A narrow T cell receptor repertoire instructs thymic differentiation of MHC class Ib-restricted CD8+ regulatory T cells.

Although most CD8+ T cells are equipped to kill infected or transformed cells, a subset may regulate immune responses and preserve self-tolerance. Here, we describe a CD8 lineage that is instructed to differentiate into CD8 T regulatory cells (Tregs) by a surprisingly restricted set of T cell receptors (TCRs) that recognize MHC-E (mouse Qa-1) and several dominant self-peptides. Recognition and elimination of pathogenic target cells that express these Qa-1-self-peptide complexes selectively inhibits pathogenic antibody responses without generalized immune suppression. Immunization with synthetic agonist peptides that mobilize CD8 Tregs in vivo efficiently inhibit antigraft antibody responses and markedly prolong heart and kidney organ graft survival. Definition of TCR-dependent differentiation and target recognition by this lineage of CD8 Tregs may open the way to new therapeutic approaches to inhibit pathogenic antibody responses.

Synergistically Promoting Coking Resistance of a La0.4Sr0.4Ti0.85Ni0.15O3-δ Anode by Ru-Doping-Induced Active Twin Defects and Highly Dispersed Ni Nanoparticles.

The development of anodes with highly efficient electrochemical catalysis and good durability is crucial for solid oxide fuel cells (SOFCs). This paper reports a superior Ru-doped La0.4Sr0.4Ti0.85Ni0.15O3-δ (L0.4STN) anode material with excellent catalytic activity and good stability. The doping of Ru can inhibit the agglomeration of in situ-exsolved Ni nanoparticles on the surface and induce the formation of abundant multiple-twinned defects in the perovskite matrix, which significantly increase the concentration of oxygen vacancies. The reduced L0.4STRN (R-L0.4STRN) anode shows an area-specific resistance (ASR) of 0.067 Ω cm2 at 800 °C, which is only about one-third of that of stochiometric R-L0.6STN (0.212 Ω cm2). A single cell with the R-L0.4STRN anode shows excellent stability (∼50 h at 650 °C) in both H2 and CH4. Furthermore, R-L0.4STRN exhibits outstanding resistance to carbon deposition, which can be attributed to the synergistic effect of highly dispersed Ni nanoparticles and active twinned defects induced by Ru doping.

Kinetic Atomic-Scale Reproducibility of the Oxygen Reduction Reaction Process and a Newly Suggested Strong Correlation Descriptor: A Case Study of BaCo0.75Fe0.25O3-δ.

The sluggish oxygen reduction reaction (ORR) is a central issue for energy conversion technologies, particularly in the cathodes of solid oxide fuel cells. The recognition of atomic-level kinetics of the ORR is the key solution. Herein, we take BaCo0.75Fe0.25O3 (BCF) perovskite cathode as a model to investigate the ambiguous ORR mechanism by density function theory and ab initio molecular dynamics. The oxygen dissociation process was found as the rate-determining step, and the performance of BCF series perovskite could be well-characterized by the dissociation barrier energy. Further electronic structure analysis demonstrated that the Pr (Nd)-Odis bond accepted electrons during the oxygen dissociation process, resulting in reduction of the barrier energy. Finally, strong correlations between rare earth 4f electrons and B-site transition metal 3d electrons were found to be another underlying descriptor to determine the electrochemical activity. We expected that the method could be universally applied to design or screen other high-performance perovskite cathodes.

Simultaneous Enhancement of Photoluminescence and Stability of CsPbCl3 Perovskite Enabled by Titanium Ion Dopant.

The application of CsPbCl3 perovskite is limited by the low photoluminescence quantum yield (PLQY), weak luminescence, and unpromising stability. Doping impurity ions has been considered as an effective strategy to tune the optoelectronic performances of perovskite. In this work, heterovalent Ti3+ ions are successfully doped into CsPbCl3 nanocrystals. It is found that Ti3+ ion doping could effectively improve the photoluminescence (PL) performance of CsPbCl3 nanocrystals. Density functional theory (DFT) calculations reveal that Ti3+ ions could introduce more band-edge states around the conduction band minimum of CsPbCl3, which is conducive to release electrons into conduction band. Furthermore, Ti3+ ion doping could inhibit the Cl vacancy concentration in CsPbCl3 and prevent the in-gap state caused by Cl vacancy. Notably, the stability of CsPbCl3 perovskite is greatly improved through Ti3+ ion doping. This work provides a new perspective for improving the optoelectronic properties of all-inorganic perovskites through heterovalent metal ion doping.

Eu-Mn Charge Transfer and the Strong Charge-Spin-Electronic Coupling Behavior in EuMnO3.

Based on first-principles calculations with the DFT + U method, the couplings of lattice, charge, spin, and electronic behaviors underlying the Eu-Mn charge transfer in a strongly correlated system of EuMnO3 were investigated. The potential valence transition from Eu3+/Mn3+ to Eu2+/Mn4+ was observed in a compressed lattice with little distortions, which is achieved under hydrostatic pressure and external strain. The intraplane antiferromagnetism (AFM) of Mn is proved to be instrumental in the emergence of Eu2+. Furthermore, we calculated the magnetic exchange interactions within two equilibrium structures of Eu3+Mn3+O3 and Eu2+Mn4+O3. Mn-Mn ferromagnetic exchange in the ab-plane is enhanced strongly in the Eu2+Mn4+O3 structure, contributing to the existence of mixed states. The versatile electronic structures were obtained within the Eu2+Mn4+O3 phase by imposing different magnetic configurations on the Eu and Mn sublattice, attributed to the coupling of charge transfer and magnetic orderings. It is found that the intraplane ferromagnetic ordering of Mn leads to a metallic electronic structure with the coexistence of Eu2+ and Eu3+, while the intraplane AFM Mn spin ordering leads to insulating states only with Eu2+. Notably, a half-metallic characteristic emerges at the magnetic ground state of CF ordering (C-type AFM for the Eu sublattice and ferromagnetic for the Mn sublattice), which makes such a supposed phase more intriguing than the conventional experimental phase. Additionally, the mixture of delocalized 4f with 5d states of Eu in the background of Mn 3d and O 2p orbitals implies a pathway of Eu 4f 5d ↔ O 2p ↔ Mn 3d for charge transfer between Eu and Mn. Our calculation shows that the Eu-Mn charge transfer could be expected in compressed EuMnO3 and the introduction of Eu2+ 4f states near the Fermi level plays an important role in manipulating the interlinks of charge and spin together with electronic behaviors.

Synthesis of highly fluorescent carbon dots as a dual-excitation rationmetric fluorescent probe for the fast detection of chlorogenic acid.

Nitrogen and sulfur co-doped carbon dots (abbreviated as N,S-CDs) were obtained by two-step hydrothermal reactions using citric acid/sulfamic acid as precursors, polyethyleneimine (PEI) as passivation agent. It was found that the PEI modified CDs with a fluorescence quantum yield of up to 29.1%, showed an obviously enhanced photoluminescence (PL) compared to the initial CDs. Interestingly, when monitored at the fluorescence emission wavelength of 460 nm, the dispersed N,S-CDs solution exhibits only one excitation band peaked at 355 nm, while one aggregated N,S-CDs solution with good water solubility and excellent fluorescence stability possesses two well-separated excitation bands centered at 310 nm/397 nm. When chlorogenic acid (CGA) was added to this aggregated N,S-CDs solution, the excitation peak at 310 nm was obviously reduced due to the inner filter effect (IFE), whereas another peak at 397 nm almost remained constant. Based on the above phenomenon, a dual-excitation ratiometric fluorescent probe for CGA assay was constructed. Under the optimized conditions, the logarithm of the fluorescence intensity ratios (F397/F310) exhibited a good linear correlation with the CGA concentration over a range from 0.33 to 29.70 µg/mL with a detection limit of 0.12 µg/mL. Moreover, the proposed sensing system was applied to determine CGA content in real samples with satisfactory results. The proposed sensing platform provides a new method for the detection of CGA.

Strategy for achieving multiferroic E-type magnetic order in orthorhombic manganites RMnO3 (R = La-Lu).

Based on first-principles calculations, multiferroic properties of orthorhombic manganites (RMnO3, R = La-Lu) with E-type ground state have been achieved by lanthanide contraction (chemical pressure) and/or external strain. Our research demonstrates that a smaller R radius within the octahedral voids in RMnO3 results in the increase in the tilts of the octahedra but only a gentle change in the Jahn-Teller (JT) distortion. The reduction of the intraplane octahedral rotation angle and the narrowed eg states and lifting t2g band edge are mainly responsible for the intraplane magnetic transition from ferromagnetic (La-Gd) to zigzag-like spin arrangement (Ho-Lu). In turn, the center-broken E-type RMnO3 bulk characterizes the dominated electronic polarization behavior, benefiting from their distortion response to small R substitution, which gives rise to the strong magnetoelectricity. Subsequently, we have figured out the strain strategy for obtaining an E-type transition in light rare-earth manganites (La-Gd) by imposing a series of hypothetical strains, where the small intraplane rotation angle (Θ) and large JT distortion favor the small aspect ratios of a/b and c/b, respectively. The strained LaMnO3 and GdMnO3 achieve E-type transitions successfully by imposing a modest compressive strain along the a- and c-axes and remaining free along the b-direction. Simultaneously, their polarization behaviors were comparatively studied. It was found that the size of the A-site rare-earth ions has a great influence on the external strain response, in addition to its effect on the magnetic phase transition.

Fluorescent carbon dots based sensing system for detection of enrofloxacin in water solutions.

Enrofloxacin (ENR) is one of the environmental pollutants need to remove in many wastewater treatment processes. Traditional methods for measuring ENR are often complex and time-consuming. Due to their low cost and high efficiency, fluorescent carbon dots can be used for detecting many pharmaceuticals. In this contribution, nitrogen doped fluorescent carbon dots (N-CDs) were firstly synthesized with a fluorescence quantum yield of 20.5%. The N-CDs can emit strong blue fluorescence when excited at 368 nm and there exist a large amount of carboxyl, hydroxyl and amine groups on their surfaces. In addition, the fluorescence of N-CDs could be quenched in the presence of Cu2+, which could be gradually restored upon adding ENR. Thereby, a rapid and sensitive fluorescent sensing strategy based on the fluorescence recovery of the N-CDs-Cu2+ system was designed for selective detection of ENR. The possible sensing mechanism was also proposed in terms of the results of resonance Rayleigh scattering, UV-vis absorption and Fourier transform infrared (FITR) spectra. Under the optimal condition, a good linear relationship was obtained for ENR determination with concentrations ranging from 1.0 to 15.0 µg·mL-1 and the detection limit of 0.16 µg·mL-1 was achieved. Finally the proposed sensing system was applied for the detection of ENR in real water samples with satisfactory results.

CRISPR-Cas9 HDR system enhances AQP1 gene expression.

Ionizing radiation (IR) isthe primarytherapeutic tool to treat patients with cancerous lesions located in the head and neck. In many patients, IR results in irreversible and severe salivary gland dysfunction or xerostomia. Currently there are no effective treatment options to reduce the effects of xerostomia. More recently, salivary gland gene therapy utilizing the water-specific protein aquaporin 1 (AQP1) has been of great interest to potentially correct salivary dysfunction. In this study, we used CRISPR-Cas9 gene editing along with the endogenous promoter of AQP1 within theHEK293 and MDCK cell lines. The successful integration of the cytomegalovirus (CMV) promoterresultedin a significant increase of AQP1 gene transcription and translation. Additionalfunctional experiments involvingthe MDCK cell line confirmedthat over-expressed AQP1increasedtransmembrane fluid flux indicative of increased intracellular fluid flux. The off-target effect of designed guided RNA sequence was analyzed and demonstrateda high specificity for the Cas9 cleavage. Considering the development of new methods for robust DNA knock-in, our results suggest that endogenous promoter replacement may be a potential treatment forsalivary gland dysfunction.

Human Bocavirus NS1 and NS1-70 Proteins Inhibit TNF-α-Mediated Activation of NF-κB by targeting p65.

Human bocavirus (HBoV), a parvovirus, is a single-stranded DNA etiologic agent causing lower respiratory tract infections in young children worldwide. Nuclear factor kappa B (NF-κB) transcription factors play crucial roles in clearance of invading viruses through activation of many physiological processes. Previous investigation showed that HBoV infection could significantly upregulate the level of TNF-α which is a strong NF-κB stimulator. Here we investigated whether HBoV proteins modulate TNF-α-mediated activation of the NF-κB signaling pathway. We showed that HBoV NS1 and NS1-70 proteins blocked NF-κB activation in response to TNF-α. Overexpression of TNF receptor-associated factor 2 (TRAF2)-, IκB kinase alpha (IKKα)-, IκB kinase beta (IKKß)-, constitutively active mutant of IKKß (IKKß SS/EE)-, or p65-induced NF-κB activation was inhibited by NS1 and NS1-70. Furthermore, NS1 and NS1-70 didn't interfere with TNF-α-mediated IκBα phosphorylation and degradation, nor p65 nuclear translocation. Coimmunoprecipitation assays confirmed the interaction of both NS1 and NS1-70 with p65. Of note, NS1 but not NS1-70 inhibited TNF-α-mediated p65 phosphorylation at ser536. Our findings together indicate that HBoV NS1 and NS1-70 inhibit NF-κB activation. This is the first time that HBoV has been shown to inhibit NF-κB activation, revealing a potential immune-evasion mechanism that is likely important for HBoV pathogenesis.

2C Proteins of Enteroviruses Suppress IKKß Phosphorylation by Recruiting Protein Phosphatase 1.

UNLABELLED: The NF-κB signaling network, which is an ancient signaling pathway, plays a pivotal role in innate immunity and constitutes a first line of defense against invading pathogens, including viruses. However, numerous viruses possess evolved strategies to antagonize the activation of the NF-κB signaling pathway. Our previous study demonstrated that the nonstructural protein 2C of enterovirus 71 (EV71), which is the major pathogen of hand, foot, and mouth disease, inhibits tumor necrosis factor alpha (TNF-α)-mediated activation of NF-κB by suppressing IκB kinase ß (IKKß) phosphorylation. Nevertheless, the mechanism underlying the inhibition of IKKß phosphorylation by EV71 2C remains largely elusive. We demonstrate that EV71 2C interacts with all isoforms of the protein phosphatase 1 (PP1) catalytic subunit (the PP1α, PP1ß, and PP1γ isoforms) through PP1-docking motifs. EV71 2C has no influence on the subcellular localization of PP1. In addition, the PP1-binding-deficient EV71 2C mutant 3E3L nearly completely lost the ability to suppress IKKß phosphorylation and NF-κB activation was markedly restored in the mutant, thereby indicating that PP1 binding is efficient for EV71 2C-mediated inhibition of IKKß phosphorylation and NF-κB activation. We further demonstrate that 2C forms a complex with PP1 and IKKß to dephosphorylate IKKß. Notably, we reveal that other human enteroviruses, including poliovirus (PV), coxsackie A virus 16 (CVA16), and coxsackie B virus 3 (CVB3), use 2C proteins to recruit PP1, leading to the inhibition of IKKß phosphorylation. Our findings indicate that enteroviruses exploit a novel mechanism to inhibit IKKß phosphorylation by recruiting PP1 and IKKß to form a complex through 2C proteins, which ultimately results in the inhibition of the NF-κB signaling pathway. IMPORTANCE: The innate antiviral immunity system performs an essential function in recognizing and eliminating invading viruses. Enteroviruses include a number of important human pathogens, including poliovirus (PV), EV71, and coxsackieviruses (CVs). As 2C is the most conserved and complex nonstructural protein of enteroviruses, its biological function is largely unclear, whereas the 2A and 3C proteinases of enteroviruses are well characterized. We reveal that EV71 2C forms a complex with PP1 and IKKß to maintain IKKß in an unphosphorylated and inactive state, resulting in the inactivation of the TNF-α-mediated NF-κB signaling pathway. We provide evidence that the 2C proteins of the enteroviruses PV, CVA16, and CVB3 suppress IKKß phosphorylation through the same mechanism involving PP1. We demonstrate that enteroviruses exploit a novel mechanism involving PP1 to regulate innate antiviral immunity, and our findings may be particularly important for understanding the pathogenicity of enteroviruses.