD4 and the m6A writer complex across human cancers. BRD4 directly stimulates transcripts expression of seven MTC subunits, allowing the maintenance of the nuclear writer complex integrity. Upon BET inhibition, this BRD4-MTC signaling cascade accounts for global m6A reduction and the subsequent dynamic alteration of BRD4-dependent transcriptome, resulting in impaired DNA damage response that involves activation of homologous recombination (HR) repair and repression of apoptosis. We further demonstrated that the combined synergy upon BET/PARP inhibition largely relies on disrupted m6A modification of HR and apoptotic genes, counteracting PARP inhibitor (PARPi) resistance in patient-derived xenograft models. Our study revealed a widespread active cross-talk between BRD4-dependent epigenetic and MTC-mediated epitranscriptomic networks, which provides a unique therapeutic vulnerability that can be leveraged in combined DNA repair-targeted therapy.
Polymer solar cells have the potential to become a major electrical power generating tool in the 21st century. R&D endeavors are focusing on continuous roll-to-roll printing of polymeric or organic ...compounds from solutionlike newspapersto produce flexible and lightweight devices at low cost. It is recognized, though, that besides the functional properties of the compounds the organization of structures on the nanometer levelforced and controlled mainly by the processing conditions applieddetermines the performance of state-of-the-art polymer solar cells. In such devices the photoactive layer is composed of at least two functional materials that form nanoscale interpenetrating phases with specific functionalities, a so-called bulk heterojunction. In this perspective article, our current knowledge on the main factors determining the morphology formation and evolution is introduced, and gaps of our understanding on nanoscale structure−property relations in the field of high-performance polymer solar cells are addressed. Finally, promising routes toward formation of tailored morphologies are presented.
•Sand blocks can be cemented by seawater based MICP.•The urease activity in the seawater based UPB was measured.•Building materials can be prepared by the seawater based MICP.•One/two-phase seawater ...based MICP was compared.•Biocementation sand blocks of mechanism was analyzed and discussed.
The Sporosarcina pasteurii strains can grow and multiply in seawater medium and have certain urease activity. The two-phase and one-phase cementation methods can be used for the construction of ocean islands and reefs far away from the mainland in seawater seawater based MICP (Microbial-Induced Carbonate Precipitation). The compressive strength, carbonates content and porosity of sand blocks cemented by seawater based MICP with two-phase and one-phase methods are measured and compared. The results show that the strength and carbonates content of sand blocks with two-phase biocementation are greater than that of one-phase. The SEM images show that the principle of seawater based MICP cementing loose sand blocks is that carbonates particles grow between the sand particles, and them act as a bridge to bind the loose sand particles into a whole. The seawater based UPB of different pH can induce calcium carbonate deposition at different time. The seawater based UPB of different pH can be selected according to the actual project to reinforce the island reef sand foundation and prepare building materials under one-phase biocementation.
This paper reports a mixture based on the calcium carbide sludge (CCS) activation of fly ash. The formed calcium silicate hydrate (C–S–H) gel binds sands and gravel particles to synthesize ...pozzolanic-lime mortars and concretes. In both seawater and tap water, Ca(CO3), Ca(OH)2, and C–S–H were the main phases of hydration, as determined by powder X-ray diffraction. The optimal mixture was obtained using a CCS to FA ratio of 0.8 and curing time of 14 d. The surface morphology of spherical FA in the tap water mixed pozzolanic-lime materials had relatively loose rod-like, flower-like, and block structures, which were different from the irregular and dense block structure in the seawater mixed pozzolanic-lime mixture. For the fiber-reinforced mortar, the optimal content of polypropylene fiber was 0.1%. The surfaces of the fiber reinforced pozzolanic-lime mortars prepared using seawater were more compact than those prepared using tap and distilled water. The strengths of the fiber-reinforced specimens soaked in both seawater and tap water were maintained after 14, 28, 60, 90, and 120 d. The water permeability of pozzolanic-lime mixture with cracks was effectively reduced by spraying a seawater-mixed bioslurry cement. This work demonstrates the potential of a seawater-mixed pozzolanic-lime mortar as an offshore road base material and a bioslurry cement as its crack repairing material.
•The optimal ratio of pozzolanic-lime mortars modified by PP fibers has been determined.•Softening coefficients of mortars are determined by soaking test.•Cracks of fly ash-lime mixture can be repaired by spraying seawater-based bioslurry cements.•The seawater-based pozzolanic-lime mortars and bioslurry cements are low-carbon emission in the production process.•The chemical component of bioslurry cements is mainly the mixture of calcium carbonate and calcite magnesian.
Nickel ions in electroplating wastewater can be removed by the bio-mineralization method. Bacillus subtilis can produce alkaline phosphatase, which hydrolyzes organophosphate monoesters and produces ...phosphate ions. Fourier-transform infrared spectroscopy (FTIR) showed that the precipitated material contains phosphate ions. X-ray diffraction (XRD) showed that nickel ions in electroplating wastewater react with Bacillus subtilis and organophosphate monoesters to obtain nickel phosphate octahydrate (Ni3(PO4)2·8H2O). The removal efficiency of nickel ions could reach 76.41% with the optimum content of the organophosphate monoester (0.02 mol), Bacillus subtilis powder (2 g), pH (6), standing time (36 h), and reaction temperature (25 °C) in the medium solution (100 mL). The average particle size of Ni3(PO4)2·8H2O was 80.51 nm, which was calculated by the Scherrer formula. The Lorentz–Transmission Electron Microscope (L-TEM) further showed that Ni3(PO4)2·8H2O was composed of clusters of irregular nanoparticles, and the individual particle size was in the range of 40–90 nm. The TGA curve shows that the mass loss of crystal water was 25.45%, which was close to the theoretical total mass loss of 28.24% in bio-Ni3(PO4)2·8H2O.
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•Nickel ions in electroplating wastewater can be removed by the Bacillus subtilis mineralization method.•The optimum removal conditions of the nickel ions were determined by the bio-mineralization experiment.•Chemical composition and microstructure of the bio-nickel phosphate were analyzed.
•The biocementation waste solution containing ammonium ions that can be converted into struvite for cementing sand columns.•Chemical components and microstructure of the resulting cementation are ...analyzed through XRD patterns and SEM images.•The cementation properties of the sand columns are determined for both bio-struvite and composite biocementation.•A comprehensive analysis of the biomineralization and biocementation mechanisms is provided.
Microbial-induced carbonate precipitation (MICP) cementation of sand results in the generation of waste liquid containing ammonium ions, posing environmental pollution concerns that necessitate appropriate treatment prior to discharge. To address this issue, the addition of hydrogen phosphate (HPO42−) and magnesium (Mg2+) salts to the biocementation waste solution (BWS) enables the efficient conversion of ammonium (NH4+) ions into environmentally friendly bio-struvite (Cell-MgNH4PO4(H2O)6, MgNH4PO4·6H2O or NH4MgPO4·6H2O) through microbial-induced struvite precipitation (MISP), thereby mitigating environmental pollution risks. X-ray diffraction (XRD) patterns confirm the presence of struvite minerals, while field emission scanning electron microscopy (FESEM) images reveal the blocky or irregular blocky structure of bio-struvite, with sizes ranging from 10 to 25 μm. The bio-struvite effectively fills the pores between sand particles, resulting in reduced permeability. Following 4 cementation levels, the permeability coefficient of the bio-struvite cemented sand column measures 5.04 × 10−3 cm/s, with a bio-struvite content of 5.12 % within the sand column. The principal chemical components of the cementitious materials in MICP and MISP composite cementation sand consist of struvite (MgNH4PO4(H2O)6, MgNH4PO4·6H2O or NH4MgPO4·6H2O) and calcium carbonate (CaCO3), forming spherical or massive aggregates smaller than 10 μm. The most effective composite cementation sands exhibit an average permeability coefficient of 4.85 × 10−4 cm/s and an unconfined compressive strength (UCS) of 197.96 kPa. Consequently, MICP and MISP composite cementation sand significantly diminishes permeability and offers a viable solution for desert dust control.
This paper proposes a green environment-friendly Bacillus subtilis to mineralize and consolidate waste incineration fly ash and heavy metal cations, and there is no harmful by-product in the ...mineralization process. Different phosphate products can be prepared, and are more stable than the microbially-induced carbonate precipitation (MICP) in nature. Typical heavy metal oxides were mainly PbO, ZnO, CdO, NiO, CuO and Cr2O3 in the chemical composition of waste incineration fly ash. Microstructure and chemical composition of waste incineration fly ash before and after treatment were characterized by powder X-ray diffraction (XRD) analysis and scanning electron microscopy. Scanning electron microscopy (SEM) images showed that the morphology of the Bacillus subtilis was mainly a rod-like structure. The optimal hydrolysis dosage of the organic phosphate monoester sodium salt was 0.2mol in the bacterial solution (1L, 20 g/L). The optimum required mass of the bacterial powder was 15 g/kg in treatment process of the waste incineration fly ash. The initial concentration of lead ions was 40.28 mg/L in waste incineration fly ash solution. After the optimum dosage treatment, the removal efficiency of lead ions was 78.15%, 79.64%, 77.70% and 80.14% when curing time was 1, 2, 4 and 6d, respectively. The waste incineration fly ash had a Shore hardness of 22 after the optimum amount of bacterial liquid treatment. Results of wind erosion test showed that the wind erosion rate of waste incineration fly ash was 2.6, 0, 0, 0, 0 and 0 g/h when blank group, deionized water, 100, 200, 300 and 400 mL of bacterial solutions treated, respectively. The bio-mineralization method provides an approach for the safe disposal of heavy metals in the contaminated areas of tailings, electroplating sewage, waste incineration plants, and so on.
•Lead ions can be removed by the bio-mineralization method.•Shore hardness of waste incineration fly ash was determined.•Optimal amount of the bacterial solution was determined.
Microbial-induced struvite precipitation (MISP) is a new biocementation method for soil improvement and hydraulic permeability reduction. Compared with traditional microbial-induced carbonate ...precipitation (MICP), MISP can significantly reduce the production of harmful ammonium ions during biochemical reactions and convert ammonium ions into struvite with promising mechanical strength. In this study, a series of experiments were conducted to compare the performance of the MICP and the MISP processes on sandy soils. Results showed that the average content of calcium carbonate in MISP cemented sand columns after 3 times of injection is similar to that in MICP cemented sand columns after 9 times of injection. The hydraulic permeability of MISP cemented sand columns after 3 times of injection is an order of magnitude lower than that of MICP cemented sand columns after 9 times of injection. To further investigate the physicochemical interactions during MISP and MICP processes, a one-dimensional finite element code considering the chemical reactions and the solute transportation was proposed. Results show that most of the MISP were formed in the early 3 h of the 6 h injection cycle, whereas most of the MICP were formed in the last 5 h of the injection cycle. The simulated total mass of the MISP precipitation, 11.3 g, was close to the experimental result of 9.6 g. The spatial distribution of MISP is more uneven as compared to MICP, as a result of the much faster reaction rate of struvite than calcium carbonate. The findings suggested that MISP could partially replace MICP in the applications of leakage mitigation and reinforcement of sandy soils.
•MISP and MICP biocementation methods are experimentally and numerically compared.•MISP method convert harmful ammonium ions into struvite with mechanical strength.•MISP method can replace MICP method in leakage mitigation and reinforcement of sandy soils.•Most of the MISP were formed in the early 3 h of the injection cycle.•Spatial distribution of precipitations of MISP is more uneven than MICP.
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