DiffDomain enables identification of structurally reorganized topologically associating domains.

Topologically associating domains (TADs) are critical structural units in three-dimensional genome organization of mammalian genome. Dynamic reorganizations of TADs between health and disease states are associated with essential genome functions. However, computational methods for identifying reorganized TADs are still in the early stages of development. Here, we present DiffDomain, an algorithm leveraging high-dimensional random matrix theory to identify structurally reorganized TADs using high-throughput chromosome conformation capture (Hi-C) contact maps. Method comparison using multiple real Hi-C datasets reveals that DiffDomain outperforms alternative methods for false positive rates, true positive rates, and identifying a new subtype of reorganized TADs. Applying DiffDomain to Hi-C data from different cell types and disease states demonstrates its biological relevance. Identified reorganized TADs are associated with structural variations and epigenomic changes such as changes in CTCF binding sites. By applying to a single-cell Hi-C data from mouse neuronal development, DiffDomain can identify reorganized TADs between cell types with reasonable reproducibility using pseudo-bulk Hi-C data from as few as 100 cells per condition. Moreover, DiffDomain reveals differential cell-to-population variability and heterogeneous cell-to-cell variability in TADs. Therefore, DiffDomain is a statistically sound method for better comparative analysis of TADs using both Hi-C and single-cell Hi-C data.

Oxidative degradation of UV-irradiated polyethylene by laccase-mediator system.

Polyethylene (PE) is one of the most widely used plastics. However, the chemical inertness, inefficient recycling, and random landfilling of PE waste have caused serious pollution to the natural environment. In this study, a series of laccase-mediator systems (LMS) were constructed by combination of two laccases from Botrytis aclada (BaLac) and Bacillus subtilis (BsLac) with three synthetic mediators (ABTS, HBT, and TEMPO) to oxidize LDPE films (UVPE) pretreated with high-temperature UV irradiation. Scanning electron microscopy showed aging phenomena such as etching, fragmentation, and cracking on the surface of the UVPE films after LMS incubation. The FTIR results showed that LMS-UVPE added new oxygen-containing functional groups such as -OH, -CO, and CC. High-temperature gel chromatography confirmed that the average reduction in weight-average molecular weight (Mw) was approximately 40% for the BaLac experimental group. GC-MS analysis showed the presence of oxygen-containing products, such as aldehydes, ketones, and alcohols, in the reaction mixture. To verify the oxidation process UVPE degradation by LMS, we inferred three possible pathways by combined analysis of the oxidation products of LMS on UVPE and model substrates oleic acid and squalene.

Oxidative degradation of pre-oxidated polystyrene plastics by dye decolorizing peroxidases from Thermomonospora curvata and Nostocaceae.

Biodegradation of PS has attracted lots of public attentions due to its environmental friendliness. However, no specific PS degrading enzyme has been identified yet. Dye decolorizing peroxidases (DyPs) are heme-containing peroxidases named for the ability to degrade a variety of organic dyes. Herein, the abilities of two DyPs from Thermomonospora curvata (TcDyP) and Nostocaceae (AnaPX) to degrade PS were evaluated. Preoxidation methods by ultraviolet (UV) irradiation and chemical oxidants were developed to initially activate C-C bonds in the PS skeleton. DyPs degradation caused obvious etching and enhanced hydrophilicity of UV-PS films, and also generated new CO and C-OH groups. The cleavage of activated C-C bonds by DyPs was experimentally proven by analyzing the degradation products of UV-PS and model substrates. Furthermore, better pre-oxidation was obtained by using chemical oxidants KMnO4/H2SO4 and mCPBA to oxidize PS materials in dissolved state. And AnaPX exhibited stronger degradation effects on KMnO4/H2SO4-PS and mCPBA-PS by causing greater changes in functional groups CO, C-O, -OH groups and substituted benzenes and higher molecular weight reductions of 19.7% and 31.0%, respectively. To our knowledge, this is the first report on the identification of PS-degrading enzymes that provides experimental evidence.

Accelerated biodegradation of polyethylene terephthalate by Thermobifida fusca cutinase mediated by Stenotrophomonas pavanii.

Polyethylene terephthalate (PET) is a general plastic that produces a significant amount of waste due to its non-biodagradable properties. We obtained four bacteria (Stenotrophomonas pavanii JWG-G1, Comamonas thiooxydans CG-1, Comamonas koreensis CG-2 and Fulvimonas soli GM-1) that utilize PET as a sole carbon source through a novel stepwise screening and verification strategy. PET films pretreated with S. pavanii JWG-G1 exhibited weight loss of 91.4% following subsequent degradation by Thermobifida fusca cutinase (TfC). S. pavanii JWG-G1 was able to colonize the PET surface and maintain high cell viability (over 50%) in biofilm, accelerating PET degradation. Compared with PET films with no pretreatment, pretreatment with S. pavanii JWG-G1 caused the PET surface to be significantly rougher with greater hydrophilicity (contact angle of 86.3 ± 2° vs. 96.6 ± 2°), providing better opportunities for TfC to contact and act on PET. Our study indicates that S. pavanii JWG-G1 could be used as a novel pretreatment for efficiently accelerating PET biodegradation by TfC.

Leonurine Regulates Treg/Th17 Balance to Attenuate Rheumatoid Arthritis Through Inhibition of TAZ Expression.

Leonurine, an active alkaloid extracted from Herba leonuri, is reported to have potent anti-inflammatory activity against rheumatoid arthritis (RA). However, the molecular mechanism of action of leonurine in RA remains poorly understood. In this study, we detected 3,425 mRNAs differentially expressed between CD4+ T cells of RA patients and those of healthy individuals using microarray raw data mining. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes including T-helper (Th)-17 cell development, and was thus selected for functional verification. In a naïve CD4+ T cell differentiation assay, we found that TAZ overexpression was associated with impaired balance between T regulatory (Treg) and Th17 cells in vitro. TAZ overexpression increased the levels of the pro-inflammatory cytokines interleukin (IL)-17, IL-1ß, and tumor necrosis factor (TNF)-α and decreased that of the anti-inflammatory cytokine IL-10. Leonurine treatment had a direct recovery effect on the impaired balance and reduced the expression of TAZ and led to normalization of IL-17, IL-1ß, and TNF-α and IL-10. Furthermore, IL-6 was found to promote the expression of TAZ and receptor activator of nuclear factor kappa-B ligand (RANKL), and RANK. Leonurine significantly inhibited TAZ-mediated expression of RANKL, and RANK and IL-6 in synovial fibroblasts. We conclude that the therapeutic effect of leonurine was through suppression of TAZ led to restoration of Treg/Th17 balance and suppression of synovial fibroblast action.

Iterative learning-based decentralized adaptive tracker for large-scale systems: a digital redesign approach.

In this paper, a digital redesign methodology of the iterative learning-based decentralized adaptive tracker is proposed to improve the dynamic performance of sampled-data linear large-scale control systems consisting of N interconnected multi-input multi-output subsystems, so that the system output will follow any trajectory which may not be presented by the analytic reference model initially. To overcome the interference of each sub-system and simplify the controller design, the proposed model reference decentralized adaptive control scheme constructs a decoupled well-designed reference model first. Then, according to the well-designed model, this paper develops a digital decentralized adaptive tracker based on the optimal analog control and prediction-based digital redesign technique for the sampled-data large-scale coupling system. In order to enhance the tracking performance of the digital tracker at specified sampling instants, we apply the iterative learning control (ILC) to train the control input via continual learning. As a result, the proposed iterative learning-based decentralized adaptive tracker not only has robust closed-loop decoupled property but also possesses good tracking performance at both transient and steady state. Besides, evolutionary programming is applied to search for a good learning gain to speed up the learning process of ILC.