Phage therapy combats pandrug-resistant Acinetobacter baumannii infection safely and efficiently.

Phage therapy offers a promising approach to combat the growing threat of antimicrobial resistance. Yet, key questions remain regarding dosage, administration routes, combination therapy, and the causes of therapeutic failure. In this study, we focused on a novel lytic phage, ФAb4B, which specifically targeted the A. baumannii strains with KL160 CPS, including the pan-drug resistant A. baumannii YQ4. ФAb4B exhibited the ability to effectively inhibit biofilm formation and eradicate mature biofilms independently of dosage. Additionally, it demonstrated a wide spectrum of antibiotic-phage synergy and did not show any cytotoxic or hemolytic effects. Continuous phage injections, both intraperitoneally and intravenously over 7 days, showed no acute toxicity in vivo. Importantly, phage therapy significantly improved neutrophil counts, outperforming ciprofloxacin (CIP). However, excessive phage injections suppressed neutrophil levels. The combinatorial treatment of phage-CIP rescued 91% of the mice, a superior outcome compared to phage alone (67%). The efficacy of the combinatorial treatment was independent of phage dosage. Notably, prophylactic administration of the combinatorial regimen provided no protection, but even when combined with a delayed therapeutic regimen, it saved all the mice. Bacterial resistance to the phage was not a contributing factor to treatment failure. Our preclinical study systematically describes the lytic phage's effectiveness in both in vitro and in vivo settings, filling in crucial details about phage treatment against bacteriemia caused by A. baumannii, which will provide a robust foundation for the future of phage therapy.

Advance on Engineering of Bacteriophages by Synthetic Biology.

Since bacteriophages (phages) were firstly reported at the beginning of the 20th century, the study on them experiences booming-fading-emerging with discovery and overuse of antibiotics. Although they are the hotspots for therapy of antibiotic-resistant strains nowadays, natural phage applications encounter some challenges such as limited host range and bacterial resistance to phages. Synthetic biology, one of the most dramatic directions in the recent 20-years study of microbiology, has generated numerous methods and tools and has contributed a lot to understanding phage evolution, engineering modification, and controlling phage-bacteria interactions. In order to better modify and apply phages by using synthetic biology techniques in the future, in this review, we comprehensively introduce various strategies on engineering or modification of phage genome and rebooting of recombinant phages, summarize the recent researches and potential directions of phage synthetic biology, and outline the current application of engineered phages in practice.

CXCR4 protects bone marrow-derived endothelial progenitor cells against hypoxia through the PI3K/Akt signaling pathway.

The present study aimed to investigate the regulatory mechanism of chemokine (C-X-C motif) receptor 4 (CXCR4) on endothelial progenitor cells (EPCs) through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway under hypoxic conditions. Mononuclear cells were isolated from the bone marrow (BM) of young Sprague-Dawley (SD) rats. Bone marrow-derived endothelial progenitor cells (BM-EPCs) were characterized by using Dil-labeled acetylated low-density lipoprotein (Dil-ac-LDL) and fluorescein isothiocyanate-labeled UEA (FITC-UEA-1). Phenotype identification of BM-EPCs was based on red cytoplasm and green cytomembrane. Flow cytometry was employed to examine the markers CD14, CD34, and KDR. Expression level of the EPC-specific surface marker CD14 was found to be negative, while the expression level of CD34 and KDR was positive. In addition, CXCR4 was stably overexpressed in BM-EPCs after transfection with adenovirus-CXCR4. Cell proliferation, migration and apoptosis abilities were measured through the application of CCK-8, followed by Transwell and flow cytometry assays. The expression level of CXCR4, PI3K and Akt was determined by reverse transcription-quantitative PCR and western blotting assays. Functional experiments demonstrated that hypoxia inhibited BM-EPC proliferation and migration, while accelerating BM-EPC apoptosis. Additionally, CXCR4 was found to promote proliferation and migration, and suppress apoptosis in BM-EPCs with or without hypoxia treatment. Evidence also demonstrated that CXCR4 markedly upregulated the expression levels of PI3K and Akt. Furthermore, PI3K inhibitor (LY294002) and CXCR4 inhibitor (AMD3100) effectively inhibited the proliferation, migration and resistance to apoptosis of CXCR4-mediated BM-EPCs under hypoxic conditions.

Face recognition by applying wavelet subband representation and kernel associative memory.

In this paper, we propose an efficient face recognition scheme which has two features: 1) representation of face images by two-dimensional (2-D) wavelet subband coefficients and 2) recognition by a modular, personalised classification method based on kernel associative memory models. Compared to PCA projections and low resolution "thumb-nail" image representations, wavelet subband coefficients can efficiently capture substantial facial features while keeping computational complexity low. As there are usually very limited samples, we constructed an associative memory (AM) model for each person and proposed to improve the performance of AM models by kernel methods. Specifically, we first applied kernel transforms to each possible training pair of faces sample and then mapped the high-dimensional feature space back to input space. Our scheme using modular autoassociative memory for face recognition is inspired by the same motivation as using autoencoders for optical character recognition (OCR), for which the advantages has been proven. By associative memory, all the prototypical faces of one particular person are used to reconstruct themselves and the reconstruction error for a probe face image is used to decide if the probe face is from the corresponding person. We carried out extensive experiments on three standard face recognition datasets, the FERET data, the XM2VTS data, and the ORL data. Detailed comparisons with earlier published results are provided and our proposed scheme offers better recognition accuracy on all of the face datasets.