TFTG: A comprehensive database for human transcription factors and their targets.

Transcription factors (TFs) are major contributors to gene transcription, especially in controlling cell-specific gene expression and disease occurrence and development. Uncovering the relationship between TFs and their target genes is critical to understanding the mechanism of action of TFs. With the development of high-throughput sequencing techniques, a large amount of TF-related data has accumulated, which can be used to identify their target genes. In this study, we developed TFTG (Transcription Factor and Target Genes) database (http://tf.liclab.net/TFTG), which aimed to provide a large number of available human TF-target gene resources by multiple strategies, besides performing a comprehensive functional and epigenetic annotations and regulatory analyses of TFs. We identified extensive available TF-target genes by collecting and processing TF-associated ChIP-seq datasets, perturbation RNA-seq datasets and motifs. We also obtained experimentally confirmed relationships between TF and target genes from available resources. Overall, the target genes of TFs were obtained through integrating the relevant data of various TFs as well as fourteen identification strategies. Meanwhile, TFTG was embedded with user-friendly search, analysis, browsing, downloading and visualization functions. TFTG is designed to be a convenient resource for exploring human TF-target gene regulations, which will be useful for most users in the TF and gene expression regulation research.

The landscape of immune checkpoint-related long non-coding RNAs core regulatory circuitry reveals implications for immunoregulation and immunotherapy responses.

Long non-coding RNAs (lncRNAs) could modulate expression of immune checkpoints (ICPs) by cooperating with immunity genes in tumor immunization. However, precise functions in immunity and potential for predicting ICP inhibitors (ICI) response have been described for only a few lncRNAs. Here we present an integrated framework that leverages network-based analyses and Bayesian network inference to identify the regulated relationships including lncRNA, ICP and immunity genes as ICP-related LncRNAs mediated Core Regulatory Circuitry Triplets (ICP-LncCRCTs) that can make robust predictions. Hub ICP-related lncRNAs such as MIR155HG and ADAMTS9-AS2 were highlighted to play central roles in immune regulation. Specific ICP-related lncRNAs could distinguish cancer subtypes. Moreover, the ICP-related lncRNAs are likely to significantly correlated with immune cell infiltration, MHC, CYT. Some ICP-LncCRCTs such as CXCL10-MIR155HG-ICOS could better predict one-, three- and five-year prognosis compared to single molecule in melanoma. We also validated that some ICP-LncCRCTs could effectively predict ICI-response using three kinds of machine learning algorithms follow five independent datasets. Specially, combining ICP-LncCRCTs with the tumor mutation burden (TMB) improves the prediction of ICI-treated melanoma patients. Altogether, this study will improve our grasp of lncRNA functions and accelerating discovery of lncRNA-based biomarkers in ICI treatment.

Identifying immune checkpoint-related lncRNA biomarkers for immunotherapy response and prognosis in cancers.

Long non-coding RNAs (lncRNAs) could modulate expression of immune checkpoints (ICPs) in tumor-immune. However, precise functions in immunity and potential for predicting ICP inhibitors (ICI) response have been described for only a few lncRNAs. Here, a multiple-step pipeline was developed to identify cancer- and immune-context ICP and lncRNA cooperative regulation pairs (ICPaLncCRPs) across cancers. Immune-related ICPs and lncRNAs were extracted follow immune cell lines and immunologic constant of rejection groups. ICPaLncCRP networks were constructed, which likely to modulate tumor-immune by specific patterns. Common and specific hub ICPaLncs such as MIR155HG, TRG-AS1 and PCED1B-AS1 maybe play central roles in prognosis and circulating. Moreover, these hub ICPaLncs were significantly correlated with immune cell infiltration based on bulk and single-cell RNA sequencing data. Some ICPaLncCRPs such as IDO1-MIR155HG could predict three- and five-year prognosis of melanoma in two independent datasets. We also validated that some ICPaLncCRPs could effectively predict ICI-response follow six independent datasets. Collectively, this study will enhance our understanding of lncRNA functions and accelerate discovery of lncRNA-based biomarkers in ICI treatment.

Reduction-Responsive Supramolecular Sheets for Selective Regulation of Facultative Anaerobe Agglutination.

Stimuli-responsive supramolecular materials have promising biological applications because of their ability to rapidly undergo significant structural changes in response to diverse stimuli. Herein, supramolecular sheets assembled via charge-transfer interactions between the pyrene moiety of a d-mannose-containing amphiphile and 7,7,8,8-tetracyanoquinodimethane (TCNQ) are reported. The supramolecular sheets show reduction-responsive behavior, in which their disassembly is triggered by the reduction of TCNQ by sodium sulfide. In an anaerobic environment, the sheet structure remains intact and the exposed d-mannose moieties induce the agglutination of facultative anaerobes, thereby inhibiting bacterial growth. In contrast, in an aerobic environment, the reduction of TCNQ by the hydrogen sulfide generated by facultative anaerobes causes sheet disassembly. This enables continuous bacterial growth, because the collapsed sheets cannot induce agglutination. Thus, this study presents a novel supramolecular material for the selective regulation of facultative anaerobe growth according to the external environment.

Superior Thermal Conductivity of Graphene Film/Cu-Zr Alloy Composites for Thermal Management Applications.

As the power density of electronic devices continuously increases, there is a growing demand to improve the heat conduction performance of thermal management materials for addressing heat dissipation issues. Single-/few-layer graphene is a promising candidate as a filler of a metal matrix due to its extremely high thermal conductivity (k); however, the well-arranged assembly of 2D-component graphene with a high volume fraction remains challenging. Herein, we integrated a novel graphene-based macroscopic material of graphene film (GF) into a Cu matrix by infiltrating molten Zr-microalloyed Cu into a spirally folded and upright-standing GFs skeleton. The microstructure of the GF/Cu composites was regulated by an interface modification strategy. The GF/Cu composites with a spirally layered microstructure exhibit a superior k of 820 W/m K in the axial direction, much higher than that of Cu-matrix composites reinforced with graphene nanosheets (generally <500 W/m K) and twice that of Cu. The thermal transfer mechanisms were investigated by experiments and theoretical calculations. The results reveal that the excellent performance is attributed to the construction of high-heat conduction channels and a positive coordinating effect at the Zr-modified GF/Cu interface. Meanwhile, the relation between interfacial microstructure and heat transfer is established in the composites using interfacial thermal resistance as a bridge. This work yields in-depth insight into the heat conduction mechanism in highly oriented structures and provides a promising solution for the thermal management issues of high-power electronics.

Reduced Graphene Oxide Nanosheets Decorated with Copper and Silver Nanoparticles for Achieving Superior Strength and Ductility in Titanium Composites.

Graphene and its derivates are extensively applied to enhance the mechanical properties of metal matrix nanocomposites. However, their high reactivity with a metal matrix such as titanium and thus the limited strengthening effects are major problems for achieving high-performance graphene-based nanocomposites. Herein, reduced graphene oxide nanosheets decorated with copper or silver (i.e., Cu@rGO and Ag@rGO) nanopowders are introduced into Ti matrix composites using multiple processes of one-step chemical coreduction, hydrothermal synthesis, low-energy ball milling, spark plasma sintering, and hot rolling. The Cu@rGO/Ti and Ag@rGO/Ti nanocomposites exhibit significantly enhanced strength with superior elongation to fracture (846 MPa-11.6 and 900 MPa-8.4%, respectively, basically reaching the level of the commercial Ti-6Al-4V titanium alloy), which are much higher than those of the fabricated Ti (670 MPa-7.0%) and rGO/Ti composites (726 MPa-11.3%). Furthermore, fracture toughness values of the M@rGO/Ti composites are all significantly improved, that is, the highest KIC value is 34.4 MPa·m1/2 for 0.5Cu@rGO/Ti composites, which is 20.28 and 51.5% higher than those of monolithic Ti and 0.5rGO/Ti composites, respectively. The outstanding mechanical properties of Ag@rGO/Ti and Cu@rGO/Ti composites are attributed to the effective load transfer of in situ formed TiC nanoparticles and the formation of interfacial intermetallic compounds between the rGO nanosheets and Ti matrix. This study provides new insights and approach for the fabrication of metal-modified graphene/Ti composites with a high performance.

Supramolecular Tubule from Seesaw Shaped Amphiphile and Its Hierarchical Evolution into Sheet.

Although supramolecular one-dimensional (1D) and two-dimensional (2D) structures with various unique properties have been extensively studied, the reversible switching between tubules and sheets via lateral association remains challenging. Here, we report the unique structures of a supramolecular tubular bamboo culm in which the hollow-tubular interior is separated, at intervals, by nodes per 1.3 nm. Interestingly, the discrete tubules are able to hierarchically assemble into a flat sheet in response to an aromatic guest. The addition of trans-azobenzene, as a guest, enables the tubules to form a hierarchical sheet assembly via the lateral interaction. The hierarchical sheet structures are disassembled into their constituent tubules upon UV irradiation due to trans-cis isomerization. The recovery from cis-azobenzene to trans-form induces repeatedly the hierarchical sheet assembly, indicative of a reversible switching behavior between tubules and sheets triggered by an external stimulus.

Formation Mechanism and Cohesive Energy Analysis of Metal-Coated Graphene Nanocomposites Using In-Situ Co-Reduction Method.

Nanocomposite powders based on metal-coated graphene were synthesized using an in-situ co-reduction method in order to improve wettability and interfacial bonding between graphene and metal. Graphene oxide (GO) of 2~3 atomic layers was synthesized using the Hummer's method with graphite as a raw material and then dispersed into a dispersing agent solution mixed with N-Methyl pyrrolidone and deionized water to form a homogeneous GO suspension, which was finally added into electroless plating solutions for the reduction process. Copper-coated graphene (Cu@graphene) and nickel-coated graphene (Ni@graphene) were synthesized using this one-step and co-reduction method by mixing salt solutions containing metal ions and GOs into the plating solution. The Cu ions or Ni ions were adsorbed and bonded onto the edges and surfaces of graphene, which was reduced from the GOs using a strong reducing agent of ascorbic acid or sodium borohydride. Crystalline Cu particles with an average size of about 200 nm were formed on the surface of graphene, whereas amorphous or nanocrystalline Ni particles with an average size of 55 nm were formed on the surface of graphene. Distribution of these metal particles on the graphene is homogeneous and highly dispersed, which can effectively improve the sinterability of composite powders. Cohesive energy distribution between graphene and metal interface was analyzed using first-principle calculation method. Formation mechanism of metal coated graphene was identified to be that both the GO and metal ions were simultaneously reduced in the reducing agents and thus a chemical bonding of graphene/metal was formed between the metal particles and graphene.

Synergistic enhancing effect for mechanical and electrical properties of tungsten copper composites using spark plasma infiltrating sintering of copper-coated graphene.

Successful applications of WCu alloys in high voltage electrical switches require their high strength and excellent conductivity. Unfortunately, the strategies for increasing their strength such as doping with fine particles and alloying often significantly decrease their conductivity. In this paper, we developed a new pathway for fabricating WCu alloys using spark plasma infiltrating sintering of copper-coated graphene (Cu@Gr) composite powders. Cu@Gr was found to partially prevent the formation of WC after sintering, and graphene was uniformly distributed on the surfaces of network Cu phases. Electrical conductivity of 38.512 M·S/m, thermal conductivity of 264 W·m-1·K-1 and microhardness of 278 HV were achieved for the sintered WCu composites doped with only 0.8 wt.% Cu@Gr powders, which showed 95.3%, 24.3%, 28% enhancement compared with those from the conventional sintering using the undoped WCu powders.