Three-dimensional (3D) chromatin architectural differences can influence the integrity of topologically associating domains (TADs) and rewire specific enhancer-promoter interactions, impacting gene expression and leading to human disease. Here, we investigate the 3D chromatin architecture in T cell acute lymphoblastic leukemia (T-ALL) using primary human leukemia specimens and its dynamic responses to pharmacological agents. Systematic integration of matched in situ Hi-C, RNA-seq and CTCF ChIP-seq datasets revealed widespread differences in intra-TAD chromatin interactions and TAD boundary insulation in T-ALL. Our studies identify and focus on a TAD “fusion” event associated with absence of CTCF-mediated insulation, enabling direct interactions between the MYC promoter and a distal super-enhancer. Moreover, our data also demonstrate that small molecule inhibitors targeting either oncogenic signal transduction or epigenetic regulation can alter specific 3D interactions found in leukemia. Overall, our study highlights the impact, complexity and dynamic nature of 3D chromatin architecture in human acute leukemia.

These results provide a new model for USP7 deubiquitinase activity through recruitment to oncogenic chromatin loci and regulation of both oncogenic transcription factors and chromatin marks to promote leukemia. Our studies also show that targeting USP7 inhibition could be a therapeutic strategy in aggressive leukemia.

Construction and improvement of industrial strains play a central role in the commercial development of microbial fermentation processes. L-tryptophan producers have usually been developed by classical random mutagenesis due to its complicated metabolic network and regulatory mechanism. However, in the present study, an L-tryptophan overproducing Escherichia coli strain was developed by defined genetic modification methodology. Feedback inhibitions of 3-deoxy-D-arabinoheptulosonate 7-phosphate synthase (AroF) and anthranilate synthase (TrpED) were eliminated by site-directed mutagenesis. Expression of deregulated AroF and TrpED was achieved by using a temperature-inducible expression plasmid pSV. Transcriptional regulation of trp repressor was removed by deleting trpR. Pathway for L-Trp degradation was removed by deleting tnaA. L-phenylalanine and L-tyrosine biosynthesis pathways that compete with L-tryptophan biosynthesis were blocked by deleting their critical genes (pheA and tyrA). The final engineered E. coli can produce 13.3 g/l of L-tryptophan. Fermentation characteristics of the engineered strains were also analyzed.

Multifunctional coatings are in urgent demand in emerging fields. In this work, nanocomposite coatings with extraordinary self-cleaning, antiwear, and anticorrosion properties were prepared on aluminum substrate by a facile spraying technique. Core-shell structured polyaniline/functionalized carbon nanotubes (PANI/fCNTs) composite and nanosized silica were synergistically integrated into ethylene tetrafluoroethylene (ETFE) matrix to construct lotus-leaf-like structures, and 1H,1H,2H,2H- perfluorooctyltriethoxysilane (POTS) was used to decrease the surface energy. The composite coating with 6 wt % PANI/fCNTs possesses superamphiphobic property, with contact angles of 167°, 163°, and 159° toward water, glycerol, and ethylene glycol, respectively. This coating demonstrates stable nonwetting performance over a wide temperature range (<400 °C), as well as outstanding self-cleaning ability to prevent contamination by sludge, concentrated H2SO4, and ethylene glycol. Superamphiphobic surface property could be maintained even after 45 000 times abrasion or bending test for 30 times. The coating displayed strong adhesive ability (grade 1 according to the GB/T9286) on the etched aluminum plate. The superamphiphobic surface could be retained after immersion in 1 mol/L HCl and 3.5 wt % NaCl solutions for 60 and 90 d, respectively. It should be noted that this coating reveals significantly improved anticorrosion performance as compared to the bare ETFE coating and ETFE composite coating without PANI/fCNTs. Such coatings with integrated functionalities offer promising self-cleaning and anticorrosion applications under erosive/abrasive environment.

Inspired by the adhesive proteins in mussels, a novel electrodeposition route has been developed to create multifunctional zinc (Zn)/ polydopamine (pDop)/ n-dodecyl mercaptan (NDM) composite coatings on different substrates, where oxidative polymerization of dopamine was simultaneously integrated during electrodeposition process. Hierarchical cauliflower-like structure was obtained on the electrodeposited Zn/pDop coatings. After modification with NDM, the prepared Zn/pDop/NDM coatings on different substrates (steel, Al and Cu) possessed excellent superhydrophobicity, exhibiting a maximum water contact angle (WCA) of 167.6° and a sliding angle (SA) less than 1° on the steel substrate.