68 research outputs found

    Transformation of \u3ci\u3eFusarium verticillioides\u3c/i\u3e with a polyketide gene cluster isolated from a fungal endophyte activates the biosynthesis of fusaric acid

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    A large number of bioactive natural products have been isolated from plant endophytic fungi. However, molecular mechanisms for the biosynthesis of these metabolites have lagged behind because genetic and biochemical studies are difficult to perform within many of the endophytes. In this work, we describe our attempt to express a putative mycoepoxydiene (MED) biosynthetic gene cluster in Fusarium verticillioides, which has a well-developed genetic system for the study fungal polyketide biosynthesis. MED was isolated from Phomopsis sp. A123, a fungal endophyte of the mangrove plant, Kandelia candel. It has several unusual structural features and interesting biological activities. Integration of this Phomopsis gene cluster into the F. verticillioides genome led to the biosynthesis of multiple metabolites. The most highly activated metabolite was isolated and its structure was shown by 1D- and 2D-NMR to be fusaric acid, which is a mycotoxin in Fusarium species and is implicated in fungal pathogenesis. Although fusaric acid was isolated more than 70 years ago, its biosynthetic mechanism remains unclear. These transformants produced 30–35 mg fusaric acid per 100 ml culture. The high level production of fusaric acid will greatly facilitate the genetic and biochemical study of its biosynthetic mechanism. Although we have not detected MED or its analogs from the heterologous host, this work represents the first attempt to express a fungal endophytic gene cluster in a Fusarium species

    Effects of synthetic colloids on oxidative stress and inflammatory response in hemorrhagic shock: comparison of hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, and succinylated gelatin

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    INTRODUCTION: This study compared the effects of hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, and succinylated gelatin on oxidative stress and the inflammatory response in a rodent hemorrhagic shock model. METHODS: Sodium pentobarbital-anesthetized adult male Wistar rats (200 g to 220 g) were subjected to a severe volume-controlled hemorrhage using arterial blood withdrawal (30 mL/kg to 33 mL/kg) and resuscitated with a colloid solution at the same volume as blood withdrawal (hydroxyethyl starch 130/0.4, hydroxyethyl starch 200/0.5, or succinylated gelatin). Arterial blood gas parameters were monitored. Malondialdehyde (MDA) content and myeloperoxidase (MPO) activity in the liver, lungs, intestine, and brain were measured two hours after resuscitation. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 in the intestine were also measured. RESULTS: Infusions of hydroxyethyl starch 130/0.4, but not hydroxyethyl starch 200/0.5 or succinylated gelatin, significantly reduced MDA levels and MPO activity in the liver, intestine, lungs and brain, and it also inhibited the production of TNF-α in the intestine two hours after resuscitation. However, no significant difference between hydroxyethyl starch 200/0.5 and succinylated gelatin was observed. CONCLUSIONS: Hydroxyethyl starch 130/0.4, but not hydroxyethyl starch 200/0.5 or succinylated gelatin, treatment after hemorrhagic shock ameliorated oxidative stress and the inflammatory response in this rat model. No significant differences were observed after hydroxyethyl starch 200/0.5 or succinylated gelatin administration at doses of approximately 33 mL/kg

    Mutations in m6A consensus motifs are suppressed in the m6A modified genes in human cancer cells.

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    N6-methyladenosine (m6A) is the most prevalent type of RNA modification. METTL3 in the methyltransferase complex is the core enzyme responsible for methylation. METTL3 selectively catalyzes the adenosines centered in the RRAC motif. Functional studies established that m6A could enhance the translation efficiency (TE) of modified genes by recruiting reader protein YTHDF1 and other initiation factors. We downloaded the m6A peaks in HeLa cells from a previous study and defined the m6A modified genes and sites. Ancestral mutations in the genic region fixed in the HeLa cell samples were defined using their mRNA-Seq data and the alignment between human and mouse genomes. Furthermore, in the small interfering (si)-METTL3 sample, the calculated TE foldchange of all genes was compared to that in the negative control. The TE of m6A genes was globally down-regulated in si-METTL3 versus control compared to the non-m6A genes. In m6A modified genes, RRAC motif mutations were suppressed compared to mutations in non-motif regions or non-m6A genes. Among the m6A genes, a fraction RRAC motif mutations negatively correlated with the TE foldchange (si-METTL3 versus control). The TE of m6A modified genes was enhanced in HeLa cells. RRAC motif mutations could potentially prevent methylation of adenosines and consequently abolish the enhanced translation. Such mutations in the RRAC motif might be deleterious. Accordingly, we observed lower fractions of mutations in RRAC motifs than in other regions. This prevention of mutations in the RRAC motif could be a strategy adopted by cancer cells to maintain the elevated translation of particular genes

    Rejuvenation behavior of Cu–Zr metallic glass under different holding times during deep cryogenic cycling treatment: Experiments and simulation

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    The rejuvenation behavior of Cu–Zr binary metallic glasses with different holding times in both ambient and cryogenic temperatures during deep cryogenic cycling treatment were investigated in details. The degrees of rejuvenation, the structure and properties were investigated by both experiments and simulation. It is found that the holding times can significantly affect the rejuvenation behavior. The samples with different holding times can be either aged or rejuvenated, that is, the shorter holding times could effectively rejuvenate the samples, while the longer holding times aged the samples. Such phenomenon can be observed from both experimental and simulation results. It is also found that the fraction of liquid-like structure increases while solid-like structure decreases in the short-range ordered structures for those rejuvenated samples, leading to a more heterogeneous structure. Such changes in local atomic structure contributes to the improvement in the mechanical properties, which is related to delocalization of the shearing events and the formation of more shear-transformation zones. The present study contributes to the understanding of the correlation between the treatment parameters during deep cryogenic cycling treatment and the rejuvenation behavior, as well as the structural evolution

    A Performance–Consumption Balanced Scheme of Multi-Hop Quantum Networks for Teleportation

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    Teleportation is an important protocol in quantum communication. Realizing teleportation between arbitrary nodes in multi-hop quantum networks is of great value. Most of the existing multi-hop quantum networks are based on Bell states or Greeberger–Horne–Zeilinger (GHZ) states. Bell state is more susceptible to noise than GHZ states after purification, but generating a GHZ state consumes more basic states. In this paper, a new quantum multi-hop network scheme is proposed to improve the interference immunity of the network and avoid large consumption at the same time. Teleportation is realized in a network based on entanglement swapping, fusion, and purification. To ensure the robustness of the system, we also design the purification algorithm. The simulation results show the successful establishment of entanglement with high fidelity. Cirq is used to verify the network on the Noisy Intermediate-Scale Quantum (NISQ) platform. The robustness of the fusion scheme is better than the Bell states scheme, especially with the increasing number of nodes. This paper provides a solution to balance the performance and consumption in a multi-hop quantum network

    Development and Preliminary Practice of Resilience-oriented Structured Treatment and Educational Program for Adolescents with Type 1 Diabetes

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    Background The poor control of type 1 diabetes in Chinese adolescents has brought a heavy burden to families and society. Diabetes education in China is mainly aimed at patients with type 2 diabetes, and there is a lack of self-management support programs for adolescents with type 1 diabetes.Objective To develop a resilience-oriented structured treatment and educational program for type 1 diabetic adolescents, and to verify its applicability and feasibility among Chinese adolescents with type 1 diabetes.Methods This study was conducted during January to May 2020. Guided by the diabetes resilience model, the analysis of needs of adolescents with type 1 diabetes through literature analysis and interviews, and references obtained from the available structured educational model for type 1 diabetes, a draft resilience-oriented structured treatment and educational program for adolescents with type 1 diabetes was developed, then was revised and improved according to the results of the expert consultation. After wards, potential participants were recruited by posters posted in the outpatient department and telephone to attend a trial test conducted in the First Affiliated Hospital with Nanjing Medical University to evaluate the feasibility of the program from three aspects: recruitment response rate, authenticity and acceptability.Results The final program covers 43 teaching objectives in 3 fields, including 12 in the field of perceptions, 14 in the behavioral field and 17 in the emotional field. The program adopts group teaching method, with 5-8 patients, 1 doctor and 1 nurse in each group. There were 6 classes in a course cycle. A total of 8 adolescents were recruited in the feasibility analysis, of whom 6 adolescents completed all courses. Patients said that the course content was close to life and the class atmosphere was relaxed, and their levels of self-management ability, acceptance of diabetes and emotion regulation ability were all improved after learning the program.Conclusion The resilience-oriented structured treatment and educational program has systematic contents, standardized implementation process and high feasibility, which is worthy of further clinical verification

    Structure-antibacterial relationship of nigericin derivatives

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    Two new polyether antibiotics 3, 5 together with three known ones 1, 2, 4 were isolated from Streptomyces hygroscopicus XM201. Based on the unambiguous NMR data assignments, their structures were determined to be 30-acetyl nigericin (1), 1-O-methyl-30-acetyl nigericin (2), 1,29-O-dimethyl-30-acetyl nigericin (3), nigericin (4), and 29-O-methyl abierixin (5), respectively. The antibacterial activities of the nigericin derivatives 1-4 were studied. Compounds 1 and 4 showed strong activities against Staphylococcus aureus ATCC25923 and Bacillus cereus 1126 with MIC of 0.25 mu g/mL and 0.125 mu g/mL, respectively. No inhibitory activities were observed against Escherichia coli CMCC44103 at a concentration of 25 mu g/mL. Only 1 and 4 showed distinguished effects on the protoplast regeneration clones of B. cereus 1126 and E. coli CMCC44103 at a concentration of 1 mu g/mL.National Natural Science Foundation of China [30500632]; Chinese Ministry of Education [306010]; 863 Project [2006AA10A202

    Thermal-pressure treatment for tuning the atomic structure of metallic glass Cu-Zr

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    Both thermal and pressure treatments are effective to obtain rejuvenated metallic glass (MG) with high energy state and densely packed structure. In this study, we studied the changes of potential energy and atomic volume under various cooling rate and pressure during quenching stage for Cu-Zr MGs by atomic structure analysis. It is found that: (1) Increasing pressure leads to monotonous increasing potential energy but decreasing and then increasing atomic volume; (2) The potential energy becomes higher, and the densest atomic structure is obtained at a higher pressure with more Cu content; (3) Higher energy state obtained by increasing pressure is corresponding to more full icosahedron and 1551 bond type. This work provides a profound understanding of rejuvenated MG with high energy and unique atomic structure by thermal-pressure treatments.This work was supported by the Xuzhou Key Research & Development Program(KC17015), and the China Postdoctoral Science Foundation (2018T110569 and 2018M630623
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