PTK2B promotes TBK1 and STING oligomerization and enhances the STING-TBK1 signaling.

TANK-binding kinase 1 (TBK1) is a key kinase in regulating antiviral innate immune responses. While the oligomerization of TBK1 is critical for its full activation, the molecular mechanism of how TBK1 forms oligomers remains unclear. Here, we show that protein tyrosine kinase 2 beta (PTK2B) acts as a TBK1-interacting protein and regulates TBK1 oligomerization. Functional assays reveal that PTK2B depletion reduces antiviral signaling in mouse embryonic fibroblasts, macrophages and dendritic cells, and genetic experiments show that Ptk2b-deficient mice are more susceptible to viral infection than control mice. Mechanistically, we demonstrate that PTK2B directly phosphorylates residue Tyr591 of TBK1, which increases TBK1 oligomerization and activation. In addition, we find that PTK2B also interacts with the stimulator of interferon genes (STING) and can promote its oligomerization in a kinase-independent manner. Collectively, PTK2B enhances the oligomerization of TBK1 and STING via different mechanisms, subsequently regulating STING-TBK1 activation to ensure efficient antiviral innate immune responses.

Multispectral higher-order Fano resonant metasurface based on periodic twisted DNA-like split ring arrays with three modulation methods.

The active modulation of the Fano resonance is rare but desirable. However, recent studies mostly focused on a single modulation method and few reported the use of three photoelectric control methods. A tunable graphene DNA-like metamaterial modulator with multispectral Fano resonance is demonstrated. In experimentally fabricated metamaterials with six photoelectric joint modulation patterns, each joint shows different optoelectrical response characteristics. Ultrahigh modulation depth (MD) up to 982% was achieved at 1.5734 THz with a 1.040 A external laser pump by involving combined optoelectrical methods. These results show that the metasurface modulator is a promising platform for higher-order Fano resonance modulation and communication fields.

Dual control of multi-band resonances with a metal-halide perovskite-integrated terahertz metasurface.

The phenomenon of multi-resonant Fano resonances is important for the design of biosensors and communication fields. There are very few studies reporting the multi-band Fano resonance metamaterials with more than three resonance frequencies, or the tunable optical metamaterials to control the multi-band Fano resonance characteristics. Here, we report dual control of multi-band Fano resonances with a metal-halide perovskite-integrated terahertz metasurface by lasers and an electrical field. By tuning the conductivity of the perovskite film on the metasurface, ultrasensitive optoelectronic modulation was achieved. The terahertz transmission amplitude exhibited increasing and decreasing stages. We analyzed the physical phenomena and found that capacitance effects and Fermi-level enhancement had significant roles in the optical- and electronic-modulation experiments. The resonant frequencies in the electronic modulation had broader frequency shifts and a higher and wider tunable modulation depth range. More importantly, the maximum modulation depth was as high as 197%, with a significant fluctuation in the amplitude and more unstable frequency shifts in the transmission spectra.

Time-frequency joint mappings of a terahertz metasurface for multi-dimensional analysis of biological cells.

Traditional fast Fourier transform is used to extract the frequency component at the cost of losing the time domain, which is critical for metasurface biosensing. In this Letter, a more comprehensive algorithm, continuous wavelet transform (CWT), to process signals from THz time-domain spectroscopy is introduced. By comparing the metasurface-enhanced 2D time-frequency mappings (TFMs) of HaCaT and HSC3 cells, the two types of biological cells can be clearly differentiated, showing the great potential of CWT in the label-free recognition of biological cells. Also, the 2D TFMs serve as effective visualization indicators, successfully detecting the concentration of cancer cells characterized by being label free and low cost. In addition, the 2D TFMs of different metasurfaces under the same cell concentration reveal the correlation of TFMs and localized fields. Such a feature provides evidence of an interaction between biological cells and electromagnetic waves, implying the absorption of THz radiation by biological cells can be effectively controlled by properly designing split ring resonators (SRRs) of metasurfaces.

KIZ/GM114 Balances the NF-ĸB Signaling by Antagonizing the Association of TRAF2/6 With Their Upstream Adaptors.

NF-κB signaling is a pivotal regulator of the inflammatory response and it must be tightly controlled to avoid an excessive inflammatory response that may lead to human chronic inflammatory and autoimmune diseases. Thus, how NF-κB signaling is precisely controlled is a long-standing question in the field. TRAF family proteins function as key adaptors to mediate NF-κB signaling induced by various receptors. Here, we characterize KIZ/GM114 as a negative regulator balancing the NF-κB signaling. Mechanistically, KIZ/GM114 binds TRAF6/2 by targeting the TRAF domains to antagonize the TRAF6-IRAK1 association or the TRAF2-TRADD association, consequently reducing the IL-1ß/LPS/TNFα-induced NF-κB activation. Importantly, upon dextran sulfate sodium treatment, Gm114 deficiency induces a stronger inflammatory response, more severe acute colitis and lower survival rate in mice compared with control mice. Collectively, our study not only identifies KIZ/GM114 as a negative regulator to balance the NF-κB signaling, but it also implies a new strategy for limiting excessive inflammatory response.

Adhesive, Antibacterial, Conductive, Anti-UV, Self-Healing, and Tough Collagen-Based Hydrogels from a Pyrogallol-Ag Self-Catalysis System.

Recently, versatile hydrogels with multifunctionality have been widely developed with emerging applications as wearable and implantable devices. In this work, we reported novel versatile hydrogels by self-catalyzing the gelation of an interpenetrating polymer network consisting of acrylic acid (AA) monomers and GA-modified collagen (GCOL) in situ decorated silver nanoparticles (AgNPs). The resultant hydrogel, namely AgNP@GCOL/PAA, has many desirable features, including good mechanical properties (such as 123 kPa, 916%, and 1961 J m-2 for the fracture stress, strain and tearing energy) that match with those of animal skin, excellent self-healing performance, favorable conductivity and strain sensitivity as a flexible biosensor, and excellent antibacterial and anti-UV properties, as well as the strong adhesiveness on skin. Moreover, AgNP@GCOL/PAA showed excellent biocompatibility via in vitro cell culture. Remarkably, AgNP@GCOL/PAA displayed superior hemostatic properties with sharply decreasing blood loss for a mouse liver incision, closely related to its strong self-adhesion which produced anchoring strength to the bleeding site and thus formed a network barrier with liver tissue. This study provides new opportunities for the facile preparation of widely used multifunctional collagen-based hydrogels based on a simple pyrogallol-Ag system.

Corrigendum: ZDHHC11 Positively Regulates NF-κB Activation by Enhancing TRAF6 Oligomerization.

[This corrects the article DOI: 10.3389/fcell.2021.710967.].

ZDHHC11 Positively Regulates NF-κB Activation by Enhancing TRAF6 Oligomerization.

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a RING domain ubiquitin ligase that plays an important role in nuclear factor-κB (NF-κB) signaling by regulating activation of the TAK1 and IKK complexes. However, the molecular mechanisms that regulate TRAF6 E3 activity remain unclear. Here, we found that ZDHHC11, a member of the DHHC palmitoyl transferase family, functions as a positive modulator in NF-κB signaling. ZDHHC11 overexpression activated NF-κB, whereas ZDHHC11 deficiency impaired NF-κB activity stimulated by IL-1ß, LPS, and DNA virus infection. Furthermore, Zdhhc11 knockout mice had a lower level of serum IL6 upon treatment with LPS and D-galactosamine or HSV-1 infection than control mice. Mechanistically, ZDHHC11 interacted with TRAF6 and then enhanced TRAF6 oligomerization, which increased E3 activity of TRAF6 for synthesis of K63-linked ubiquitination chains. Collectively, our study indicates that ZDHHC11 positively regulates NF-κB signaling by promoting TRAF6 oligomerization and ligase activity, subsequently activating TAK1 and IKK complexes.

Novel Modification of Collagen: Realizing Desired Water Solubility and Thermostability in a Conflict-Free Way.

Because of poor water solubility and low thermostability, the application of collagen is limited seriously in fields such as injectable biomaterials and cosmetics. In order to overcome the two drawbacks simultaneously, a novel bifunctional modifier based on the esterification of polyacrylic acid (PAA) with N-hydroxysuccinimide (NHS) was prepared. The esterification degree of PAA-NHS esters was increased upon increasing the NHS dose, which was confirmed by Fourier-transform infrared (FTIR) and nuclear magnetic resonance spectrascopy. FTIR results indicated that the triple helix of the modified collagens remained integrated, whereas the molecular weight became larger, as reflected by the sodium dodecyl sulfate-polyacrylamide gel electrophoresis pattern. The modified collagens displayed excellent water solubility under neutral condition, owing to lower isoelectric point (3.1-4.3) than that of native collagen (7.1). Meanwhile, denaturation temperatures of the modified collagens were increased by 4.8-5.9 °C after modification. The modified collagen displayed hierarchical microstructures, as reflected by field-emission scanning electron microscopy, while atomic force microscopy further revealed a "fishing net-like" network in the nanoscale, reflecting a unique aggregation behavior of collagen macromolecules after modification. As a whole, the PAA-NHS ester as a bifunctional modifier endowed collagen with desired water solubility and thermostability in a conflict-free manner, which was beneficial to the process and application of the water-soluble collagen.

Dual-functionalized hyaluronic acid as a facile modifier to prepare polyanionic collagen.

Hyaluronic acid (HA) is a natural polysaccharide possesses outstanding physiological activities. In this work, HA was activated as a novel collagen modifier via the esterification reaction between N-hydroxysuccinimide (NHS) and the carboxyl groups of HA. Both of Fourier transform infrared spectroscopy (FTIR) and 1H- nuclear magnetic resonance (NMR) spectra indicated the successful synthesis of HA-NHS esters. As reflected by FTIR, circular dichroism (CD) and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), collagens modified with HA-NHS ester maintained its intact triplex structure with larger molecular weight. The resultant polyanionic collagen displayed an excellent dissolubility in the neutral water to form a clear solution, due to the significantly lower isoelectric point values (3.8-4.4) compared with that of the native collagen (7.1). In addition, the thermal transition temperature of collagen was significantly increased (16 °C) after modifying with HA-NHS esters. Both of the aggregation morphology and rheological property exhibited high dependence on the NHS/COOH ratio of HA-NHS esters, as reflected by field-emission scanning electron microscopy (FESEM) and rheological test, respectively. The present study offered a novel dual-functional modifier based on the design of HA-NHS ester to obtain water-soluble collagen with desired thermal stability and rheological property, which will significantly widen the application range of collagen, especially in the fields of injectable biodegradable materials and cosmetics.

Temperature and pH responsive cellulose filament/poly (NIPAM-co-AAc) hybrids as novel adsorbent towards Pb(II) removal.

A novel thermo- and pH sensitive adsorbent, composed of cellulose filament (CF) as the reinforcement scaffold and crosslinked copolymer of, N-isopropylacrylamide (NIPAM) as the thermosensitive component and acrylic acid (AAc) as the pH sensitive component was prepared. SEM images indicated the formation of semi-interpenetrating network between CF and poly(NIPAM-co-AAc). FTIR spectra displayed the characteristic peaks for CF and poly(NIPAM-co-AAc). DSC reflected the lower critical solution temperature derived from PNIPAM in the hybrids. The swelling ratios exhibited dependence on temperature and pH. The adsorption of Pb(II) on CF/poly(NIPAM-co-AAc) reflected pH-dependence. The adsorption kinetics followed a pseudo-second-order model. At 293 K, the maximum adsorption capacity of CF/poly(NIPAM-co-AAc) was 80.8 mg/g, higher than that of CF (45.6 mg/g) as reflected by kinetics curves. Furthermore, with temperature variation, stepwise adsorption-and-halt behavior was observed at pH 6.0, while swing desorption behavior could be observed at approximately pH 3.0.

Fluorescence studies on the aggregation behaviors of collagen modified with NHS-activated poly(γ-glutamic acid).

The poly(γ-glutamic acid)-NHS (γ-PGA-NHS) esters were used to endow collagen with both of excellent water-solubility and thermal stability via cross-linking reaction between γ-PGA-NHS and collagen. In the present work, the effect of γ-PGA-NHS on the aggregation of collagen molecules was studied by fluorescence techniques. The fluorescence emission spectra of pyrene in collagen solutions and the intrinsic fluorescence emission spectra of collagen suggested different effects of γ-PGA-NHS on collagen molecules: inhibiting aggregation below critical aggregation concentration (CAC) and promoting aggregation above CAC. The two-dimensional (2D) fluorescence correlation spectra indicated that the intermolecular hydrogen bonding and cross-linking between γ-PGA-NHS and collagen would influence the aggregation of collagen molecules. By the ultra-sensitive differential scanning calorimeter (VP-DSC), it was found that the main denaturational transition temperature (Tm2) of modified collagen increased, while its calorimetric enthalpy changes (ΔH2) decreased compared to those of native collagen, further indicating that the modification of γ-PGA-NHS influenced the aggregation of collagen molecules. The study provide useful information for the utilizing and or the processing of water-soluble collagen in aqueous solution in the fields such as cosmetics, health care products, tissue engineering and biomedical materials, etc.