116 research outputs found

    Electrical and magnetic properties of antiferromagnetic semiconductor MnSi2N4 monolayer

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    Two-dimensional antiferromagnetic semiconductors have triggered significant attention due to their unique physical properties and broad application. Based on first-principles calculations, a novel two-dimensional (2D) antiferromagnetic material MnSi2N4 monolayer is predicted. The calculation results show that the two-dimensional MnSi2N4 prefers an antiferromagnetic state with a small band gap of 0.26 eV. MnSi2N4 has strong antiferromagnetic coupling which can be effectively tuned under strain. Interestingly, the MnSi2N4 monolayer exhibits a half-metallic ferromagnetic properties under an external magnetic field, in which the spin-up electronic state displays a metallic property, while the spin-down electronic state exhibits a semiconducting characteristic. Therefore, 100% spin polarization can be achieved. Two-dimensional MnSi2N4 monolayer has potential application in the field of high-density information storage and spintronic devices

    Cryo-EM structures of lipopolysaccharide transporter LptB2FGC in lipopolysaccharide or AMP-PNP-bound states reveal its transport mechanism

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    Lipopolysaccharides (LPS) of Gram-negative bacteria are critical for the defence against cytotoxic substances and must be transported from the inner membrane (IM) to the outer membrane (OM) through a bridge formed by seven membrane proteins (LptBFGCADE). The IM component LptB2FG powers the process through a yet unclarified mechanism. Here we report three high-resolution cryo-EM structures of LptB2FG alone and complexed with LptC (LptB2FGC), trapped in either the LPS- or AMP-PNP-bound state. The structures reveal conformational changes between these states and substrate binding with or without LptC. We identify two functional transmembrane arginine-containing loops interacting with the bound AMP-PNP and elucidate allosteric communications between the domains. AMP-PNP binding induces an inward rotation and shift of the transmembrane helices of LptFG and LptC to tighten the cavity, with the closure of two lateral gates, to eventually expel LPS into the bridge. Functional assays reveal the functionality of the LptF and LptG periplasmic domains. Our findings shed light on the LPS transport mechanism

    Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate

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    This study investigated the effects of pregnane X receptor (PXR/NR1I2) and CYP2B6 genetic variants on sodium ferulate (SF)-mediated induction of bupropion hydroxylation. The pharmacokinetics of bupropion and hydroxybupropion were evaluated after an oral dose of bupropion (150 mg) administered with and without SF pretreatment for 14 days in 33 healthy subjects. The area under the time-concentration curve (AUC) ratio of AUC_hyd (AUC(0-∞) of hydroxybupropion)/AUC_bup (AUC(0-∞) of bupropion) represents the CYP2B6 hydroxylation activity, which was significantly lower in CYP2B6*6 carriers (NR1I2 TGT noncarriers or carriers) than in noncarriers in both the basal and SF-induced states (p-value<0.05). AUC ratio and AUC_hyd of NR1I2 -24113AA variant were markedly lower than GA and GG genotypes (7.5±2.1 versus 14.5±3.3 and 20.6±1.1, and 8873±1431 versus 14,504±2218 and 17,586±1046) in the induced states. However, -24020(-)/(-) variant didn't show significant difference in the induction of CYP2B6 hydroxylation activity by SF compared with other -24020[GAGAAG]/(-) genotypes. NR1I2 TGT haplotype (-25385T+g.7635G+g.8055T) carriers exhibited a significantly decreased AUC ratio, compared with TGT noncarriers, in the basal states (7.6±1.0 versus 9.7±1.0), while this result wasn't observed in CYP2B6*6 noncarriers. Moreover, individuals with complete mutation-type [CYP2B6*6/*6+NR1I2 TGT+ -24113AA+ -24020 (-)/(-)] showed even lower percent difference of AUC ratio (8.7±1.2 versus 39.5±8.2) than those with complete wild-type. In conclusion, it is suggested that NR1I2 variants decrease the bupropion hydroxylation induced by SF treatment, particularly in CYP2B6*6 carriers

    Microglia-Specific Promoter Activities of HEXB Gene

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    Adeno-associated virus (AAV)-mediated genetic targeting of microglia remains a challenge. Overcoming this hurdle is essential for gene editing in the central nervous system (CNS). Here, we characterized the minimal/native promoter of the HEXB gene, which is known to be specifically and stably expressed in the microglia during homeostatic and pathological conditions. Dual reporter and serial deletion assays identified the critical role of the natural 5’ untranslated region (−97 bp related to the first ATG) in driving transcriptional activity of the mouse Hexb gene. The native promoter region of mouse, human, and monkey HEXB are located at −135, −134, and −170 bp to the first ATG, respectively. These promoters were highly active and specific in microglia with strong cross-species transcriptional activities, but did not exhibit activity in primary astrocytes. In addition, we identified a 135 bp promoter of CD68 gene that was highly active in microglia but not in astrocytes. Considering that HEXB is specifically expressed in microglia, these data suggest that the newly characterized microglia-specific HEXB minimal/native promoter can be an ideal candidate for microglia-targeting AAV gene therapy in the CNS

    MoNuSAC2020:A Multi-Organ Nuclei Segmentation and Classification Challenge

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    Detecting various types of cells in and around the tumor matrix holds a special significance in characterizing the tumor micro-environment for cancer prognostication and research. Automating the tasks of detecting, segmenting, and classifying nuclei can free up the pathologists' time for higher value tasks and reduce errors due to fatigue and subjectivity. To encourage the computer vision research community to develop and test algorithms for these tasks, we prepared a large and diverse dataset of nucleus boundary annotations and class labels. The dataset has over 46,000 nuclei from 37 hospitals, 71 patients, four organs, and four nucleus types. We also organized a challenge around this dataset as a satellite event at the International Symposium on Biomedical Imaging (ISBI) in April 2020. The challenge saw a wide participation from across the world, and the top methods were able to match inter-human concordance for the challenge metric. In this paper, we summarize the dataset and the key findings of the challenge, including the commonalities and differences between the methods developed by various participants. We have released the MoNuSAC2020 dataset to the public

    Sustainable Chemoenzymatic Cascade Transformation of Corncob to Furfuryl Alcohol with Rice Husk-Based Heterogeneous Catalyst UST-Sn-RH

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    Valorization of the abundant renewable lignocellulose through an efficient chemoenzymatic strategy to produce the furan-based platform compounds has raised great interest in recent years. In this work, a newly prepared sulfonated tin-loaded rice husk-based heterogeneous chemocatalyst UST-Sn-RH was utilized to transform corncob (75.0 g/L) into furfural (72.1 mM) at 170 °C for 30 min in an aqueous system. To upgrade furfural into furfuryl alcohol, whole cells of recombinant E. coli KPADH harboring alcohol dehydrogenase were employed to transform corncob-derived furfural into furfuryl alcohol at 30 °C and pH 7.5. In the established chemoenzymatic cascade process, corncob was efficiently transformed to furfuryl alcohol with a productivity of 0.304 g furfuryl alcohol/(g xylan in corncob). In general, biomass could be efficiently valorized into valuable furan-based chemicals in this tandem reaction with the chemocatalyst (bio-based UST-Sn-RH) and the biocatalyst (KPADH cell) in an aqueous system, which has potential application

    Diagnosis of Territorial Space Ecological Restoration Areas in Urban Agglomeration: A Case Study of Guangdong-Hong Kong-Macao Greater Bay Area

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    Territorial space ecological restoration has become a significant strategy for the construction of China's ecological civilization. It is also an important strategic task related to national ecological security and human well-being. The continuous expansion of space in urban agglomerations and the high-intensity development of cities have exacerbated the fragmentation of natural landscapes. The ecological security of urban agglomerations and the ecological restoration of territorial spaces have become key issues of common concern to the government and scholars. Currently, the research on ecological restoration of territorial space mostly focuses on the identification of ecological restoration areas based on the key components of ecological security patterns and rarely discusses the coordinated protection and restoration of urban agglomerations by combining the ecological security patterns with human activities. It is particularly necessary to identify the ecological restoration areas and build a technical paradigm for ecological protection and territorial space restoration that can provide a basic support for the ecological integration, construction, and sustainable development of urban agglomerations. Based on ecological network construction and human disturbance assessment, this study diagnoses the territorial space ecological restoration areas of Guangdong-Hong Kong-Macao Greater Bay Area and proposes ecological protection and restoration strategies for the territorial space ecological source restoration area, ecological corridor restoration area, and stepping stone restoration area. The results showed that: (1) Human activities in the Guangdong-Hong Kong-Macao Greater Bay Area had high interference intensities and a wide impact on the ecological environment; areas with high and relatively high interference accounted for 48.65% of the total area, mainly concentrated in the central part of the Greater Bay Area. (2) The ecological network of Guangdong-Hong Kong-Macao Greater Bay Area presented a relatively stable characteristic pattern of "2 breadth lines and 4 length lines". The 2-breadth lines included the continuous mountains in the north and the ecological protection belt of the southern coastal waters. The 4-length lines included the eastern and western land corridors and the central water corridors. (3) The ecological source restoration area of the Guangdong-Hong Kong-Macao Greater Bay Area was 4,687.42 km2, the ecological corridor restoration length was 1,362.71 km, and the stepping stone restoration area was 833.82 km2, mainly distributed in Zhaoqing, Huizhou, and Jiangmen. To limit human disturbance and restore ecological functions, strategies for territorial space ecological restoration were proposed based on the ecological network function and structural integrity; (4) It is urgent for government departments to overcome the concept of regionalism and build a consensus on the co-disposal of ecological restoration in the territorial space. The construction of cross-domain collaborative governance institutions will efficiently promote the ecological restoration of cross-regional territorial spaces. Considering both human and ecological systems, this study discussed the ecological restoration schema in key areas of ecological networks, coastal ecological restoration areas, and trans-regional ecological restoration areas. The method for urban agglomeration territorial space ecological restoration was formed, including "ecological network pattern-human activity disturbance-restoration area diagnosis-restoration strategy," which will provide a framework for promoting the territorial space ecological protection and restoration in the Guangdong-Hong Kong-Macao Greater Bay Area

    Fast acquisition method using modified PCA with a sparse factor for burst DS spread-spectrum transmission

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    To improve the acquisition speed and inbound capacity of the ground station in a burst direct-sequence (DS) spread-spectrum transmission system, an acquisition method based on a modified parallel code-phase acquisition (PCA) scheme is proposed. By taking advantage of the sparsity of the acquisition result with PCA in the time domain, we introduce the sparse factor to handle the signals via sparsification and apply the sparse recovery algorithm to search and estimate the acquisition result. The computational complexity, mean acquisition time, and relationship between the inbound capacity and acquisition performance are provided. We theoretically analyse the effect of the sparse factor on the acquisition performance. The estimation errors verify our analysis, and simulations show that the acquisition time of our proposed method outperforms that of advanced PCA by 1.2–4.0 times; additionally, the inbound capacity increases by 6.2–36.7%

    Enhancement of doxorubicin production in Streptomyces peucetius by genetic engineering and process optimization

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    Abstract Doxorubicin is an important class of anthracycline antitumor antibiotics produced by Streptomyces peucetius. The doxorubicin fermentation yield of the wild-type strain was very low, so it could not be produced directly by fermentation at an industrial scale due to the high cost. In the present study, S. peucetius SIPI-7-14 was obtained from SIPI-14 through several rounds of doxorubicin resistance screening. Then, the ketoreductase gene dnrU was knocked out to reduce (13S)-13-dihydrodaunorubicin production, and the resistance gene drrC was overexpressed to further enhance resistance to doxorubicin. The resulting engineered strain S. peucetius △U1/drrC produced 1128 mg/L doxorubicin, a 102.1% increase compared to that of SIPI-14. Then, fermentation medium was optimized using the response surface method. In the optimized fermentation medium, the yield of doxorubicin was increased to 1406 mg/L in shake flask on the 7th day. Furthermore, batch culture was carried out in a 10 L fermenter, and the concentration of doxorubicin reached 1461 mg/L after 7 days of culture, which was the highest yield reported to date, indicating the potential for industrial production of doxorubicin by fermentation
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