Antimicrobial activity enabled by chitosan-ε-polylysine-natamycin and its effect on microbial diversity of tomato scrambled egg paste.

For a long time, food spoilage posed a severe impairment on food safety and public health. Although chemical preservatives are commonly used to inhibit spoilage/ pathogenic microbial growth, the disadvantages of a single target, potential toxicity and high dose of use limit the better use of preservatives. In this research, the combination of natural preservatives: Natamycin (Nat), ε-polylysine (ε-PL), and Chitosan (CS) could achieve an excellent antimicrobial effect including bacteria and fungi, and reduce the usage of a single preservative. Compound preservatives could destroy microbial morphology and damage the integrity of the cell wall/membrane by leakage of protein and alkaline phosphatase (AKP). Besides, high-throughput sequencing revealed that compound preservatives could decrease microbial diversity and richness, especially, Pseudomonas, Acinetobacter, Fusarium, and Aspergillus. Therefore, the combination of 1/8 × MIC CS, 1/4 × MIC ε-PL, and 1/2 × MIC Nat can achieve an excellent antibacterial effect, providing new ideas for food preservation.

Recent advances in nanomaterial-mediated bacterial molecular action and their applications in wound therapy.

Because of the multi-pathway antibacterial mechanisms of nanomaterials, they have received widespread attention in wound therapy. However, owing to the complexities of bacterial responses toward nanomaterials, antibacterial molecular mechanisms remain unclear, making it difficult to rationally design highly efficient antibacterial nanomaterials. Fortunately, molecular dynamics simulations and omics techniques have been used as effective methods to further investigate the action targets of nanomaterials. Therefore, the review comprehensively analyzes the antibacterial mechanisms of nanomaterials from the morphology-dependent antibacterial activity and physicochemical/optical properties-dependent antibacterial activity, which provided guidance for constructing excellently efficient and broad-spectrum antibacterial nanomaterials for wound therapy. More importantly, the main molecular action targets of nanomaterials from the membranes, DNA, energy metabolism pathways, oxidative stress defense systems, ribosomes, and biofilms are elaborated in detail. Furthermore, nanomaterials used in wound therapy are reviewed and discussed. Finally, future directions of nanomaterials from mechanisms to nanomedicine are further proposed.

Correction: Liu et al. Functionalized MoS2 Nanoflowers with Excellent Near-Infrared Photothermal Activities for Scavenging of Antibiotic Resistant Bacteria. Nanomaterials 2021, 11, 2829.

In the original publication [...].

Recent development in antibacterial activity and application of nanozymes in food preservation.

Nanozymes with excellent broad-spectrum antibacterial properties offers an alternative strategy for food preservation. This review comprehensively summarized the antibacterial mechanisms of nanozymes, including the generation of reactive oxygen species (ROS) and the destruction of biofilms. Besides, the primary factors (size, morphology, hybridization, light, etc.) regulating the antibacterial activity of different types of nanozymes were highlighted in detail, which provided effective guidance on how to design highly efficient antibacterial nanozymes. Moreover, this review presented elaborated viewpoints on the unique applications of nanozymes in food preservation, including the selection of nanozymes loading matrix, fabrication techniques of nanozymes-based antibacterial films/coatings, and the recent advances in the application of nanozymes-based antibacterial films/coatings in food preservation. In the end, the safety issues of nanozymes have also been mentioned. Overall, this review provided new avenues in the field of food preservation and displayed great prospects.

Specifically functionalized MTT-Ag NP/SA film sensor for the ultrasensitive detection of Hg2+ in lettuce samples.

In the present study, highly efficient 5-Methyl-1,3,4-thiadiazole-2-thiol-modified silver nanoparticles (MTT-Ag NPs) were successfully synthesized and could be used for convenient and sensitive detection of Hg2+. MTT acts as a protective agent by forming Ag-S bonds with Ag NPs, meantime, MTT can also be captured Hg2+ through NN bonds. Furthermore, to improve the sustainability and stability of MTT-Ag NPs, sodium alginate (SA) was used as a substrate material for the formation of SA-MTT-Ag NPs films. As expected, SA-MTT-Ag NPs could be stored for more than 180 days at room temperature. When used SA-MTT-Ag NPs thin films as colourimetric sensors for detection of Hg2+ in lettuce, the low detection limit could be down to 0.22 µM (44 ppb) with wide linear range (0-1 µM and 1-150 µM) and good recovery (96.25 % - 98.75 %). Therefore, the method enables highly selective and efficient monitoring of Hg2+ in food samples.

Transcriptomic and metabolomic investigation of molecular inactivation mechanisms in Escherichia coli triggered by graphene quantum dots.

Graphene quantum dots (GQDs), a novel broad-spectrum antibacterial agent, are considered potential candidates in the field of biomedical and food safety due to their outstanding antimicrobial properties and excellent biocompatibility. To uncover the molecular regulatory mechanisms underlying the phenotypes, the overall regulation of genes and metabolites in Escherichia coli (E. coli) after GQDs stimulation was investigated by RNA-sequencing and LC-MS. Gene transcription and metabolite expression related to a series of crucial biomolecular processes were influenced by the GQDs stimulation, including biofilm formation, bacterial secretion system, sulfur metabolism and nitrogen metabolism, etc. This study could provide profound insights into the GQDs stress response in E. coli, which would be useful for the development and application of GQDs in food safety.

Based on multi-omics technology study the antibacterial mechanisms of pH-dependent N-GQDs beyond ROS.

Currently, graphene quantum dots (GQDs) are widely used as antibacterial agents, and their effects are dependent on the reactive oxygen species (ROS) generated by photodynamic and peroxidase activities. Nevertheless, the supply of substrates or light greatly limits GQDs application. Besides, due to compensatory mechanisms in bacteria, comprehensive analysis of the molecular mechanism underlying the effects of GQDs based on cellular-level experiments is insufficient. Therefore, N-GQDs with inherent excellent, broad-spectrum antibacterial efficacy under acidic conditions were successfully synthesized. Then, via multi-omics analyses, the antibacterial mechanisms of the N-GQDs were found to not only involve generation ROS but also be associated with changes in osmotic pressure, interference with nucleic acid synthesis and inhibition of energy metabolism. More surprisingly, the N-GQDs could destroy intracellular acid-base homeostasis, causing bacterial cell death. In conclusion, this study provides important insights into the antibacterial mechanism of GQDs, offering a basis for the engineering design of antibacterial nanomaterials.

Clinical effectiveness and reliability of linezolid in the treatment of pulmonary tuberculosis complicated with severe pneumonia: a meta-analysis.

OBJECTIVE: To systematically evaluate the clinical effect and reliability of linezolid in the treatment of pulmonary tuberculosis complicated with severe pneumonia. METHODS: A comprehensive search was conducted to screen the published literature on linezolid therapy in pulmonary tuberculosis complicated with severe pneumonia in PubMed, Embase, Web of Science, Cochrane Library, and published databases of China National Knowledge Infrastructure. After screening the internal data of the literature, the quality of the literature was assessed uniformly. RevMan5.3 was used for meta-analysis. RESULTS: The search identified 1202 clinical patients in 24 articles. Meta-analysis results revealed that linezolid treatment was associated with better bacterial clearance rate (OR=3.66 [2.41, 5.58], P<0.001) and superior total clinical effective rate (OR=5.80 [3.92, 8.58], P<0.001) in patients. The linezolid treatment resulted in lower levels of serum inflammatory factors TNF-α (WMD=-10.75 [-13.63, -7.87], P<0.001), IL6 (WMD=-10.16 [-13.50, -6.82], P<0.001), and IL8 (WMD=-8.31 [-10.41, -6.21], P<0.001). There was no obvious distinction in the occurrence of adverse reactions between the linezolid group and the control group (OR=1.34 [0.86, 2.08], P=0.19). CONCLUSION: Linezolid combined with conventional anti-tuberculosis treatment has a better bacterial clearance rate and clinical total effective rate than conventional anti-tuberculosis programs with reliable safety.

Construction Of High Loading Natural Active Substances Nanoplatform and Application in Synergistic Tumor Therapy.

Background: Natural bioactive substances have been widely studied for their superior anti-tumor activity and low toxicity. However, natural bioactive substances suffer from poor water-solubility and poor stability in the physiological environment. Therefore, to overcome the drawbacks of natural bioactive substances in tumor therapy, there is an urgent need for an ideal nanocarrier to achieve high bioactive substance loading with low toxicity. Materials and Methods: Face-centered cubic hollow mesoporous Prussian Blue (HMPB) NPs were prepared by stepwise hydrothermal method. Among them, PVP served as a protective agent and HCl served as an etching agent. Firstly, MPB NPs were obtained by 0.01 M HCl etching. Then, the highly uniform dispersed HMPB NPs were obtained by further etching with 1 M HCl. Results: In this work, we report a pH-responsive therapeutic nanoplatform based on HMPB NPs. Surprisingly, as-prepared HMPB NPs with ultra-high bioactive substances loading capacity of 329 µg mg-1 owing to the large surface area (131.67 m2 g-1) and wide internal pore size distribution (1.8-96.2 nm). Moreover, with the outstanding photothermal conversion efficiency of HMPB NPs (30.13%), natural bioactive substances were released in the tumor microenvironment (TME). HMPB@PC B2 achieved excellent synergistic therapeutic effects of photothermal therapy (PTT) and chemotherapy (CT) in vivo and in vitro without causing any extraneous side effects. Conclusion: A biocompatible HMPB@PC B2 nanoplatform was constructed by simple physical adsorption. The in vitro and in vivo experiment results demonstrated that the synergy of PTT/CT provided excellent therapeutic efficiency for cervical cancer without toxicity. Altogether, as-designed nanomedicines based on natural bioactive substances may be provide a promising strategy for cancer therapy.

Exosomal microRNA-25 released from cancer cells targets SIK1 to promote hepatocellular carcinoma tumorigenesis.

BACKGROUND: Hepatocellular carcinoma (HCC) is recognized as a leading cause of cancer-associated fatality worldwide. Our study here aimed to probe the mechanism by which exosomes secreted by CSQT-2, an HCC cell line, affected the progression of HCC. METHODS: Exosomes were extracted from CSQT-2 cells. Colony formation, Transwell, sphere formation and flow cytometric analyses were applied to assess cell biological activities. Microarray analysis detected the change of microRNA (miRNA) expression after exosome treatment, followed by RT-qPCR validation. Luciferase reporter was applied to detect the binding between SIK1 and miR-25. Xenograft studies in nude mice manifested tumor growth and metastatic ability of miR-25 and SIK1. RESULTS: The exosome treatment enhanced cell malignant phenotype in vitro and tumor growth and liver and lung metastases in vivo. The exosomes elevated miR-25 expression in HCC cells. miR-25 targeted SIK1 which was decreased in the exosomes-treated cells. miR-25 inhibitor reduced cell malignant phenotype and attenuated tumorigenesis and metastasis in vivo. SIK1 silencing reversed the effect of miR-25 inhibitor. The exosome treatment potentiated the Wnt/ß-catenin pathway in cells, whereas miR-25 inhibitor blunted the pathway activity. CONCLUSION: MiR-25 shuttled through CSQT-2-derived exosomes promoted the development of HCC by reducing SIK1 expression and potentiating the Wnt/ß-catenin pathway.

Functionalized MoS2 Nanoflowers with Excellent Near-Infrared Photothermal Activities for Scavenging of Antibiotic Resistant Bacteria.

Presently, antibiotic resistant bacteria (ARB) have been commonly found in environment, such as air, soil and lakes. Therefore, it is urgent and necessary to prepare antimicrobial agents with excellent anti-antibiotic resistant bacteria. In our research, poly-ethylene glycol functionalized molybdenum disulfide nanoflowers (PEG-MoS2 NFs) were synthesized via a one-step hydrothermal method. As-prepared PEG-MoS2 NFs displayed excellent photothermal conversion efficiency (30.6%) and photothermal stability. Under 808 nm NIR laser irradiation for 10 min, the inhibition rate of tetracycline-resistant Bacillus tropicalis and Stenotrophomonas malphilia reached more than 95% at the concentration of 50 µg/mL. More interestingly, the photothermal effect of PEG-MoS2 NFs could accelerate the oxidation of glutathione, resulting in the rapid death of bacteria. A functionalized PEG-MoS2 NFs photothermal anti-antibiotic resistant system was constructed successfully.

Integrated 16S rRNA Gene Sequencing and LC-MS Analysis Revealed the Interplay Between Gut Microbiota and Plasma Metabolites in Rats With Ischemic Stroke.

Gut microbiome and plasma metabolome serve a role in the pathogenesis of ischemic stroke (IS). However, the relationship between the microbiota and metabolites remains unclear. This study aimed to reveal the specific asso-ciation between the microbiota and the metabolites in IS using integrated 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) analysis. Male Sprague Dawley (SD) rats were divided into three groups: normal group (n = 8, Normal), model group (n = 9, IS), and sham-operated group (n = 8, Sham). Rats in the IS group were induced by middle cerebral artery occlusion (MCAO), and rats in the Sham group received an initial anesthesia and neck incision only. A neurological function test and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to assess the IS rat model. Then, the plasma samples were analyzed using untargeted LC-MS. The cecum samples were collected and analyzed using 16S rRNA sequencing. Pearson correlation analysis was performed to explore the association between the gut microbiota and the plasma metabolites. The 16S rRNA sequencing showed that the composition and diversity of the microbiota in the IS and control rats were significantly different. Compared with the Sham group, the abundance of the Firmicutes phylum was decreased, whereas Proteobacteria and Deferribacteres were increased in the IS group. Ruminococcus_sp_15975 and Lachnospiraceae_UCG_001 might be considered as biomarkers for the IS and Sham groups, respectively. LC-MS analysis revealed that many metabolites, such as L-leucine, L-valine, and L-phenylalanine, displayed different patterns between the IS and Sham groups. Pathway analysis indicated that these metabolites were mainly involved in mineral absorption and cholinergic synapse. Furthermore, integrated analysis correlated IS-related microbes with metabolites. For example, Proteobacteria were positively correlated with L-phenylalanine, while they were negatively correlated with eicosapentaenoic acid (EPA). Our results provided evidence of the relationship between the gut microbiome and plasma metabolome in IS, suggesting that these microflora-related metabolites might serve as potential diagnostic and therapeutic markers.

Visual determination of azodicarbonamide in flour by label-free silver nanoparticle colorimetry.

A very practical and competitive sensing strategy for the detection of azodicarbonamide in flour samples was developed by using label-free Ag NPs as a colorimetric probe. Well-dispersed Ag NPs in suspension can form aggregates upon reacting with glutathione (GSH) via Ag-SH covalent bonds and electrostatic attraction, with the color changing from bright yellow to red. However, azodicarbonamide can oxidize the -SH of GSH, preventing the aggregation of Ag NPs. Under the optimum conditions, the A550/A398 of Ag NPs is linearly related to the concentration of azodicarbonamide in the range of 0.33 µM to 1.7 µM. The proposed method can be used for the detection of azodicarbonamide in flour, with a detection limit of 0.09 µM and recovery between 95% and 97.4% (RSD < 6%). When the azodicarbonamide concentration reaches 0.33 µM, the color change can be detected by the naked eye.

Exosomes secreted by chronic hepatitis B patients with PNALT and liver inflammation grade ≥ A2 promoted the progression of liver cancer by transferring miR-25-3p to inhibit the co-expression of TCF21 and HHIP.

OBJECTIVES: The current study aimed to investigate the mechanism by which exosomes secreted by CHB patients with PNALT and liver inflammation grade (≥A2) affected the development of liver cancer. MATERIALS AND METHODS: Gene expression was assessed by RT-PCR, Western blotting and immunohistochemistry. CCK-8, colony formation, transwell, scratch-wound and flow cytometry assays were used to detect cell viability, proliferation, apoptosis and metastasis. The interaction of TCF21 and HHIP was assessed by co-immunoprecipitation assay. Luciferase reporter was used to detect the combination of TCF21/HHIP and miR-25-3p. Xenograft studies in nude mice manifested tumour growth ability of miR-25-3p. Bioinformatics analyses were conducted using TargetScan, EVmiRNA, TCGA, GEO, DAVID, COEXPEDIA, UALCAN, UCSC and the Human Protein Atlas databases. RESULTS: CHB-PNALT-Exo (≥A2) promoted the proliferation and metastasis of HepG2.2.15 cells. miR-25-3p was upregulated in CHB-PNALT-Exo (≥A2). miR-25-3p overexpression promoted cell proliferation and metastasis and was related to poor survival in patients with CHB-PNALT (≥A2). The cell proliferation- and metastasis-promoting functions of CHB-PNALT-Exo (≥A2) were abolished by miR-25-3p inhibitors. TCF21 directly interacted with HHIP. Inhibition of TCF21 or HHIP promoted cell proliferation and metastasis. Knockdown of TCF21 or HHIP counteracted the effects of CHB-PNALT-Exo (≥A2) containing miR-25-3p inhibitor on cell proliferation, metastasis and the expression of Ki67, E-cadherin and caspase-3/-9. CONCLUSIONS: Transfer of miR-25-3p by CHB-PNALT-Exo promoted the development of liver cancer by inhibiting the co-expression of TCF21 and HHIP.

Modulators of microglia activation and polarization in ischemic stroke (Review).

Ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. As the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses. In response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the anti­inflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. It has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. In addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified.

LncRNA HOTAIRM1 promotes osteogenesis by controlling JNK/AP-1 signalling-mediated RUNX2 expression.

Mesenchymal stem cells (MSCs) have potential ability to differentiate into osteocytes in response to in vitro specific induction. However, the molecular basis underlying this biological process remains largely unclear. In this study, we identify lncRNA HOTAIRM1 as a critical regulator to promote osteogenesis of MSCs. Loss of HOTAIRM1 significantly inhibits the calcium deposition and alkaline phosphatase activity of MSCs. Mechanistically, we find that HOTAIRM1 positively modulates the activity of JNK and c-Jun, both of which are widely accepted as crucial regulators of osteogenic differentiation. More importantly, c-Jun is found to be functionally involved in the regulation of RUNX2 expression, a master transcription factor of osteogenesis. In detail, c-Jun can help recruit the acetyltransferase p300 to RUNX2 promoter, facilitating acetylation of histone 3 at K27 site, therefore epigenetically activating RUNX2 gene transcription. In summary, this study highlights the functional importance of HOTAIRM1 in regulation of osteogenesis, and we characterize HOTAIRM1 as a promising molecular target for bone tissue repair and regeneration.