ABSTRACT
Understanding the basis of the DNA-binding specificity of transcription factors (TFs) has been of long-standing interest. Despite extensive efforts to map millions of putative TF binding sequences, identifying the critical determinants for DNA binding specificity remains a major challenge. The coevolution of residues in proteins occurs due to a shared evolutionary history. However, it is unclear how coevolving residues in TFs contribute to DNA binding specificity. Here, we systematically collected publicly available data sets from multiple large-scale high-throughput TF-DNA interaction screening experiments for the major TF families with large numbers of TF members. These families included the Homeobox, HLH, bZIP_1, Ets, HMG_box, ZF-C4, and Zn_clus TFs. We detected TF subclass-determining sites (TSDSs) and showed that the TSDSs were more likely to coevolve with other TSDSs than with non-TSDSs, particularly for the Homeobox, HLH, Ets, bZIP_1, and HMG_box TF families. By in silico modeling, we showed that mutation of the highly coevolving residues could significantly reduce the stability of the TF-DNA complex. The distant residues from the DNA interface also contributed to TF-DNA binding activity. Overall, our study gave evidence that coevolved residues relate to transcriptional regulation and provided insights into the potential application of engineered DNA-binding domains and proteins. IMPORTANCE While unraveling DNA-binding specificity of TFs is the key to understanding the basis and molecular mechanism of gene expression regulation, identifying the critical determinants that contribute to DNA binding specificity remains a major challenge. In this study, we provided evidence showing that coevolving residues in TF domains contributed to DNA binding specificity. We demonstrated that the TSDSs were more likely to coevolve with other TSDSs than with non-TSDSs. Mutation of the coevolving residue pairs (CRPs) could significantly reduce the stability of THE TF-DNA complex, and even the distant residues from the DNA interface contribute to TF-DNA binding activity. Collectively, our study expands our knowledge of the interactions among coevolved residues in TFs, tertiary contacting, and functional importance in refined transcriptional regulation. Understanding the impact of coevolving residues in TFs will help understand the details of transcription of gene regulation and advance the application of engineered DNA-binding domains and protein.
ABSTRACT
This study investigated the corrosion susceptibility of pure titanium under uric acid exposure for 7 days based on surface analysis. The prepared pure titanium specimens, exposed to different concentrations of uric acid, were examined for surface microstructure, surface element composition and surface wettability using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and static contact angle measurement, respectively. The corrosion behaviors of titanium specimens were measured by open-circuit potential (OCP), electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization. The titanium ion release from the prepared specimens, which were immersed in Hank's balanced salt solution (HBSS) containing different amount of uric acid, was measured by inductively coupled plasma atomic emission spectrometry (ICP-AES). More irregular pitting holes were observed on titanium surfaces exposed to a high concentration of uric acid, and XPS analyses revealed that the amount of titanium dioxide (TiO2) decreased. Titanium surfaces pre-treated with high uric acid became more hydrophobic. Furthermore, the results of OCP and potentiodynamic polarization tests showed increased corrosion susceptibility of titanium samples, while EIS data indicated more active corrosion behavior of titanium materials. The high concentration of uric acid also induced titanium ion release. High concentration of uric acid negatively influenced the surface characteristics and corrosion properties of titanium materials, which destroyed the titanium oxide film barrier. High uric acid exposure increased corrosion susceptibility of pure titanium specimens and accelerated titanium ion release. Graphical abstract.
Subject(s)
Titanium , Uric Acid , Corrosion , Materials Testing , Photoelectron Spectroscopy , Surface Properties , Titanium/chemistryABSTRACT
In this study, we established a procedure to prepare a Semaphorin4D (SEMA4D)-immobilized titanium surface and explored its effects on macrophage behaviors in an endothelial cell/macrophage indirect coculture model. The SEMA4D-bovine serum albumin complex was immobilized onto a preprocessed poly L-lysine titanium surface through NaOH hydrothermal treatment and self-assembly technology. All titanium specimens were examined for surface microstructure, surface element composition, and surface wettability by field emission scanning electron microscopy, x-ray photoelectron spectroscopy (XPS), and water contact angle measurement, respectively. Subsequently, we constructed an endothelial cell/macrophage indirect coculture model and evaluated the activation of NF-κB signaling pathway and the expression of proinflammatory cytokines (TNFα, IL-6, and IL-1ß) in macrophages. In XPS analysis, the SEMA4D-immobilized titanium surface appeared as a loose porous structure covered with uniform film, which exhibited better hydrophilicity than the control smooth titanium surface. In the indirect coculture model, SEMA4D attenuated the activation of NF-κB signaling pathway of lipopolysaccharide-stimulated THP-1 macrophages, thereby downregulating the expression of proinflammatory cytokines in macrophages. In conclusion, SEMA4D could be immobilized on titanium surfaces through NaOH hydrothermal treatment and self-assembly technology. Meanwhile, SEMA4D immobilization altered the characteristics of the titanium surfaces, which negatively regulated macrophage behaviors in the endothelial cell/macrophage indirect coculture model.
Subject(s)
Macrophages , Titanium , Anti-Inflammatory Agents/pharmacology , Antigens, CD , Coculture Techniques , Endothelial Cells , Macrophages/metabolism , Semaphorins , Surface Properties , Titanium/chemistryABSTRACT
The presence of metal ions, such as titanium (Ti) ions, is toxic to adjacent tissues of implants. Indeed, Ti ions may induce an inflammatory response through the NF-κB pathway, thus causing damage to soft and hard tissues. The involvement of Yes-associated protein (YAP), a key factor of the Hippo pathway, in an immuno-inflammatory response has been confirmed, whereas its role in Ti ion-mediated inflammation has not been elucidated. Therefore, this study aimed to investigate the role of signal crosstalk between the Hippo/YAP and NF-κB signaling pathways in the pro-inflammatory effect of Ti ions on macrophages. In our work, RAW264.7 cells were cocultured with Ti ions. The migration capacity of macrophages under Ti ion exposure was measured by transwell assay. Western blot analysis was used to detect the expressions of related proteins. Polymerase chain reaction was used to evaluate the expression of pro-inflammatory cytokines. The nucleus translocation of YAP and P65 was visualized and analyzed via immunofluorescence staining. The results showed that the migration of macrophages was promoted under Ti ion exposure. Ten parts per million Ti ions induced nuclear expression of YAP and activated the NF-κB pathway, which finally upregulated the expression of pro-inflammatory cytokines in macrophages. Moreover, the inhibition of the NF-κB pathway rescued the reduction of YAP expression under Ti ion exposure. Most importantly, the overexpression of YAP exacerbated the inflammatory response mediated by Ti ions through the NF-κB pathway. In summary, this study explored the mechanism of Hippo-YAP/NF-κB pathway crosstalk involved in the regulation of macrophage behaviors under Ti ion exposure.
Subject(s)
Hippo Signaling Pathway/drug effects , Hippo Signaling Pathway/genetics , Inflammation Mediators/metabolism , Inflammation/etiology , Inflammation/genetics , Macrophages/drug effects , Titanium/toxicity , Animals , Cell Proliferation/drug effects , Mice , Phosphorylation/drug effects , Signal Transduction/drug effectsABSTRACT
To improve lithium storage performances of Si anode for lithium-ion batteries, Si nanoparticles encapsulated into porous N-doped carbon (Si@PNC) was devised and prepared by metal nitrate accelerated polymer blowing process. The Si@PNC composites have large specific surface area of 221.7 m² g-1 and possess a great deal of mesopores and micropores, which are attributed to the carbonization of PVP and etching metallic nanoparticles. As anode for lithium ion battery, the initial discharge capacity of Si@PNC composites is high to 1626 mA h g-1, and the specific capacity still retains 1030 mA h g-1 after 200 cycles at 200 mA g-1. Meanwhile, remarkably improved rate capability is achieved with an excellent reversible specific capacity of 375 mA h g-1 at 5.0 A g-1. The excellent lithium storage performances benefit from the unique porous core-shell structure of Si@PNC composites, which improve electroconductivity, reduce volume dilatation and accelerate lithium ion transmission.
ABSTRACT
Titanium (Ti) and its alloys as bio-implants have excellent biocompatibilities and osteogenic properties after modification of chemical composition and topography via various methods. The corrosion resistance of these modified materials is of great importance for changing oral system, while few researches have reported this point. Recently, oxidative corrosion induced by cellular metabolites has been well concerned. In this study, we explored the corrosion behaviors of four common materials (commercially pure Ti, cp-Ti; Sandblasting and acid etching-modified Ti, Ti-SLA; nanowires-modified Ti, Ti-NW; and zinc-containing nanowires-modified Ti, Ti-NW-Zn) with excellent biocompatibilities and osteogenic capacities under the macrophages induced-oxidizing microenvironment. The results showed that the materials immersed into a high oxidizing environment were more vulnerable to corrode. Meanwhile, different surfaces also showed various corrosion susceptibilities under oxidizing condition. Samples embed with zinc element exhibited more excellent corrosion resistance compared with other three surfaces exposure to excessive H2O2. Besides, we found that zinc-decorated Ti surfaces inhibited the adhesion and proliferation of macrophages on its surface and induced the M2 states of macrophages to better healing and tissue reconstruction. Most importantly, zinc-decorated Ti surfaces markedly increased the expressions of antioxidant enzyme relative genes in macrophages. It improved the oxidation microenvironment around the materials and further protected their properties. In summary, our results demonstrated that Ti-NW-Zn surfaces not only provided excellent corrosion resistance properties, but also inhibited the adhesion of macrophages. These aspects were necessary for maintaining osseointegration capacity and enhancing the corrosion resistance of Ti in numerous medical applications, particularly in dentistry.
Subject(s)
Hydrogen Peroxide/chemistry , Nanowires/chemistry , Titanium/chemistry , Zinc/chemistry , Animals , Biocompatible Materials , Cell Adhesion , Cell Line , Cell Proliferation , Corrosion , Dental Implants , Macrophages/metabolism , Mice , Oxidation-Reduction , Surface PropertiesABSTRACT
To tackle the issue of poor cycling stability for metal oxide nanoparticles as supercapacitor electrode, porous ZnO/Co3O4 composites were fabricated via solid-state thermolysis of [CoZn(BTC)(NO3)](2H2O)(0.5DMF) under air atmosphere. The results demonstrate that the products are mesoporous polyhedron structure with the diameter of about 10 µm, which are constructed by many interconnected nanocrystals with the sizes of around 20 nm. ZnO/Co3O4 composites as supercapacitor electrode exhibited excellent cyclic stability capacity, showing a maximum specific capacitance of 106.7 F g-1 and a capacity retention of 102.7 F · g-1 after 1000 cycles at 0.5 A · g-1. The superior electrochemical performance was contributed to ZnO/Co3O4 composites with porous structures and small size, which shortened the route of electronic transmission as well as ions insertion and desertion processes. Additionally, the synergetic effect of bimetallic oxides improved the electrochemical stability.