A "plug-and-display" nanoparticle based on attenuated outer membrane vesicles enhances the immunogenicity of protein antigens.

As natural nanoparticle, the bacterial outer membrane vesicles (OMV) hold great potential in protein vaccines because of its self-adjuvant properties and good biocompatibility. However, the inherent immunotoxicity seriously hampers the application of OMV as protein antigens delivery carrier. Here, an attenuated OMV was constructed by elimination of the flagella protein from its surface and removal of the phosphate group of LPS at position one via gene-editing strategy.

Programmable Bacteria with Dynamic Virulence Modulation System for Precision Antitumor Immunity.

Engineered bacteria-mediated antitumor approaches have been proposed as promising immunotherapies for cancer. However, the off-target bacterial toxicity narrows the therapeutic window. Living microbes will benefit from their controllable immunogenicity within tumors for safer antitumor applications.

Dual-Engineered Macrophage-Microbe Encapsulation for Metastasis Immunotherapy.

Lung metastases are the leading cause of death among cancer patients. The challenges of inefficient drug delivery, compounded by a robust immunosuppressive microenvironment, make effective treatment difficult. Here, an innovative dual-engineered macrophage-microbe encapsulation (Du-EMME) therapy is developed that integrates modified macrophages and engineered antitumor bacteria.

Camouflaging attenuated Salmonella by cryo-shocked macrophages for tumor-targeted therapy.

Live bacteria-mediated antitumor therapies mark a pivotal point in cancer immunotherapy. However, the difficulty in reconciling the safety and efficacy of bacterial therapies has limited their application. Improving bacterial tumor-targeted delivery while maintaining biosafety is a critical hurdle for the clinical translation of live microbial therapy for cancer.

Combined Cellular Thermometry Reveals That Warms Macrophages by Inducing a Pyroptosis-like Phenotype.

The attenuated VNP20009, enriched in tumors, is known to have antitumor effects and recruit macrophages. Little is known, however, about whether VNP will lead to specific changes in macrophages, , cell temperature. Here, using a real-time wireless multicell thermometry system, we reported for the first time that VNP20009 increases the macrophage temperature by 0.

Macrophage-mediated tumor-targeted delivery of engineered VNP20009 in anti-PD1 therapy against melanoma.

Bacterial antitumor therapy has great application potential given its unique characteristics, including genetic manipulation, tumor targeting specificity and immune system modulation. However, the nonnegligible side effects and limited efficacy of clinical treatment limit their biomedical applications. Engineered bacteria for therapeutic applications ideally need to avoid their accumulation in normal organs and possess potent antitumor activity.

Bulk and Single-Cell Transcriptome Analyses Revealed That the Pyroptosis of Glioma-Associated Macrophages Participates in Tumor Progression and Immunosuppression.

Glioma is the most common of all central nervous system (CNS) malignancies and is associated with a poor prognosis. Pyroptosis has been proven to be associated with the progression of multiple tumors and CNS diseases. However, the relationships between pyroptosis and clinical prognosis and immune cell infiltration are unclear in glioma.

A SARS-CoV-2 oral vaccine development strategy based on the attenuated Salmonella type III secretion system.

Aims: This study aimed to provide a safe, stable and efficient SARS-CoV-2 oral vaccine development strategy based on the type III secretion system of attenuated Salmonella and a reference for the development of a SARS-CoV-2 vaccine.

Methods And Results: The attenuated Salmonella mutant ΔhtrA-VNP was used as a vector to secrete the antigen SARS-CoV-2 based on the type III secretion system (T3SS). The Salmonella pathogenicity island 2 (SPI-2)-encoded T3SS promoter (sifB) was screened to express heterologous antigens (RBD, NTD, S2), and the SPI-2-encoded secretion system (sseJ) was employed to secrete this molecule (psifB-sseJ-antigen, abbreviated BJ-antigen).

Bacterially mediated drug delivery and therapeutics: Strategies and advancements.

It was already clinically apparent 150 years ago that bacterial therapy could alleviate diseases. Recently, a burgeoning number of researchers have been using bacterial regimens filled with microbial therapeutic leads to diagnose and treat a wide range of disorders and diseases, including cancers, inflammatory diseases, metabolic disorders and viral infections. Some bacteria that were designed to have low toxicity and high efficiency in drug delivery have been used to treat diseases successfully, especially in tumor therapy in animal models or clinical trials, thanks to the progress of genetic engineering and synthetic bioengineering.

The Classical Apoptotic Adaptor FADD Regulates Glycolytic Capacity in Acute Lymphoblastic Leukemia.

The Fas-associated death domain (FADD) has long been regarded as a crucial adaptor protein in the extrinsic apoptotic pathway. Despite the non-apoptotic function of FADD is gradually being discovered and confirmed, its corresponding physiological and pathological significance is still unclear. Based on the database of GWAS catalog and GTEx Portal, 17 SNPs associated with leukemia susceptibility were found to be linked to FADD expression.

MAGP2 induces tumor progression by enhancing uPAR-mediated cell proliferation.

Microfibril-associated glycoprotein 2 (MAGP2) plays an important role in regulating cell signaling and acts as a biomarker to predict the prognostic effect of tumor therapy. However, research on MAGP2 mostly focuses on its extracellular signal transmission features, and its potential intracellular function is rarely reported. Here, we reported that intracellular MAGP2 increased the stability of urokinase-type plasminogen activator receptor (uPAR) in the cell by direct interaction which inhibits the lysosomal-mediated degradation of uPAR.

One-pot synthesis of multi-functional cellulose-based ionic conductive organohydrogel with low-temperature strain sensitivity.

The advent of high-performance conductive organohydrogels, which are sustainable in extremely cold environment, has attracted immersing interest in biosensors. In this work, a highly stretchable, self-healable, adhesive and antibacterial cellulose-based ionic conductive organohydrogel with low-temperature strain sensitivity was developed, using in-situ polymerization of acrylamide in glycerol-water with poly (vinyl alcohol), chitosan, FeCl and 2,2,6,6-Tetramethylpiperidine-1-oxyl oxidized cellulose nanofibril (TCNF). Owing to their chemically cross-linked structures and multiple H-bonding networks, the organohydrogel exhibits excellent mechanical properties, such as high stretchability (540 %), high compression strength (0.

Quantification of a cell culture contaminant using 16S rDNA.

In this study, we identified a "black dot"-like cell culture contaminant as a species belonging to the genus of Pusillimonas using 16S rDNA sequencing. Among all antibiotics tested, a combinatorial treatment of ampicillin and gentamicin both at 100 µg/mL was able to eliminate this contaminant. The contaminant was then visualized by fluorescence microscopy using propidium iodide staining and was found inside the cytosol of contaminated A549 cells.

Degradation of phenol via ortho-pathway by Kocuria sp. strain TIBETAN4 isolated from the soils around Qinghai Lake in China.

Based on the feature of high-altitude permafrost topography and the diverse microbial ecological communities of the Qinghai-Tibetan Plateau, soil samples from thirteen different collection points around Qinghai lake were collected to screen for extremophilic strains with the ability to degrade phenol, and one bacterial strain recorded as TIBETAN4 that showed effective biodegradation of phenol was isolated and identified. TIBETAN4 was closely related to Kocuria based on its observed morphological, molecular and biochemical characteristics. TIBETAN4 grew well in the LB medium at pH 7-9 and 0-4% NaCl showing alkalophilicity and halophilism.