Streptococcus pneumoniae endopeptidase O induces trained immunity and confers protection against various pathogenic infections.

Antibiotic resistance and the surge of infectious diseases during the pandemic present significant threats to human health. Trained immunity emerges as a promising and innovative approach to address these infections. Synthetic or natural fungal, parasitic and viral components have been reported to induce trained immunity. However, it is not clear whether bacterial virulence proteins can induce protective trained immunity. Our research demonstrates Streptococcus pneumoniae virulence protein PepO, is a highly potent trained immunity inducer for combating broad-spectrum infection. Our findings showcase that rPepO training confers robust protection to mice against various pathogenic infections by enhancing macrophage functionality. rPepO effectively re-programs macrophages, re-configures their epigenetic modifications and bolsters their immunological responses, which is independent of T or B lymphocytes. In vivo and in vitro experiments confirm that trained macrophage-secreted complement C3 activates peritoneal B lymphocyte and enhances its bactericidal capacity. In addition, we provide the first evidence that granulocyte colony-stimulating factor (G-CSF) derived from trained macrophages plays a pivotal role in shaping central-trained immunity. In summation, our research demonstrates the capability of rPepO to induce both peripheral and central trained immunity in mice, underscoring its potential application in broad-spectrum anti-infection therapy. Our research provides a new molecule and some new target options for infectious disease prevention.

Fabrication of visible-light response cadmium sulfide modified superhydrophobic surface for water resource remediation.

Widespread concern has been attached to the frequent occurrence of pollution by oil slicks and water-soluble pollutants in recent years. The semiconductor photocatalysis is applied to sewage treatment owing to the advantages of energy-conserving and environmental protection. However, its application is limited by the defects of not solving oil slicks and the hard recyclability. In this paper, the high specific surface area and rod-shaped CdS were prepared using template and alkali-treated methods. Next, the alkylated SiO2and alkali-treated CdS were deposited on pure fabric by physical deposition to prepare the multifunctional superhydrophobic fabric. The specific surface area and morphology of alkali-treated CdS were tested by BET specific surface area test and field emission scanning electron microscope. Besides, oil/water separation, water contact angle, and stability test experiments were performed to determine the superhydrophobic performance. Photocatalysis degradation efficiency and cycle degradation stability of multifunctional fabric were characterized by photocatalysis degradation Rh B experiment. Consequently, the alkali-treated CdS displays a high specific surface up to 343 m2g-1. The multifunctional fabric presents excellent superhydrophobic performance with the water contact angle up to 155°. Meanwhile, the water contact angle of multifunctional fabric is always over 150° under various circumstances (acid-base corrosion, soaking time at 100 °C and frictional numbers), indicating that the multifunctional fabric has excellent superhydrophobic stability. Moreover, the fabric also exhibits outstanding photocatalysis performance (the degradation efficiency is 94% after 3 cycles). Our work provides a feasible method for addressing oil slicks on water surface and degrading water-soluble pollutants with extensive application prospects in water resource remediation.

A Streptococcus pneumoniae endolysin mutant protein ΔA146Ply elicits rapid broad-spectrum mucosal protection in mice via upregulation of GPX4 through TLR4/IRG1/NRF2 to alleviate macrophage ferroptosis.

Innovative solutions for rapid protection against broad-spectrum infections are very important in dealing with complex infection environments. We utilized a functionally inactive mutated endolysin protein of Streptococcus pneumoniae (ΔA146Ply) to immunize mice against pneumonic infections by multidrug-resistant bacteria, Candida albicans and influenza virus type A. ΔA146Ply protection relied on both immunized tissue-resident and monocyte-derived alveolar macrophages and inhibited infection induced ferroptosis that upregulated expression of GPX4 (glutathione peroxidase) in alveolar macrophages. Ferroptosis resistance endowed macrophages with enhanced phagocytosis by inhibiting lipid peroxidation during infection. Moreover, we demonstrated ΔA146Ply upregulated GPX4 through the TLR4/IRG1/NRF2 pathway. ΔA146Ply also induced ferroptosis inhibition and phagocytosis improvement in human monocytes. This mode of action is a novel and potentially prophylactic and rapid broad-spectrum anti-infection mechanism. Our study provides new insights into protective interventions that act by regulating ferroptosis to improve multiple pathogen resistance via GPX4 targeting.

Shape controlled synthesis and photoluminescence properties of Eu3+-doped REVO4 nanophosphors.

Eu3+-doped REVO4 nanphosphors were controllably synthesized by an EDTA-mediated hydrothermal method at 180 degrees C using RE(NO3)3 and Na3VO4 as precursors. The obtained products were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectrometry (FTIR), X-ray photoelectron spectra (XPS), and photoluminescence spectroscopy (PL). The XRD results showed that the products were pure tetragonal structure and no other impurity phase appeared. The PL studies demonstrated Eu3+ ions doping effectively enhanced luminescent properties of LaxRE(1-x)VO4 and YxRE(1-x)VO4 nanoparticles, but EU3+ ions doping did not enhance luminescent properties of CexRE(1-x)VO4 (x not equal 0) nanoparticles. The prepared phosphors showed well-defined red luminescence due to radiative transitions from 5D0 to 7F(J) (J = 1,2) levels of Eu3+ ions, respectively. Furthermore, we reported Eu3+-doped CexRE(1-x)VO4 (x not equal 0) phases represented a new class of optically inactive materials.

Structural basis of the novel S. pneumoniae virulence factor, GHIP, a glycosyl hydrolase 25 participating in host-cell invasion.

Pathogenic bacteria produce a wide variety of virulence factors that are considered to be potential antibiotic targets. In this study, we report the crystal structure of a novel S. pneumoniae virulence factor, GHIP, which is a streptococcus-specific glycosyl hydrolase. This novel structure exhibits an α/ß-barrel fold that slightly differs from other characterized hydrolases. The GHIP active site, located at the negatively charged groove in the barrel, is very similar to the active site in known peptidoglycan hydrolases. Functionally, GHIP exhibited weak enzymatic activity to hydrolyze the PNP-(GlcNAc)5 peptidoglycan by the general acid/base catalytic mechanism. Animal experiments demonstrated a marked attenuation of S. pneumoniae-mediated virulence in mice infected by ΔGHIP-deficient strains, suggesting that GHIP functions as a novel S. pneumoniae virulence factor. Furthermore, GHIP participates in allowing S. pneumoniae to colonize the nasopharynx and invade host epithelial cells. Taken together, these findings suggest that GHIP can potentially serve as an antibiotic target to effectively treat streptococcus-mediated infection.

A simple electrochemical aptasensor for ultrasensitive protein detection using cyclic target-induced primer extension.

A simple electrochemical aptasensor was developed for ultrasensitive protein detection by combining a novel strategy of cyclic target-induced primer extension (CTIPE) with an aptamer-hairpin probe and enzyme-amplified electrochemical readout. In the presence of protein target, the immobilized aptamer-hairpin probe recognized the protein to trigger primer extension reaction by target-induced conformational transition, which released the protein from replicated DNA duplex. The released target could cyclically bind with other aptamer-hairpin probes and trigger new primer extension, leading to formation of numerous biotin-tagged DNA duplex, which significantly amplified the protein recognition event and facilitated the subsequent enzymatic signal enhancement, leading to an ultrasensitive electrochemical aptasensor. Using human vascular endothelial growth factor as a model protein, the designed aptasensor could detect protein down to 0.82 pg mL(-1) with a linear range from 1 pg mL(-1) to 1 ng mL(-1). The proposed aptasensor was amenable to quantification of protein in complex biological matrixes, and would become a simple and powerful tool for bioanalysis and clinic diagnostic application.