Identifying a core protein signature of small extracellular vesicles derived from B-cell precursor acute lymphoblastic leukaemia.

Acute paediatric leukaemia is diagnosed and monitored via bone marrow aspirate assessment of blasts as a measure of minimal residual disease. Liquid biopsies in the form of blood samples could greatly reduce the need for invasive bone marrow aspirations, but there are currently no blood markers that match the sensitivity of bone marrow diagnostics. Circulating extracellular vesicles (EVs) represent candidate biomarkers that may reflect the blast burden in bone marrow, and several studies have reported on the utility of EVs as biomarkers for adult haematological malignancies. Increased levels of EVs have been reported for several haematological malignancies, and we similarly report here elevated EV concentrations in plasma from paediatric BCP-ALL patients. Plasma EVs are very heterogeneous in terms of their cellular origin, thus identifying a cancer selective EV-marker is challenging. Here, we undertook a reductionistic approach to identify protein markers selectively associated to plasma EVs derived from BCP-ALL patients. The EV proteome of primary BCP-ALL cell-derived EVs were compared against EVs from healthy donor B cells and the BCP-ALL cell line REH, and further against EVs isolated from plasma of healthy paediatric donors and paediatric BCP-ALL patients. With this approach, we identified a signature of 6 proteins (CD317, CD38, IGF2BP1, PCNA, CSDE1, and GPR116) that were specifically identified in BCP-ALL derived EVs only and not in healthy control EVs, and that could be exploited as diagnostic biomarkers.

Adaptive cooperative guidance with seeker-less followers: A position coordination-based framework.

This paper addresses the problem of cooperative guidance for multiple flight vehicles, comprising a leader and seeker-less followers. All the flight vehicles are required to hit the target simultaneously at a desired impact time, even though the target information is unavailable to the followers. To achieve this, a fixed-time convergent guidance law is proposed for the leader, incorporating impact time control. We introduce an adaptive cooperative guidance strategy for the seeker-less followers through coordinated position location relative to the leader. The simulation results validate the effectiveness satisfactorily coinciding with the theoretical analysis.

Synthesis and Antioxidant Properties of Psoralen Derivatives.

Five psoralen derivatives were synthesized and the structures of them were characterized by 1 H-NMR, 13 C-NMR, and IR. The antioxidant properties of the compounds were tested by inhibiting the free radical-initiated DNA oxidation and scavenging the radical reaction. The results showed that the effective stoichiometric factors (n) of the compounds V and IV could reach 2.00 and 2.11 in the system of inhibiting the DNA oxidation reaction initiated by 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH). In the inhibition of ⋅OH-oxidation of the DNA system, compounds I~V showed antioxidant properties. The thiobarbituric acid absorbance (TBARS) percentages of compounds IV and V were 76.19 % and 78.84 %. Compounds I~V could also inhibit Cu2+ /GSH-oxidation of DNA, and all compounds exhibited good antioxidant properties except compound II (94.00 %). All the five compounds were able to trap diammonium 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) salt radical (ABTS+ ⋅), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH⋅) and 2,6-di-tert-butyl-alpha-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-p-tolylox radical (galvinoxyl⋅). The ability of compounds I~V to scavenge those free radicals can be measured by the k values. The k values ranged from 0.07 to 0.82 in scavenging ABTS+ ⋅, galvinoxyl, and DPPH radicals, respectively.

Discovery of benzodiazepine derivatives as a new class of covalent inhibitors of SARS-CoV-2 main protease.

The COVID-19 pandemic has caused people immense suffering all over the world. Although the World Health Organization (WHO) has announced the end of the pandemic, the sporadic virus epidemic is still ongoing and may exist permanently. Effective antivirals against SARS-CoV-2 are important to deal with the long-term threat. The main protease (Mpro) is a crucial target for drug development due to its role in the process of virus's replication and transcription. Herein, we report benzodiazepine derivatives as a new class of Mpro inhibitors. Structure-activity relationship (SAR) studies led to the discovery of the most active compound, methyl 10-(2-chloroacetyl)-1-oxo-11-(4-(trifluoromethyl)phenyl)-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]-diazepine-7-carboxylate (11a), which shows an IC50 value of 0.180 ± 0.004 µM. The X-ray crystal structure shows that 11a covalently binds to Mpro. Collectively, we have obtained a new small molecule inhibitor targeting Mpro, which can serve as a lead compound for subsequent drug discovery against SARS-CoV-2.

Generating Topologically Consistent BIM Models of Utility Tunnels from Point Clouds.

The development and utilization of urban underground space is an important way to solve the "great urban disease". As one of the most important types of urban underground foundations, utility tunnels have become increasingly popular in municipal construction. The investigation of utility tunnels is a general task and three-dimensional laser scanning technology has played a significant role in surveying and data acquisition. However, three-dimensional laser scanning technology suffers from noise and occlusion in narrow congested utility tunnel spaces, and the acquired point clouds are imperfect; hence, errors and redundancies are introduced in the extracted geometric elements. The topology of reconstructed BIM objects cannot be ensured. Therefore, in this study, a hierarchical segmentation method for point clouds and a topology reconstruction method for building information model (BIM) objects in utility tunnels are proposed. The point cloud is segmented into facades, planes, and pipelines hierarchically. An improved mean-shift algorithm is proposed to extract wall line features and a local symmetry-based medial axis extraction algorithm is proposed to extract pipelines from point clouds. A topology reconstruction method that searches for the neighbor information of wall and pipeline centerlines and establishes collinear, perpendicular, and intersecting situations is used to reconstruct a topologically consistent 3D model of a utility tunnel. An experiment on the Guangzhou's Nansha District dataset successfully reconstructed 24 BIM wall objects and 12 pipelines within the utility tunnel, verifying the efficiency of the method.

Effects of vegetation restoration on distribution characteristics of heavy metals in soil in Karst plateau area of Guizhou.

In southwest China, vegetation restoration is widely used in karst rocky desertification control projects. This technology can effectively fix the easily lost soil, gradually restore the plant community and improve soil fertility. However, the change law of soil heavy metals in the restoration process remains to be further studied. Therefore, in this work, Guizhou Caohai Nature Reserve as a typical karst area was taken as the research object to investigate the influence of vegetation restoration technology on repairing soil heavy metal pollution. The spatial distribution characteristics of soil heavy metals (chromium, nickel, arsenic, zinc, lead) before and after vegetation restoration in karst area were studied by comparative analysis and linear stepwise regression analysis. The main influencing factors and spatial distribution characteristics of heavy metals in karst area were further discussed. The results showed that: (1) heavy metals in karst soils are affected by surface vegetation, root exudates, microorganisms and leaching. Only heavy metals nickel (Ni) and lead (Pb) showed the tendency of surface enrichment and bottom precipitation enrichment in non-karst soils. Path analysis suggested that non-metallic soil factors such as soil bulk density (BD), total nitrogen (TN) and ammonium nitrogen (NH4 +-N) had direct effect on the content of heavy metals in soil. (2) The proportion of 0.25-2 mm aggregates in the surface soil of vegetation restoration belt was more than 40%, and the proportion of surface soil ≤2 mm aggregates in this increased to 83% and 88%, respectively, which could improve the soil structure and properties effectively. (3) Vegetation restoration effectively restored the nutrient elements such as carbon and nitrogen in the soil, and enhanced the soil material circulation. Furthermore the content of heavy metals in the surface soil higher than that in the 10-20 cm soil layer. Plant absorption, biosorption mechanism of microorganisms, coupling of root exudates, dissolution of soil soluble organic carbon and pH make the contents of heavy metals Cr, Ni and Pb in vegetation restoration belt slightly lower than those in karst soil. At the same time, affected by vegetation coverage, residual heavy metals in soil are further leached by surface runoff. Therefore, the content of heavy metals in soil could reduce combined heavy metal enrichment plants for extraction with remediation. This study elucidates the advantages and remedy mechanism of vegetation restoration in the remediation of heavy metal contaminated soils in Caohai area of Guizhou, and this plant activation and enrichment extraction remediation technology would be popularized and applied in the remediation of heavy metal contaminated soils in other karst areas.

Isolation of a cytolytic subpopulation of extracellular vesicles derived from NK cells containing NKG7 and cytolytic proteins.

NK cells can broadly target and kill malignant cells via release of cytolytic proteins. NK cells also release extracellular vesicles (EVs) that contain cytolytic proteins, previously shown to induce apoptosis of a variety of cancer cells in vitro and in vivo. The EVs released by NK cells are likely very heterogeneous, as vesicles can be released from the plasma membrane or from different intracellular compartments. In this study, we undertook a fractionation scheme to enrich for cytolytic NK-EVs. NK-EVs were harvested from culture medium from the human NK-92 cell line or primary human NK cells grown in serum-free conditions. By combining ultracentrifugation with downstream density-gradient ultracentrifugation or size-exclusion chromatography, distinct EV populations were identified. Density-gradient ultracentrifugation led to separation of three subpopulations of EVs. The different EV isolates were characterized by label-free quantitative mass spectrometry and western blotting, and we found that one subpopulation was primarily enriched for plasma membrane proteins and tetraspanins CD37, CD82, and CD151, and likely represents microvesicles. The other major subpopulation was enriched in intracellularly derived markers with high expression of the endosomal tetraspanin CD63 and markers for intracellular organelles. The intracellularly derived EVs were highly enriched in cytolytic proteins, and possessed high apoptotic activity against HCT-116 colon cancer spheroids. To further enrich for cytolytic EVs, immunoaffinity pulldowns led to the isolation of a subset of EVs containing the cytolytic granule marker NKG7 and the majority of vesicular granzyme B content. We therefore propose that EVs containing cytolytic proteins may primarily be released via cytolytic granules.

An efficient turn-on fluorescence chemosensor system for Zn(II) ions detection and imaging in mitochondria.

Mitochondria-targetable fluorescent chemosensors, Rhodamine-B and rhodamine 6G bearing syringaldehyde based receptors were designed and synthesized for efficient chemosensing of Zinc(II) ions. The probes showed the very selective naked eye color change to pink from colorless upon addition of Zinc(II) ions, further these probes showing turn-on fluorescence enhancement with Zn(II) ions by opening of rhodamine spirolactam. The probes are very sensitive towards Zn(II) ions among other ions. These probes RBS and R6S will be applicable to detect zinc ions upto the low level concentration 0.18 and 0.19 nano molar respectively. The affinity of these sensors RBS and R6S for Zinc (II) ions was found to be in the range of 1.12 × 104 M-1 and 7.28 × 104 M-1 respectively. 1H-nmr titrations of the probes with Zn(II) ions clearly indicating the spiroring opening of the spirolactam. DFT calculations supporting that the perceived photophysical changes of the probes on appendage of the zinc ions. Probes RBS and R6S are useable for selective staining mitochondria. Both of the probes are applicable to reveal labile Zn(II) in live Hela and MCF-7 cells via fluorescence imaging. RBS and R6S are also finding application on quantification of Zinc(II) ions inside mitochondria via fluorescence imaging.

Comparison of characteristics and tumor targeting properties of extracellular vesicles derived from primary NK cells or NK-cell lines stimulated with IL-15 or IL-12/15/18.

NK cell-based therapies have shown promise for hematological cancer forms, but their use against solid tumors is hampered by their poor ability to infiltrate the tumor. NK cells release extracellular vesicles (EVs) containing cytolytic proteins, indicating that NK-cell derived EVs may have therapeutic potential. In this study, we compared the tumor-targeting potential of EVs derived from either primary NK cells or the NK cell lines NK-92 and KHYG-1 cultured in IL-15 alone or in combination with IL-12 and IL-18. Primary NK cells were also stimulated through the activating receptor CD16. Tumor cell apoptosis was measured using a panel of human colon, melanoma, glioblastoma, prostate, breast, and ovarian tumor cell line spheroids. NK cells or NK-92 cells stimulated with IL-12, IL-15, and IL-18 generated EVs with higher efficiency than EVs from resting cells, although similar amounts of EVs were produced under both conditions. Proteomic analysis indicated similar distribution of cytolytic proteins in EVs from primary NK cells and NK-92, but lower levels in KHYG-1 EVs that translated into poor capacity for KHYG-1 EVs at targeting tumor cell lines. Further, we show that CD16-stimulated NK cells release low amounts of EVs devoid of cytolytic proteins. Importantly, EVs from cytokine-stimulated NK cells penetrate into the spheroid core, and tumor spheroid susceptibility to NK-cell derived EVs was linked to differential expression of the NKG2D ligands MICA/B, which was blocked with an anti-NKG2D antibody. We conclude that EVs from activated primary NK cells or NK-92 cells has the best potential to infiltrate and target solid tumors.

Key Metabolite Differences Between Korean Pine (Pinus koraiensis) Seeds With Primary Physiological Dormancy and No-Dormancy.

Pinus Koraiensis seeds have physiological dormancy. Cold stratification releases seed dormancy. The changes in metabolite profiles of dormant seeds and cold stratified seeds during shorter incubation time in a favorable condition for seed germination have been studied. However, a more-long-term detection of the changes in metabolites in dormant seeds can identify the real metabolic pathways responsible for dormancy. Metabolite composition was investigated in embryo and megagametophyte of primary physiological dormant seeds (DS) of P. Koraiensis collected at 0, 1, 2, 4, and 6 weeks of incubation and of non-primary physiological dormant seeds (NDS) sampled at 0 and 1 week of incubation, seed coat rupture stage, and radicle protrusion stage. Embryos contained higher levels of most metabolites than megagametophyte. Strong accumulation of most metabolites in DS occurred at 1 and 4 weeks of incubation. A larger reduction in the relative levels of most phosphorylated sugars and amino acids in NDS was found between 1-week-incubation and seed coat rupture stage. The relative levels of metabolites involved in carbohydrate metabolism, especially the pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle, were higher in the embryos of 4-week-incubated DS, but the relative contents of intermediate metabolites of most amino acid metabolism were lower compared to 1-week-incubated NDS. We suggested that the disturbed carbohydrate metabolism and amino acid metabolism in the embryos of DS after 4 weeks of incubation maybe related to primary dormancy. Our study provides information for a better understanding of the mechanism of seed dormancy.

"Scapegoat" for Offline Consumption: Online Review Response to Social Exclusion.

Previous research has mostly focused on Internet use behaviors, such as usage time of the Internet or social media after individuals experienced offline social exclusion. However, the extant literature has ignored online response behaviors, such as online review responses to social exclusion. To address this gap, drawing on self-protection and self-serving bias, we proposed three hypotheses that examine the effect of offline social exclusion on online reviews, which are verified by two studies using different simulating scenarios with 464 participants. The results show that when individuals are socially excluded offline, regardless of where the exclusion comes from (businesses or peers), they will be more likely to give negative online reviews. In addition, brand awareness moderates the effect of offline social exclusion on online reviews. Specifically, if the brand is less known, compared with social inclusion, offline social exclusion will lead individuals to give more negative online reviews; conversely, for well-known brands, no significant difference exists in the online reviews between social exclusion and inclusion.

Cyclophilin A regulates secretion of tumour-derived extracellular vesicles.

Extracellular Vesicles (EVs) are a heterogenous population of particles that play an important role in cell-cell communication in physiological and pathophysiological situations. In this study we reveal that the peptidyl prolyl isomerase Cyclophilin A (CypA) is enriched in cancer-derived EVs from a range of haematopoietic malignancies. CypA-enriched blood cancer EVs were taken up by normal monocytes independent of EV surface trypsin-sensitive proteins and potently stimulated pro-inflammatory MMP9 and IL-6 secretion. Further characterisation revealed that CypA is intravesicular, however, it is not present in all EVs derived from the haematopoietic cells, instead, it is predominantly located in high density EVs with a range of 1.15-1.18 g/ml. Furthermore, loss of CypA expression in haematological cancer cells attenuates high density EV-induced pro-inflammatory MMP9 and IL-6 secretion from monocytes. Mechanistically, we reveal that homozygous loss or siRNA knockdown of CypA expression significantly reduced the secretion of EVs in the range of 100-200 nm from blood cancer cells under normal and hypoxic conditions. Overall, this work reveals a novel role for CypA in cancer cell EV biogenesis.

Characteristics, Accumulation, and Potential Health Risks of Antimony in Atmospheric Particulate Matter.

Antimony (Sb), a priority pollutant listed by the U.S. Environmental Protection Agency (USEPA), can cause adverse effects on human health, with particular impacts on skin, eyes, gastrointestinal tract, and respiratory system. In this study, a database of Sb concentrations in the global atmosphere was developed through a survey of measurements published in more than 600 articles, which was then used to assess the health risks of Sb exposure based on a USEPA assessment model. Most measurements showed Sb concentrations of less than ∼10 ng m-3, but those at several contaminated sites exhibited Sb concentrations of more than 100 ng m-3. For measurements conducted in urban environments, Sb concentrations in the total suspended particles (TSP) and particles of less than 10 (PM10) or 2.5 µm (PM2.5) were the highest in Asia, followed by Europe, South America, and North America. Sb concentrations were generally higher in winter and fall than during other seasons in TSP and PM10 samples. A significant correlation was observed between Sb and As in TSP and PM2.5 on a global scale. Sb was mainly derived from anthropogenic sources, especially traffic emission, industrial emission, and fossil combustion. Hazard quotients (HQ) of Sb in TSP, PM10, and PM2.5 were higher for children than adults because of their lighter body weight, inferior physical resistance, and higher ingestion probability. The global database for atmospheric Sb concentrations demonstrates a relatively low noncarcinogenic risk in most regions. Long-term monitoring is still required to identify the sources and growth potentials of Sb so that effective control policies can be established.

Notes from the Field: Effectiveness of Prevention and Control Measures for Imported COVID-19 in Guangming District of Shenzhen.

Novel coronavirus disease 2019 (COVID-19) was present in most provinces of China after January 2020. We implemented a surveillance and screening strategy that included early detection of laboratory-confirmed COVID-19 cases and people who were exposed to the disease in Guangming District of Shenzhen. Separate targeted treatment and management strategies were applied to confirmed and suspected cases. From January 23 to March 13, 2020, we found 12 suspected cases, and 11 were confirmed as positive. Although eight of the 11 confirmed cases were family-aggregated, they were all imported cases with common exposure, which did not further cause local community transmission, and no medical staff were infected. After February 14, when the last case was confirmed, there were no newly confirmed cases for 28 consecutive days under the strict outbreak control. The targeted and whole-society involved prevention and control measures prevented the spread of the disease in a very short time and provided a strong guarantee for the orderly recovery of returning to work and social activities.

Status and risks of selenium deficiency in a traditional selenium-deficient area in Northeast China.

In agricultural lands with selenium (Se) deficiency, bioavailability of Se in plants is low. Residents from large-scale agricultural production areas with Se deficiency often suffer from endemic diseases because of consumption of agricultural products lacking in Se. One such area in Northeast China where Keshan disease and Kashin-Beck disease originated, was selected for investigating the geochemistry, influencing factors, and risks of Se in the agroecosystems. Analysis of field samples indicates that the Se deficiency in soil is significantly reduced compared with that of several decades ago, and 62.6% of soils are now Se-sufficient in the southern Songnen Plain. However, Se in crop products remains low due to weak soil-plant transfer, resulting in high risks of Se deficiency related diseases in the rural population of this area. Structural equation modeling, principal component analysis, and other statistical analyses revealed that climate conditions and soil physical and chemical properties are the key factors influencing the spatial distribution of soil Se. Extensive use of agricultural fertilizers may indirectly inhibit the migration of Se from soil to plants. Ensuring sufficient Se contents in agricultural products to meet the minimum daily requirements of residents remains a challenge in Se-deficient areas, especially in the increased agricultural production environment in China.

Distribution patterns and sources of heavy metals in soils from an industry undeveloped city in Southern China.

The accumulations of heavy metals in urban soils are derived from natural parent materials and complex anthropogenic emission sources. This paper investigated metal contamination in urban soils at an industry undeveloped city (Haikou) in southern China, an ideal place to quantitatively assess the contribution of metals from different sources. The concentrations of most heavy metals in the urban soils of Haikou were much lower than their guideline values and that of those from other big cities in China. In contrast, the chemical speciation of metals in this study was similar to those from other cities. The spatial distributions of heavy metals and principal component analysis (PCA) revealed that basaltic parent materials, traffic emissions, and coal combustion were the main factors controlling the distribution of metals in the soils. The Pb isotope signatures of the Haikou soils were greatly different from those of the Beijing and Shanghai soils, but similar to those of the Guangzhou soils, suggesting the common sources of Pb in southern China cities. The results of ternary mixing model of Pb isotopes showed that the contributions of Pb from natural background, coal combustion and traffic emission sources were 5.3-82.4% (mean: 39.7 ± 21.1%), 0-85.7% (mean: 25.5 ± 24.6%), and 1.9-64% (mean: 34.8 ± 22.9%), respectively. This suggests that traffic emission is still the most important anthropogenic source of Pb in Haikou.

Polychlorinated biphenyl quinone induces hepatocytes iron overload through up-regulating hepcidin expression.

Polychlorinated biphenyls (PCBs) are infamous industry by-products or additives, and increasing evidences demonstrated that their exposure is associate with adverse effects on human health. Liver, as the dominate site for xenobiotic metabolism, is apt to be the primary target of PCBs insult. Although PCBs' hepatic toxic effects have been extensively studied, however, the biotransformation of PCBs in liver and the toxicities of associated PCB metabolites are neglected at some extent. Thus, we choose 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ), a surrogate PCB29 metabolite, and evaluated its contribution on hepatotoxicity. In the current study, we discovered PCB29-pQ-induced lipid peroxidation and iron overload both in vivo and in vitro. Further mechanistic research confirmed iron overload is caused by reactive oxygen species (ROS)-driven hepcidin disorder in hepatic cells, and the increase of hepcidin is regulated by the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2).

Levels, sources, isotope signatures, and health risks of mercury in street dust across China.

Spatial distribution and isotope signature of mercury (Hg) in street dusts across China were investigated by collecting dust samples from 14 cities and reviewing previously published data from an additional 46 cities. Potential sources of street dust and the associated health risks to humans were also assessed. The total Hg (THg) concentrations in street dust ranged from 0.020-39.1 mg kg-1 with an average of 0.433 ±â€¯0.185 mg kg-1 in the 60 cities. Street dust samples collected from 14 cities were characterized by slightly negative δ202Hg (-0.61 ±â€¯0.92‰) and near-zero Δ199Hg (-0.03 ±â€¯0.08‰) values, and coal combustion and industrial activities were estimated to be the major sources of Hg in street dust. The estimated average probable daily intake (PDI) of THg from street dust exposure for adults and children (1.36E-03 and 1.27E-02 µg d-1 kg-1, respectively) were comparable to their respective exposures via rice consumption in China. Children being exposed to THg in dust is a major concern in mercury mining areas (e.g., Wangshan and Xunyang), and may also be a concern in cities with major coal-based industries and nonferrous metal smelting. Results from this study suggest that exposure to street dust is not a primary MeHg exposure pathway in China.

Georhizobium profundi gen. nov., sp. nov., a piezotolerant bacterium isolated from a deep-sea sediment sample of the New Britain Trench.

A novel alphaproteobacterium, strain WS11T, was isolated from a deep-sea sediment sample collected from the New Britain Trench. The full-length 16S rRNA gene of strain WS11T had the highest sequence similarity of 97.6 % to Rhizobium subbaraonis JC85T, followed by Mycoplana ramosa DSM 7292T (96.9 %) and Rhizobium azooxidifex Po 20/26T (96.8 %). Phylogenetic analysis of concatenated 16S rRNA, atpD and recA gene sequences showed that strain WS11T was deeply separated from the species within the family Rhizobiaceae. Phylogenomic analysis based on the whole-genome protein sequences showed that strain WS11T formed an independent monophyletic branch in the family Rhizobiaceae, paralleled with the species in the families Brucellaceae and Phyllobacteriaceae within the order Rhizobiales. Cells were Gram-stain-negative, oxidase- and catalase-positive, and aerobic short rods (1.5-2.4×0.9-1.0 µm). Growth was observed at salinities ranging from 0 to 5% (optimum, 1 %), from pH 6.5 to 9 (optimum, pH 7) and at temperatures between 20 and 30 °C (optimum, 28 °C). Strain WS11T was piezotolerant, growing optimally at 0.1 MPa (range 0.1-70 MPa). The main fatty acid was summed feature 8 (C18 : 1 ω7c/C18  : 1 ω 6c). The sole respiratory quinone was ubiquinone-10 (Q-10). The predominant polar lipids were phosphatidylcholine, two unidentified aminophospholipids and an unidentified phospholipid. The genome size was about 4.36 Mbp and the G+C content was 62.3 mol%. The combined genotypic and phenotypic data show that strain WS11T represents a novel species of a novel genus in the family Rhizobiaceae, for which the name Georhizobium profundi gen. nov., sp. nov. is proposed (type strain WS11T=MCCC 1K03498T=KCTC 62439T).

Polychlorinated biphenyl quinone promotes macrophage polarization to CD163+ cells through Nrf2 signaling pathway.

Polychlorinated biphenyls (PCBs) are notorious environmental pollutants. For their hydrophobic and lipophilic capability, they are wildly spread to environment to threat human health thus attracts more attention. In this study, we observed increasing numbers of CD163 positive (CD163+) macrophages in aortic valve of ApoE-/- mice after 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ) treatment, the metabolite of polychlorinated biphenyl. In addition, in vitro studies identified that PCB29-pQ exposure significantly provoked the shifting of RAW264.7 macrophages and bone marrow derived monocytes (BMDMs) to CD163+ macrophages. Upon PCB29-pQ administration, CD163 and CD206 levels were enhanced in RAW264.7 cells as well as in BMDMs. However, the concentration of iron and total cholesterol (TC) were reduced due to the boosting of ferroportin (Fpn) and ATP binding cassette transporter, subfamily A, member 1 (ABCA1) which are efflux transporters of iron and cholesterol individually. Further investigation on mechanism indicated that PCB29-pQ exposure induced reactive oxygen species (ROS), which may result in activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a protein responsible for macrophage polarization. After that, we blocked Nrf2 through Nrf2 shRNA and ROS scavenger NAC, which significantly reversed the shifting of macrophage to CD163+ sub-population. These results confirmed the importance of Nrf2 in inducing macrophage polarization. In short, our study uncovered that PCB29-pQ could promote macrophage/monocyte polarization to CD163+ macrophage which would be a potential incentive to accelerate atherosclerosis through Nrf2 signaling pathway.