Joint engineering of SACE_Lrp and its target MarR enhances the biosynthesis and export of erythromycin in Saccharopolyspora erythraea.

The Lrp and MarR families are two groups of transcriptional regulators widely distributed among prokaryotes. However, the hierarchical-regulatory relationship between the Lrp family and the MarR family remains unknown. Our previous study found that an Lrp (SACE_Lrp) from Saccharopolyspora erythraea indirectly repressed the biosynthesis of erythromycin. In this study, we characterized a novel MarR family protein (SACE_6745) from S. erythraea, which is controlled by SACE_Lrp and plays a direct regulatory role in erythromycin biosynthesis and export. SACE_Lrp directly regulated the expression of marR by specifically binding a precise site OM (5'-CTCCGGGAACCATT-3'). Gene disruption of marR increased the production of erythromycin by 45% in S. erythraea A226. We found that MarR has direct DNA-binding activity for the promoter regions of the erythromycin biosynthetic genes, as well as an ABC exporter SACE_2701-2702 which was genetically proved to be responsible for erythromycin efflux. Disruption of SACE_Lrp in industrial S. erythraea WB was an efficient strategy to enhance erythromycin production. Herein, we jointly engineered SACE_Lrp and its target MarR by deleting marR in WBΔSACE_Lrp, resulting in 20% increase in erythromycin yield in mutant WBΔLrpΔmarR compared to WBΔSACE_Lrp, and 39% to WB. Overall, our findings provide new insights into the hierarchical-regulatory relationship of Lrp and MarR proteins and new avenues for coordinating antibiotic biosynthesis and export by joint engineering regulators in actinomycetes. KEY POINTS: • The hierarchical-regulatory relationship between SACE_Lrp and MarR was identified. • MarR directly controlled the expression of erythromycin biosynthesis and export genes. • Joint engineering of SACE_Lrp-MarR regulatory element enhanced erythromycin production.

Antibacterial activity of chlorogenic acid-loaded SiO2 nanoparticles caused by accumulation of reactive oxygen species.

Diseases caused by pathogenic bacilli pose an increasing threat to human health. A common feature of these bacteria is a complete cell wall; therefore, drugs that can penetrate this protective barrier could be used as a novel approach for treating these infections. Here we present a simple method for synthesizing a silica mesoporous material loaded with cadmium selenide (CdSe) and chlorogenic acid. Using UV-visible, fluorescence, and infrared imaging in combination with transmission electron microscopy, it was shown that CdSe and chlorogenic acid could be successfully embedded in the mesopores of silica nanoparticles (CSC NPs), and these NPs presented with a strong fluorescence, uniform size, and good dispersion. Additionally, the results of these analyses indicated that the fluorescence of the CSC NPs was localized within the cells of Escherichia coli and Bacillus subtilis, signifying that these NPs could breach the cell wall and enter the cells of these two bacilli. Additional assessments found that these CSC NPs inhibited the proliferation of the bacteria by disrupting the cell wall, and this was most likely due to the overproduction of reactive oxygen species induced by chlorogenic acid. Importantly, histopathology analysis indicated that the CSC NPs had limited side effects and high biocompatibility.

Massilia atriviolacea sp. nov., a dark purple-pigmented bacterium isolated from soil.

A bacterial strain, designated SODT, with Gram-stain-negative and motile rod-shaped cells, was isolated from soil in Hefei, PR China, and was characterized using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SODT belonged to the genus Massilia and showed the highest similarities to Massilia violaceinigra B2T (99.3 %), followed by Massilia glaciei B448-2T (98.7 %), Massilia eurypsychrophila CGMCC 1.12828T (98.6 %) and Rugamonas rubra CCM3730T (97.8 %). Average nucleotide identity and digital DNA-DNA hybridization values between genome sequences of strain SODT and the closely related species ranged from 77.1 to 89.3% and from 22.2 to 34.7 %. The DNA G+C content of strain SODT was 65.4 mol%. Strain SODT contained Q-8 as the major ubiquinone and the dominant fatty acids were summed feature 3 (C16 : 1ω7c and/or C15 : 0iso 2-OH; 58.5 %), C16 : 0 (26.8 %) and C18 : 1ω7c (5.0 %). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. On the basis of the evidence presented in this study, strain SODT represents a novel species of the genus Massilia, for which the name Massiliaatriviolacea sp. nov. is proposed. The type strain is SODT (=KCTC 62720T=LMG 30840T).

Characterization and engineering of the Lrp/AsnC family regulator SACE_5717 for erythromycin overproduction in Saccharopolyspora erythraea.

In this work, we found that the Lrp/AsnC family protein SACE_5717 negatively regulated erythromycin biosynthesis in S. erythraea. Disruption of SACE_5717 led to a 27% improvement in the yield of erythromycin in S. erythraea A226. SACE_5717 directly repressed its own gene expression, as well as that of the adjacent gene SACE_5716 by binding to the target sequence 5'-GAACGTTCGCCGTCACGCC-3'. The predicted LysE superfamily protein SACE_5716 directly influenced the export of lysine, histidine, threonine and glycine in S. erythraea. Arginine, tyrosine and tryptophan were characterized as the effectors of SACE_5717 by weakening the binding affinity of SACE_5717. In the industrial S. erythraea WB strain, deletion of SACE_5717 (WBΔSACE_5717) increased erythromycin yield by 20%, and by 36% when SACE_5716 was overexpressed in WBΔSACE_5717 (WBΔSACE_5717/5716). In large-scale 5-L fermentation experiment, erythromycin yield in the engineered strain WBΔSACE_5717/5716 reached 4686 mg/L, a 41% enhancement over 3323 mg/L of the parent WB strain.

Leucobacter triazinivorans sp. nov., a s-triazine herbicide prometryn-degrading bacterium isolated from sludge.

A Gram-stain-positive, rod-shaped, non-motile bacterial strain, designated JW-1T, was isolated from activated sludge collected from the outlet of an aeration tank in a prometryn-manufacturing plant, located in Binzhou City, Shandong province, PR China. Phylogenetic analysis, based on 16S rRNA gene sequences, indicated that strain JW-1T belongs to the genus Leucobacter and its closest neighbours are 'Leucobacter kyeonggiensis' F3-P9 (98.95 % similarity), Leucobacter celer subsp. astrifaciens CBX151T (98.62 %), Leucobacter celer subsp. celer NAL101T (98.53 %), Leucobacter chromiiresistens JG31T (97.86 %) and Leucobacter chironomi DSM 19883T (97.37 %). DNA-DNA hybridization values with the above strains were <55 %. The DNA G+C content of strain JW-1T was 72.6 mol%. The major fatty acids of strain JW-1T were iso-C16 : 0, anteiso-C15 : 0, anteiso-C17 : 0 and iso-C15 : 0. The predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol and glycolipid. The predominant menaquinone was MK-11. The cell wall amino acids were 2,4-diaminobutyric acid, alanine, glutamic acid, glycine and threonine. Based on the molecular and chemotaxonomic data, as well as the physiological and biochemical characteristics, strain JW-1T is considered to represent a novel species of the genus Leucobacter, for which the name Leucobacter triazinivorans is proposed. The type strain is JW-1T (=DSM 105188T=LMG 30083T).

Caulobacter rhizosphaerae sp. nov., a stalked bacterium isolated from rhizosphere soil.

The Gram-reaction-negative, aerobic, white- to pale-yellow-coloured and rod-shaped bacterium with a single polar flagellum or a stalk, designated strain 7F14T, was isolated from rhizosphere soil of cultivated watermelon (Citrullus lanatus) collected from Hefei, China. Growth of strain 7F14T was observed at pH 6.0-9.0, 10-30 °C and in the presence of 0-1 % (w/v) NaCl. Cells were catalase-negative and oxidase-positive. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain 7F14T formed a phyletic lineage within the genus Caulobacter of the family Caulobacteraceae and showed the highest 16S rRNA gene sequence similarities to Caulobacter henricii ATCC 15253T (98.66 %), Caulobacter segnis ATCC 21756T (98.27 %), Caulobacter vibrioides CB51T (97.92 %) and Caulobacter flavus RHGG3T (97.44 %). The G+C content of the genomic DNA was 68.6 mol%. Strain 7F14T contained Q-10 as the sole ubiquinone and 11-methyl C18 : 1ω7c, C18 : 1ω7c, C16 : 0 and summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH) as the major fatty acids. The polar lipids profile consisted of phosphatidylglycerol, an unknown phosphoglycolipid, five unknown glycolipids, an unknown phospholipid and three unknown lipids. DNA-DNA relatedness values to the most closely related type strains Caulobacter henricii DSM 4730T and Caulobacter segnis DSM 7131T were 26.0 and 19.7 %, respectively. Based on unique phenotypic traits, and phylogenetic, chemotaxonomic and DNA-DNA hybridization results, strain 7F14T should be classified as a representative of a novel species of the genus Caulobacter, for which the name Caulobacter rhizosphaerae sp. nov. is proposed. The type strain is 7F14T (=CGMCC 1.15915T=KCTC 52515T).

Mucilaginibacter rubeus sp. nov., isolated from rhizosphere soil.

A Gram-stain-negative, aerobic, non-motile, rod-shaped and non-spore-forming bacterium, designated EF23T, was isolated from rhizosphere soil of watermelon. Growth of strain EF23T was observed at 10-37 °C, at pH 5.0-9.0 and in the presence of 0-0.5 % (w/v) NaCl. Strain EF23T contained menaquinone 7 (MK-7) as the major isoprenoid quinone, and summed feature 3 (C16:1ω7c and/or iso-C15 : 0 2-OH), iso-C15 : 0, C16 : 0 and iso-C17 : 0 3-OH as the major fatty acids. Phosphatidylethanolamine was identified as the major polar lipid. The genomic DNA G+C content of strain EF23T was 43.7 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain EF23T was most closely related to Mucilaginibacter gossypii Gh-67T (98.9 % similarity) and Mucilaginibacter gossypiicola Gh-48T (97.6 %). DNA-DNA relatedness values between strain EF23T and M. gossypii KCTC 22380T and M. gossypiicola KCTC 22379T were 31.6 and 53.7 %. On the basis of the evidence presented in this polyphasic taxonomic study, strain EF23T is considered to represent a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter rubeus sp. nov. is proposed. The type strain is EF23T (=CGMCC 1.15913T=KCTC 52516T).

Massilia buxea sp. nov., isolated from a rock surface.

A Gram-stain-negative, rod-shaped and motile bacterial strain, designated A9T, was isolated from the surface of rock collected from the shore of Nvshan lake in Mingguang, Anhui province, China. Phylogenetic analysis based on 16S rDNA sequence data showed that strain A9T was affiliated with the genus Massilia and showed the highest sequence similarities to Massilia plicata KCTC 12344T (98.8 %) and Massilia lurida CGMCC 1.10822T (97.9 %). The major fatty acids (>5 %) were summed feature 3 (C16 : 1ω7c and/or C15 : 0 iso 2-OH), C16 : 0 and C18 : 1ω7c. Strain A9T contained Q-8 as the predominant ubiquinone and diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and an unidentified aminophospholipid as the predominant polar lipids. The DNA G+C content was 69.9 mol%. Mean DNA-DNA relatedness values between strain A9T and its closest phylogenetic relatives, M. plicata KCTC 12344T and M. lurida CGMCC 1.10822T, were 38.8 % and 23.23 %, respectively. On the basis of the results obtained in this study, strain A9T is considered to represent a novel species of the genus Massilia, for which the name Massilia buxea sp. nov. is proposed. The type strain is A9T (=DSM 103547T=CGMCC 1.15931T=KCTC 52429T).

Anti-tumor activity and mechanism of apoptosis of A549 induced by ruthenium complex.

Two new ruthenium (II) polypyridyl complexes [Ru(MeIm)4(pip)]2+ (1) and [Ru(MeIm)4(4-npip)]2+ (2) were synthesized under the guidance of computational studies (DFT). Their binding property to human telomeric G-quadruplex studied by UV-Vis absorption spectroscopy, the fluorescent resonance energy transfer (FRET) melting assay and circular dichroism (CD) spectroscopy for validating the theoretical prediction. Both of them were evaluated for their potential anti-proliferative activity against four human tumor cell lines. Complex 2 shows growth inhibition against all the cell lines tested, especially the human lung tumor cell (A549). The RTCA analysis not only validated the inhibition activity but also showed the ability of reducing A549 cells' migration. DNA-flow cytometric analysis, mitochondrial membrane potential (ΔΨm) and the scavenger measurements of reactive oxygen species (ROS) analysis carried out to investigate the mechanism of cell growth inhibition and apoptosis-inducing effect of complex 2. The results demonstrated that complex 2 induces tumor cells apoptosis by acting on both mitochondrial homeostasis destruction and death receptor signaling pathways. And those suggested that complex 2 could be a candidate for further evaluation as a chemotherapeutic agent against human tumor.

Cupriavidus nantongensis sp. nov., a novel chlorpyrifos-degrading bacterium isolated from sludge.

A Gram-stain-negative, aerobic, coccoid to small rod-shaped bacterium, designated X1T, was isolated from sludge collected from the vicinity of a pesticide manufacturer in Nantong, Jiangsu Province, China. Based on 16S rRNA gene sequence analysis, strain X1T belonged to the genus Cupriavidus, and was most closely related to Cupriavidus taiwanensis LMG 19424T (99.1 % 16S rRNA gene sequence similarity) and Cupriavidus alkaliphilus LMG 26294T (98.9 %). Strain X1T showed 16S rRNA gene sequence similarities of 97.2-98.2 % with other species of the genus Cupriavidus. The major cellular fatty acids of strain X1T were C16 : 0, C16 : 1ω7c and/or iso-C15 : 0 2-OH (summed feature 3), C18 : 1ω7c and C17 : 0 cyclo, and the major respiratory quinone was ubiquinone Q-8. The major polar lipids of strain X1T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, aminophospholipid, phospholipid and hydroxyphosphatidylethanolamine. The DNA G+C content was 66.6 mol%. The DNA-DNA relatedness values of strain X1T with the five reference strains C. taiwanensis LMG 19424T, C. alkaliphilus LMG 26294T, Cupriavidus necator LMG 8453T, Cupriavidus gilardii LMG 5886T and 'Cupriavidus yeoncheonense' KCTC 42053 were lower than 70 %. The results obtained from phylogenetic analysis, phenotypic characterization and DNA-DNA hybridization indicated that strain X1T should be proposed to represent a novel species of the genus Cupriavidus, for which the name Cupriavidus nantongensis sp. nov. is proposed. The type strain is X1T (=KCTC 42909T=LMG 29218T).

Caulobacter flavus sp. nov., a stalked bacterium isolated from rhizosphere soil.

A Gram-stain-negative, aerobic, yellow-pigmented and rod-shaped bacterium with a single polar flagellum or a stalk, designated strain RHGG3T, was isolated from rhizosphere soil of cultivated watermelon (Citrullus lanatus) collected from Hefei, China. Optimal growth of strain RHGG3T was observed at pH 7.0 and 28-30 °C. Cells were catalase-positive and oxidase-negative. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain RHGG3T belonged to the genus Caulobacter and showed the highest 16S rRNA gene sequence similarities to Caulobacter segnis ATCC 21756T (98.6 %), Caulobacter vibrioides CB51T (98.3 %) and Caulobacter henricii ATCC 15253T (97.2 %). The G+C content of the genomic DNA was 70 mol%. Strain RHGG3T contained Q-10 as the sole ubiquinone and the major fatty acids (>8 %) were 11-methyl C18 : 1ω7c, C18 : 1ω7c, C16 : 0, C15 : 0 and summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH). The polar lipids were various unknown glycolipids, phosphatidylglycerol and phosphoglycolipids. DNA-DNA relatedness of strain RHGG3T to type strains of the most closely related species (Caulobacter segnis ATCC 21756T, Caulobacter vibrioides DSM 4738 and Caulobacter henricii ATCC 15253T) was 32.4-40.9 %. Based on polyphasic taxonomy analysis (phylogenetic, unique phenotypic traits, chemotaxonomic and DNA-DNA hybridizations), strain RHGG3T represents a novel species of the genus Caulobacter, for which the name Caulobacter flavus sp. nov. is proposed. The type strain is RHGG3T ( = CGMCC 1.15093T = KCTC 42581T = JCM 30763T).

Antibacterial activity of ruthenium(II) polypyridyl complex manipulated by membrane permeability and cell morphology.

This study investigates the antibacterial effects of the ruthenium(II) complex RuBP and the mechanism of RuBP action on bacteria. Results show that RuBP can inhibit the growth of Gram-positive bacteria, such as Staphylococcus aureus and Micrococcus tetragenus. Cellular uptake and laser confocal microscopic studies reveal the efficient uptake of RuBP by M. tetragenus cells. Scanning electron microscopic observations of the morphologies of M. tetragenus and S. aureus treated with RuBP further confirm that direct contact of both bacteria with RuBP can damage the cell membrane and membrane integrity, which may eventually induce growth inhibition and bacterial death. After RuBP treatment, the electrical conductivity of the bacterial suspensions increases. Spectroscopic studies and agarose gel electrophoresis indicate that intact DNA and RNA decrease or disappear in RuBP-treated bacterial cells, thus demonstrating that RuBP performs its antibacterial function by increasing the permeability of cell membranes. This study provides new insights for understanding the antibacterial actions of RuBP and designing metal complex antibiotics for other biomedical applications.

The leucine-responsive regulatory protein SCAB_Lrp modulates thaxtomin biosynthesis, pathogenicity, and morphological development in Streptomyces scabies.

Streptomyces scabies is the best-characterized plant-pathogenic streptomycete, which is a special species among the large genus Streptomyces. The pathogenicity of S. scabies relies on the production of the secondary metabolite thaxtomin A. Little is known about the molecular mechanisms underlying the regulation of thaxtomin biosynthesis in S. scabies beyond the pathway-specific activator TxtR and the cellulose utilization repressor CebR. The leucine-responsive regulatory protein (Lrp) family modulates secondary metabolism in nonpathogenic streptomycetes. However, the regulatory relationship between the Lrp and pathogenic streptomycetes remains unknown. In this study, we demonstrated that SCAB_Lrp (SCAB_77931) from S. scabies significantly affects thaxtomin biosynthesis, pathogenicity, and morphological development. SCAB_Lrp deletion resulted in a dramatic decline in thaxtomin A production and a low-virulence phenotype of S. scabies. An in-depth dissection of the regulatory mechanism of SCAB_Lrp revealed that it positively regulates the transcription of the thaxtomin biosynthetic gene cluster by directly binding to the promoter of the cluster-situated regulator gene txtR. SCAB_Lrp also controls the morphological development of S. scabies by directly activating the transcription of amfC, whiB, and ssgB. SCAB_Lrp directly controls the transcription of its own gene by binding a specific sequence (5'-GGACAGTCGCCGTGCTACG-3'). Moreover, phenylalanine and methionine have been characterized as SCAB_Lrp effectors by strengthening the binding affinity and complex status between SCAB_Lrp and DNA. Our findings characterize a multifunctional regulatory protein, SCAB_Lrp, that controls secondary metabolism, pathogenicity, and sporulation in S. scabies and provide new insights into the complex regulatory network that modulates thaxtomin phytotoxins in pathogenic Streptomyces.

Live bio-nano-sonosensitizer targets malignant tumors in synergistic therapy.

Sonosensitizers that can increase the concentration of reactive oxygen species (ROS) within a tumor microenvironment is a high priority for sonodynamic therapy (SDT). In this study, a functionalized, smart nanosonosensitizer based on Au-RuO2 nanoparticles (NPs) and selenium nanoparticles (Se NPs) that were electrostatically self-assembled onto the surface of Listeria innocua (LI) was used to create Bac@ARS. Au NPs provided the core in which RuO2 was deposited to form Au-RuO2 NPs. Additionally, the underlying properties of the Au NPs and Se NPs were used to optimize the sonosensitivity performance. Compared with pristine RuO2 NPs, Bac@ARS exhibits highly efficient ROS-producing activity. Furthermore, Bac@ARS remodeled the hypoxic tumor microenvironment, enabling overproduction of ROS. Importantly, Bac@ARS exploits the natural tropism of LI to selectively accumulate in tumors, which improved the treatment precision at hypoxic tumor sites after sonodynamic activation. However, the activity of LI was greatly reduced after ultrasound (US) irradiation, ensuring the biosafety of Bac@ARS. Bac@ARS was also used to monitor tumors, in real time, using photoacoustic imaging of the gold-based nanoparticles. Therefore, Bac@ARS is a promising microbial sonosensitizer providing a new platform for the optimization of sonosensitizers for tumor treatment. STATEMENT OF SIGNIFICANCE: A bio-nano-sonosensitizer was designed using a Au nanoparticle (NP) core modified with RuO2 NPs. The Au-RuO2 NPs together with Se-NPs are attached via electrostatic adsorption to a live bacterium Listeria innocua (LI), creating Bac@ARS. The role of the NPs was to optimize the sonosensitivity performance at the target tumor site. Bac@ARS reshaped the tumor microenvironment and overcame tumor hypoxia leading to ROS overproduction. This activated a potent ICD-mediated cellular immunity and anti-tumor activity. Importantly, Bac@ARS exploited the natural tropism of LI to selectively accumulate in tumors, resulting in more precise delivery of the therapeutic effect while exhibiting reduced effects on healthy tissues.

Light-triggered photosynthetic engineered bacteria for enhanced-photodynamic therapy by relieving tumor hypoxic microenvironment.

Background: Singlet oxygen (1O2) has received considerable research attention in photodynamic therapy (PDT) due to its cytotoxic solid features. However, the inherent hypoxic state of the tumor microenvironment (TME) leads to the meager 1O2 quantum yield of inorganic PDT reagents, and their application in vivo remains elusive. Methods: We developed a novel strategy to fabricate active photosynthetic bacteria/photosensitizer/photothermal agent hybrids for photosynthetic tumor oxygenation and PDT and PTT tumor therapy under different laser irradiation sources. Photosynthetic bacteria combined with Ce6 photosensitizer and Au NPs photothermal agent, the obtained Bac@Au-Ce6 effectively targets tumor tissues and further enhances the tumor accumulation of Au-Ce6. Results: The results showed that the Au-Ce6-loaded engineered bacteria (Bac@Au-Ce6) maintained the photosynthetic properties of Syne. After i.v. injection, Bac@Au-Ce6 efficiently aggregates at tumor sites due to the tumor-targeting ability of active Syne. With 660 nm laser irradiation at the tumor site, the photoautotrophic Syne undergoes sustained photosynthetic O2 release and immediately activates O2 to 1O2 via a loaded photosensitizer. PTT was subsequently imparted by 808 laser irradiations to enhance tumor killing further. Conclusions: This work provides a new platform for engineering bacteria-mediated photosynthesis to promote PDT combined with PTT multi-faceted anti-tumor.

L-Arginine-Loaded Gold Nanocages Ameliorate Myocardial Ischemia/Reperfusion Injury by Promoting Nitric Oxide Production and Maintaining Mitochondrial Function.

Cardiovascular disease is the leading cause of death worldwide. Reperfusion therapy is vital to patient survival after a heart attack but can cause myocardial ischemia/reperfusion injury (MI/RI). Nitric oxide (NO) can ameliorate MI/RI and is a key molecule for drug development. However, reactive oxygen species (ROS) can easily oxidize NO to peroxynitrite, which causes secondary cardiomyocyte damage. Herein, L-arginine-loaded selenium-coated gold nanocages (AAS) are designed, synthesized, and modified with PCM (WLSEAGPVVTVRALRGTGSW) to obtain AASP, which targets cardiomyocytes, exhibits increased cellular uptake, and improves photoacoustic imaging in vitro and in vivo. AASP significantly inhibits oxygen glucose deprivation/reoxygenation (OGD/R)-induced H9C2 cell cytotoxicity and apoptosis. Mechanistic investigation revealed that AASP improves mitochondrial membrane potential (MMP), restores ATP synthase activity, blocks ROS generation, and prevents NO oxidation, and NO blocks ROS release by regulating the closing of the mitochondrial permeability transition pore (mPTP). AASP administration in vivo improves myocardial function, inhibits myocardial apoptosis and fibrosis, and ultimately attenuates MI/RI in rats by maintaining mitochondrial function and regulating NO signaling. AASP shows good safety and biocompatibility in vivo. This findings confirm the rational design of AASP, which can provide effective treatment for MI/RI.

Lowered Cd toxicity, uptake and expression of metal transporter genes in maize plant by ACC deaminase-producing bacteria Achromobacter sp.

In this study, an ACC deaminase-producing bacterial strain Achromobacter sp. A1 was isolated from maize rhizosphere soil, characterized and evaluated for the effects on cadmium (Cd) immobilization in solution/rhizosphere, physiological characteristics and the tissue Cd contents in maize and the molecular mechanisms involved by hydroponic and pot experiments. ACC deaminase activity of strain A1 was significantly enhanced by Cd addition and Cd concentration decreased (55.54-63.62%) in solution supplemented with various Cd concentrations. Strain A1 significantly increased the maize dry weights (30.77-105%) and chlorophyll content (7.46-14.46%), decreased MDA content (25.16-36.87%) and ethylene production (20.93-35.86%) in hydroponic experiment. Strain A1 significantly reduced the above-ground tissue Cd uptake by 12.64-33.68% and 42-48% in hydroponic and pot experiments, reduced the DTPA-extractable Cd content and elevated invertase, urease and catalase activity in rhizosphere soils. In addition, the expression levels of Cd transporter genes HMA3 and Nramp5 were significantly reduced in root and shoot after strain A1 inoculation. These results indicate that strain A1 has great potential for application as a novel and environmentally friendly inoculant to immobilize Cd and reduce maize Cd uptake in Cd-contaminated environments, and will improve the understanding of the relative molecular mechanisms underlying the response to strain A1 in maize plant.

A rational design of copper-selenium nanoclusters that cures sepsis by consuming endogenous H2S to trigger photothermal therapy and ROS burst.

The treatment of sepsis caused by bacterial infections is still a huge clinical challenge. As sepsis causes high levels of endogenous H2S in vivo, researchers can design nanomedicines to treat sepsis by in situ sulfurization. Here, we designed and synthesized Cu2O-coated non-metallic core-shell selenium nanoparticles. To cure mice sepsis by ROS burst. Our experimental data displayed that the photothermal effect of Se@Cu9S8 produced by the reaction of Se@Cu2O and endogenous H2S is synergistically antibacterial, and Se@Cu2O has the characteristics of low side effects and high biocompatibility. In summary, our research results verified our design, that copper-selenium nanoclusters may be an efficient strategy to cure sepsis by in situ sulfurization of endogenous H2S, triggering ROS eruptions and photothermal therapy.

Efficient sterilization system combining flavonoids and hyaluronic acid with metal organic frameworks as carrier.

Bacterial infections can cause many human diseases, which are closely related to people's health. Nowadays, antibiotics are mainly used to treat bacterial infections, but the widespread use of antibiotics can also lead to bacterial resistance. Therefore, effective treatment of bacterial infections is an urgent problem to be solved. In this article, a multifunctional therapeutic material with antibacterial properties was designed and synthesized. First, the porous media material ZIF-8 was synthesized, and applied to load hesperidin. When the load is completed, a layer of hyaluronic acid (HA) is uniformly wrapped on surface of the material. Such materials have high stability and high drug-carrying capacity, and can be slowly released in vivo. The HA coated on surface can also promote penetration of active ingredients into cells and give full play to antibacterial ability. Results of in vitro and in vivo antibacterial tests show that synergy between the materials enhances antibacterial activity which is related to dose. The material achieves high-efficiency antibacterial effects by increasing the permeability of cell membranes and destroying the integrity of bacteria. At same time, the material does not show obvious side effects. Therefore, the material seems to be a promising antibacterial agent with good biocompatibility and strong antibacterial activity.

Rhizobium cremeum sp. nov., isolated from sewage and capable of acquisition of heavy metal and aromatic compounds resistance genes.

Two strains of Rhizobia isolated from sewage collected from the Chinese Baijiu distillery were characterized using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strains W15T and W16 were grouped as a separate clade closely related to Rhizobium daejeonense L61T (98.6%). Multilocus sequence analysis (MLSA) with three housekeeping genes (recA, glnII and rpoA) also showed that strains W15T and W16 belonged to the genus Rhizobium. Average nucleotide identity and digital DNA-DNA hybridization values between genome sequences of strain W15T and the closely related species ranged from 77.0% to 87.8% and from 23.9% to 30.9%. The DNA G + C content of strain W15T was 61.6 mol%. Strain W15T contained Q-10 as the major ubiquinone and the dominant fatty acids were summed feature 8 (C 18:1ω7c and/or C 18:1ω6c; 73.1%) and C18:0 (7.6%). The main polar lipids are phosphatidylcholine, phosphatidylmethylethanolamine, phosphatidylethanolamine and phosphatidylglycerol. On the basis of the evidences presented in this study, strains W15T and W16 represents a novel species of the genus Rhizobium, for which the name Rhizobium cremeum sp. nov. is proposed. The type strain is W15T (= CGMCC 1.18731T = KACC 22344T).