214 results on '"Guo ZK"'
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2. Fatty Acids Inhibit Intramyocellular Triglyceride Synthesis and Turnover Acutely in High Fat-fed Obese Rats
- Author
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Guo, ZK., primary and Zhou, L., additional
- Published
- 2006
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3. De novo lipogenesis in adipose tissue of lean and obese women: application of deuterated water and isotope ratio mass spectrometry
- Author
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Guo, ZK, primary, Cella, LK, additional, Baum, C, additional, Ravussin, E, additional, and Schoeller, DA, additional
- Published
- 2000
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4. Maduraflavacins A-E, Unusual Phenyl Polyene Metabolites Produced by a Rare Marine-Derived Actinomadura sp.
- Author
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Zou Y, Shi J, Sun JL, Li LY, Yan ZY, Guo ZK, and Jiao RH
- Abstract
Phenyl polyenes comprise a small family of bacterial natural products with broad and potent bioactivities, primarily found in actinobacteria. Here we report the discovery of five new phenyl polyene metabolites, maduraflavacins A-E ( 1 - 5 ), from a rare, marine-derived actinobacteria strain Actinomadura glauciflava NA03286. The structures of these natural products were determined by NMR spectroscopy, HRESIMS, LC-MS/MS, and chemical derivatization. All of these new maduraflavacins feature methyl substitutions at the polyene side chain, and maduraflavacins A-C ( 1 - 3 ) possessed a 1- N -β-d-glucosamine-(3 → 1)- O -β-d-glucopyranosyl-(3 → 1)- O -β-d-glucopyranosyl-(6 → 1)- O -β-d-glucopyranoside tetrasaccharide moiety via an amido linkage with a phenyl polyene skeleton. Compounds 1 and 2 showed weak antibacterial activities against the Gram-positive bacteria Staphylococcus aureus Sau 16339 and Micrococcus luteus , respectively.
- Published
- 2024
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5. Physical and chemical characterization of chitin and chitosan extracted under different treatments from black soldier fly.
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Yuan BQ, Yu TH, Chen SC, Zhang ZQ, Guo ZK, Huang GX, Xiao JH, and Huang DW
- Abstract
The shell of Hermetia illucens L. contains considerable amounts of chitin, which has various biological activities. So far, few studies have focused on chitin of Hermetia illucens L. as a source of chitosan and oligosaccharides. There is great potential for utilizing Hermetia illucens L. chitin to produce chitosan films in biomaterials. We studied different extraction conditions for chitin and extracted it from black soldier fly (BSF) (Hermetia illucens L.). Three processing steps were adopted: (1) demineralization, (2) deproteinization, and (3) decolorization. The chemical components (moisture, ash, protein, fat, residual protein, and residual mineral contents) and physicochemical characteristics of the chitin and chitosan extracted under these three conditions were determined. In addition, Fourier transform infrared spectroscopy and X-ray diffraction were used to analyze the extracted chitin and commercial samples, and the results showed that demineralization-deproteinization-decolorization treatments could achieve the highest chitin yield (7.18 ± 0.11 %), chitosan yield (64.22 ± 0.79 %), and the best purity (residual protein 0.56 ± 0.01 % and residual ash 0.58 ± 0.04 %), making it the best treatment method. Using this method, the residues produced from farmed BSF can be recycled and used as a new source of chitin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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6. Isolation and biological activity of six new polyketide and terpenoid derivatives from Neopestalotiopsis Clavispora AL01.
- Author
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Abulaizi A, Xiong ZJ, Wang ZR, Yang Y, Zhang SQ, Yuan JZ, Chen BT, Ge HM, and Guo ZK
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- Molecular Structure, Plant Leaves chemistry, Nicotiana, Microbial Sensitivity Tests, China, Biological Products pharmacology, Biological Products isolation & purification, Biological Products chemistry, Methicillin-Resistant Staphylococcus aureus drug effects, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents isolation & purification, Anti-Bacterial Agents chemistry, Polyketides pharmacology, Polyketides isolation & purification, Polyketides chemistry, Terpenes pharmacology, Terpenes isolation & purification
- Abstract
A fungus strain, Neopestalotiopsis clavispora AL01, was isolated from the leaf spot of the plant Phoenix dactylifera. Further chemical investigation of the fermentation extract of this strain afforded six new secondary metabolites (1-6), along with 11 known compounds (7-17) which included a new natural compound (7). Their structures were determined by extensive spectroscopic analysis including one-and two-dimensional (1D and 2D) NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), and ECD and NMR calculations. All compounds were evaluated for their phytotoxic activities. Among them, compounds 10, 12 and 13 exhibited phytotoxic activities against Nicotiana tabacum. Compound 3 exhibited weak antibacterial activity against methicillin-resistant Staphylococcus aureus, Micrococcus luteus and Vibrio harveyi. Taken collectively, these findings establish a solid research foundation for future investigations on bioactive natural products derived from phytopathogenic fungi., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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7. Haploidentical Hematopoietic Stem Cell Transplantation for Paediatric Patients with X-linked Lymphoproliferative Syndrome.
- Author
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Jiang F, Sun Y, Liu ZY, Fan SF, Xiao J, Chen J, Liu HY, Wu NH, and Guo ZK
- Abstract
The aim of this study was to investigate the prognostic factors of haploid hematopoietic stem cell transplantation in the treatment of X-linked lymphoproliferative syndrome. Seven children with X-linked lymphoproliferative syndrome diagnosed by XIAP gene analysis were enrolled. The conditioning regimens were tolerated in all seven patients, and the median time of neutrophil engraftment was 10 days (8-13 days), and that of platelet engraftment was 21 days (14-24 days). STR-PCR analysis on the peripheral blood cells showed complete donor origins. Four cases developed Grade I acute graft versus host disease (aGVHD), one developed Grade III aGVHD (intestinal tract), and two cases had limited chronic GVHD. Four cases had cytomegalovirus (CMV) reactivation, and two cases had Epstein-Barr virus (EBV) reactivation. One case was diagnosed as pneumocystosis, and thrombotic microangiopathy (TMA) occurred in three cases. During the follow-up period (median time of 42 months), one patient died of TMA and six patients survived. Statistical analysis showed that the status of disease remission and the positive result of virus in blood before transplantation were independent prognostic factors. Haplo-HSCT might be a curative option for children with refractory X-linked lymphoproliferative syndrome. Low-intensity conditioning regimens may reduce transplant-related mortality and improve overall survival., Competing Interests: Competing interests: The authors declare no conflict of Interest.
- Published
- 2024
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8. Green preparation of CaO-based CO 2 adsorbent by calcium-induced hydrogenation of shell wastes at room/moderate temperature.
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Hao YY, Xiao MX, Mao GC, Wang JP, Guo ZK, Dong BX, and Teng YL
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- Hydrogenation, Temperature, Animal Shells chemistry, Egg Shell chemistry, Adsorption, Green Chemistry Technology methods, Carbon Dioxide analysis, Carbon Dioxide chemistry, Refuse Disposal methods
- Abstract
Capturing CO
2 using clamshell/eggshell-derived CaO adsorbent can not only reduce carbon emissions but also alleviate the impact of trash on the environment. However, organic acid was usually used, high-temperature calcination was often performed, and CO2 was inevitably released during preparing CaO adsorbents from shell wastes. In this work, CaO-based CO2 adsorbent was greenly prepared by calcium-induced hydrogenation of clamshell and eggshell wastes in one pot at room/moderate temperature. CO2 adsorption experiments were performed in a thermogravimetric analyzer (TGA). The adsorption performance of the adsorbents obtained from the mechanochemical reaction (BM-C/E-CaO) was superior to that of the adsorbents obtained from the thermochemical reaction (Cal-C/E-CaO). The CO2 adsorption capacity of BM-C-CaO at 650 °C is up to 36.82 wt%, but the adsorption decay rate of the sample after 20 carbonation/calcination cycles is only 30.17%. This study offers an alternative energy-saving method for greenly preparing CaO-based adsorbent from shell wastes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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9. [Microglia differential genes and their functions in paraquat-induced Parkinson's disease-like in mice's brains based on single-cell RNA sequencing].
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Guo ZK, Zhang YT, Zhang Y, Weng YL, Li HY, and Wu SY
- Subjects
- Animals, Mice, Male, Parkinson Disease genetics, Parkinson Disease metabolism, Disease Models, Animal, Signal Transduction, Sequence Analysis, RNA, Single-Cell Analysis, Transcriptome, Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases genetics, Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases metabolism, Gene Expression Profiling, Paraquat toxicity, Mice, Inbred C57BL, Microglia drug effects, Microglia metabolism, Brain metabolism, Brain drug effects
- Abstract
Objective: To analyze the differential genes and related signaling pathways of microglia subpopulations in Parkinson's disease (PD) -like mouse brains induced by paraquat (PQ) based on single-cell RNA sequencing, and provide clues to elucidate the mechanism of PQ-induced PD-like changes in the brain of animals. Methods: In September 2021, six male 6-week-old C57BL/6 mice were randomly divided into control group and experimental group (three mice in each group) . The mice were injected with saline, 10.0 mg/kg PQ intraperitoneally, once every three days, and 10 consecutive injections were used for modeling. After infection, the brains of mice were taken and 10×Genomics single-cell RNA sequencing was performed. Microglia subpopulations were screened based on gene expression characteristics, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The differential genes of microglia subpopulations between the experimental group and control group were further screened, and functional enrichment analysis was performed using bioinformatics tools. Mouse microglia (BV2 cells) were treated with 0, 60, 90 μmol/L PQ solution, respectively. And real-time fluorescence quantitative PCR experiments were conducted to validate the expressions of differential genes hexokinase 2 (Hk2) , ATPase H+ Transporting V0 Subunit B (Atp6v0b) and Neuregulin 1 (Nrg1) . Results: Cluster 7 and Cluster 20 were identified as microglia subpopulations based on the signature genes inositol polyphosphate-5-phosphatase d, Inpp5d (Inpp5d) and transforming growth factor beta receptor 1 (Tgfbr1) , and they reflected the microglia-activated M2 phenotype. The bioinformatics analysis showed that the characteristic genes of identified microglia subpopulations were enriched in endocytosis. In terms of molecular function, it mainly enriched in transmembrane receptor protein kinase activity and cytokine binding. The up-regulated genes of Cluster 7 were mainly enriched in lysosomal pathway, endocytosis pathway, and down-regulated genes were mainly enriched in neurodegenerative disease and other signaling pathways. The up-regulated genes of Cluster 20 were mainly enriched in signaling pathways related to PD, and down-regulated genes were mainly enriched in cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathways, neurological development, synaptic function and other signaling pathways. The results of real-time fluorescence quantitative PCR showed that the expressions of Hk2 mRNA and Atp6v0b mRNA increased and the expression of Nrg1 mRNA decreased in the 90 μmol/L PQ-treated BV2 cells compared with the 0 μmol/L, and the differences were statistically significant ( P <0.05) . Conclusion: Microglia are activated in the PQ-induced PD-like mouse model and polarized toward the M2 phenotype. And their functions are associated with lysosomal (endocytosis) , synaptic functions and the regulation of PD-related pathways.
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- 2024
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10. Clinical analysis of secondary penile cancer: a case series at a tertiary referral center in China.
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Li XY, Xu CR, Ji X, Zhu ZP, Guo ZK, Cai TY, and Lin J
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- Humans, Male, China epidemiology, Middle Aged, Aged, Adult, Carcinoma, Squamous Cell pathology, Neoplasms, Second Primary epidemiology, Neoplasms, Second Primary pathology, Penile Neoplasms pathology, Tertiary Care Centers
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- 2024
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11. Targeting Mitochondrial Dysfunction With LncRNAs in a Wistar Rat Model of Chronic Obstructive Pulmonary Disease.
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Lin QI, Zhang CF, Chen JY, Guo ZK, Wu SY, and Li HY
- Subjects
- Rats, Animals, Rats, Wistar, Particulate Matter, Mitochondria genetics, Mitochondria metabolism, Gene Expression Profiling, RNA, Long Noncoding genetics, Pulmonary Disease, Chronic Obstructive genetics
- Abstract
Background/aim: Chronic obstructive pulmonary disease (COPD) has become a prominent healthcare issue in recent years. Cigarette smoking (CS) and fine particulate matter (PM
2.5 ) are important causative factors for COPD. This study assessed the aberrant lncRNA profiles in the tissue of rats with COPD caused by CS or PM2.5 Materials and Methods: A COPD rat model was developed using CS (CSM) or PM2.5 (PMM), and lung tissue RNA was extracted. The Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) were used to investigate the correlations between the distinct lncRNAs and mRNA pathways. A coding-non-coding gene co-expression network (CNC) was constructed by establishing connections between differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) associated with mitochondrial dysfunction and the inflammatory response., Results: A quantitative real-time reverse transcription PCR (qRT-PCR) experiment was performed to verify the expression of the particular lncRNAs. Microarray analysis of lung tissue from the COPD model revealed that 123 and 444 lncRNAs were substantially raised and reduced in PMM vs. the control group (Ctrl), respectively, as were 621 and 1,178 mRNAs. Meanwhile, 81 and 340 lncRNAs were consistently raised and lowered in CSM vs. Ctrl, respectively, as were 408 and 931 mRNAs. GO enrichment and KEGG pathway analysis indicated that the COPD model was connected to inflammatory responses, mitochondrial dysfunction, and others., Conclusion: XR_340674, ENSRNOT00000089642, XR_597045, and XR_340651 were decreased, and XR_592469 was elevated. These lncRNAs were shown to be related to mitochondrial dysfunction in the lung tissue of animals exposed to CS or PM2.5 ., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)- Published
- 2023
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12. Global dynamics of a tuberculosis model with age-dependent latency and time delays in treatment.
- Author
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Guo ZK, Huo HF, Xiang H, and Ren QY
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- Humans, Basic Reproduction Number, Time Factors, Incidence, Computer Simulation, Models, Biological, Tuberculosis drug therapy, Tuberculosis epidemiology, Tuberculosis prevention & control
- Abstract
Since there exists heterogeneity in incubation periods of tuberculosis and a time lag between treatment and recovery. In this study, we develop a tuberculosis model that takes into account age-dependent latency and time delays in treatment to describe the transmission of tuberculosis. We first show that the solution semi-flow of the model is well-posed and has a global attractor [Formula: see text] within an infinite dimensional space [Formula: see text]. Then we define the basic reproduction number [Formula: see text] and prove that it determines the global dynamics of the model. If [Formula: see text], the global attractor [Formula: see text] reduces to the disease-free equilibrium state, indicating that the disease-free equilibrium state is globally asymptotically stable. When [Formula: see text], the semi-flow generated by the model is uniformly persistent, and there exists an interior global attractor [Formula: see text] for this uniformly persistent model. By constructing a suitable Lyapunov function and applying LaSalle's Invariance Principle, we show that the global attractor [Formula: see text] is reduced to the endemic equilibrium state, which means that the endemic equilibrium state is globally asymptotically stable. Based on the tuberculosis data in China from 2007 to 2020, we simulate the parameters and initial values of the proposed model. Furthermore, we calculate the sensitivity of [Formula: see text] to the parameters and find the most sensitive parameters to [Formula: see text]. Finally, we present an improved strategy to achieve the WHO's goal of reducing the incidence of tuberculosis by 90% by 2035 compared to 2015., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2023
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13. [Recent Progress on Pharmaceutical Properties of Extracellular Vesicles from Mesenchymal Stem Cells--Review].
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Liu YS, Sun Y, and Guo ZK
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- Humans, Hematopoietic Stem Cell Transplantation adverse effects, Mesenchymal Stem Cell Transplantation methods, Pharmaceutical Preparations, Extracellular Vesicles, Mesenchymal Stem Cells
- Abstract
Mesenchymal stem cells (MSCs) have been officially approved in many countries to treat graft-versus-host disease, autoimmune disorders and those associated with tissue regeneration after hematopoietic stem cell transplantation. Studies in recent years have confirmed that MSC acts mainly through paracrine mechanism, in which extracellular vesicles secreted by MSC (MSC-EV) play a central role. MSC-EV has overwhelming advantages over MSC itself in the setting of adverse effects in clinical application, indicating that MSC-EV might take the place of its parent cells to be a potentially therapeutic tool for "cell-free therapy". The pharmaceutical properties of MSC-EV largely depend upon the practical and optimal techniques including large-scale expansion of MSC, the modification of MSC based on the indications and the in vivo dynamic features of MSC-EV, and the methods for preparing and harvesting large amounts of MSC-EV. The recent progresses on the issues above will be briefly reviewed.
- Published
- 2023
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14. Comparison between different treatment regimens of vascular targeting drug to malignant pleural effusion in patients with lung cancer: A Bayesian network meta-analysis.
- Author
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Huang P, Guo ZK, and Xue ZT
- Subjects
- Humans, Bevacizumab, Bayes Theorem, Network Meta-Analysis, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Pleural Effusion, Malignant drug therapy, Pleural Effusion, Malignant etiology, Lung Neoplasms complications, Lung Neoplasms drug therapy
- Abstract
Background: The presence of malignant pleural effusion in lung cancer patients often suggests a poor prognosis. We plan to investigate which regimen of vascular targeting drug is preferable to control the malignant pleural effusion in such patients., Methods: Two investigators dependently searched and screened for randomized controlled trials in PubMed, Embase, Web of Science and China National Knowledge Infrastructure from the database inception to August 2022. R software was applied to build a network model in Bayesian method. Objective response rate of malignant pleural effusion is the primary outcome measure. Besides, the incidence of 3 adverse events were compared, including gastrointestinal reaction, leukopenia and hypertension. Due to the disconnection of network, we analysis and discuss the short-term treatment (3-4 weeks) and long-term treatment (6-12 weeks) respectively., Results: 31 studies with 2093 patients were identified. Four targeting drugs contain bevacizumab (Bev), anlotinib, apatinib and Endostar. Two administration routes include intracavity perfusion (icp) and intravenous injection. Based on the current evidence, for short-term treatments, compared with single-agent chemotherapy (CT), Bev_icp + CT, anlotinib + CT, Bev_icp and anlotinib + endorstar_icp present better objective response, and no statistical significance was found in objective response between Bev_icp + CT, anlotinib + CT and Bev_icp. For long-term treatments, compared with doublet or triplet chemotherapy (2CT or 3CT), Bev_icp + 2CT, apatinib + 2CT, Bev_icp + 3CT, and Bev_intravenous injection + 2CT are more effective option, but no statistical significance was found in objective response between the 4 combination regimens with chemotherapy., Conclusion: Our findings suggest that no statistical significance between above vascular targeting regimens. Pathological type of lung cancer may affect the effect of bevacizumab intracavity infusion plus chemotherapy. The influence of different administration routes of vascular targeting drugs on efficacy remains to be investigated. There are some concerns with the quality of the studies, and some limitations should be considered when interpreting these results, which includes limited geographical region and sample size of studies. Despite these limitations, this study may inform vascular targeting therapy choice in such a patient population., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2023
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15. Nagimycins A and B, Antibacterial Ansamycin-Related Macrolactams from Streptomyces sp. NA07423.
- Author
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Guo ZK, Wang YC, Tan YZ, Abulaizi A, Xiong ZJ, Zhang SQ, Yang Y, Yang Y, and Shi J
- Subjects
- Lactams, Macrocyclic chemistry, Anti-Bacterial Agents chemistry, Magnetic Resonance Spectroscopy, Rifabutin chemistry, Streptomyces chemistry
- Abstract
Chemical investigation of Streptomyces sp. NA07423 led to the discovery of two unreported macrolactams, nagimycins A ( 1 ) and B ( 2 ). Their structures were elucidated by NMR, HRESIMS, X-ray crystallography, and comparison of experimental and theoretical ECD spectra. The nagimycins have a unique butenolide moiety rarely found in ansamycin antibiotics. Genome analysis revealed the putative biosynthetic gene cluster for nagimycins, and a likely biosynthetic pathway was proposed. Notably, compounds 1 and 2 exhibited potent antibacterial activity against two pathogenic Xanthomonas bacteria.
- Published
- 2023
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16. Apolipoprotein E2 inhibits mitochondrial apoptosis in pancreatic cancer cells through ERK1/2/CREB/BCL-2 signaling.
- Author
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Wang H, Zhou HC, Ren RL, Du SX, Guo ZK, and Shen XH
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- Humans, Apolipoprotein E2 metabolism, Apoptosis, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-2 metabolism, Proto-Oncogene Proteins c-bcl-2 therapeutic use, Cyclic AMP Response Element-Binding Protein metabolism, Pancreatic Neoplasms, MAP Kinase Signaling System, Pancreatic Neoplasms drug therapy
- Abstract
Background: Apolipoprotein E2 (ApoE2) is a pleiotropic protein that influences several aspects of cancer metabolism and development. Evading apoptosis is a vital factor for facilitating cancer cell growth. However, the role and mechanism of ApoE2 in regulating cell apoptosis of pancreatic cancer remain unclear., Methods: In this study, we firstly detected the mRNA and protein expressions of ApoE2 in PANC-1 and Capan-2 cells by real-time polymerase chain reaction and Western blotting. We then performed TUNEL and flow cytometric analyses to explore the role of recombinant human ApoE2, pCMV6-ApoE2 and siApoE2 in the apoptosis of PANC-1 and Capan-2 cells. Furthermore, we investigated the molecular mechanism through which ApoE2 affected apoptosis in PANC-1 cells using immunofluorescence, immunoprecipitation, Western blotting and co-immunoprecipitation analysis., Results: ApoE2 phosphorylated ERK1/2 and inhibited pancreatic cancer cell apoptosis. In addition, our data showed that ApoE2/ERK1/2 altered the expression and mitochondrial localization of BCL-2 via activating CREB. ApoE2/ERK1/2/CREB also increased the total BCL-2/BAX ratio, inhibited the opening of the mitochondrial permeability transition pore and the depolarization of mitochondrial transmembrane potential, blocked the leakage of cytochrome-c and the formation of the apoptosome, and consequently, suppressed mitochondrial apoptosis., Conclusions: ApoE2 regulates the mitochondrial localization and expression of BCL-2 through the activation of the ERK1/2/CREB signaling cascade to evade the mitochondrial apoptosis of pancreatic cancer cells. ApoE2 may be a distinct prognostic marker and a potential therapeutic target for pancreatic cancer., (Copyright © 2022. Published by Elsevier B.V.)
- Published
- 2023
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17. Total Biosynthesis of Mutaxanthene Unveils a Flavoprotein Monooxygenase Catalyzing Xanthene Ring Formation.
- Author
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Xiang L, Shi J, Zhu A, Xu ZF, Liu SH, Wang YS, Guo ZK, Jiao RH, Tan RX, and Ge HM
- Subjects
- Polyketide Synthases metabolism, Mixed Function Oxygenases genetics, Mixed Function Oxygenases metabolism, Secondary Metabolism, Polyketides chemistry, Biological Products chemistry
- Abstract
Flavoprotein monooxygenases (FPMOs) play important roles in generating structural complexity and diversity in natural products biosynthesized by type II polyketide synthases (PKSs). In this study, we used genome mining to discover novel mutaxanthene analogues and investigated the biosynthesis of these aromatic polyketides and their unusual xanthene framework. We determined the complete biosynthetic pathway of mutaxathene through in vivo gene deletion and in vitro biochemical experiments. We show that a multifunctional FPMO, MtxO4, catalyzes ring rearrangement and generates the required xanthene ring through a multistep transformation. In addition, we successfully obtained all necessary enzymes for in vitro reconstitution and completed the total biosynthesis of mutaxanthene in a stepwise manner. Our results revealed the formation of a rare xanthene ring in type II polyketide biosynthesis, and demonstrate the potential of using total biosynthesis for the discovery of natural products synthesized by type II PKSs., (© 2023 Wiley-VCH GmbH.)
- Published
- 2023
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18. Constraining First-Order Phase Transitions with Curvature Perturbations.
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Liu J, Bian L, Cai RG, Guo ZK, and Wang SJ
- Abstract
The randomness of the quantum tunneling process induces superhorizon curvature perturbations during cosmological first-order phase transitions. We for the first time utilize curvature perturbations to constrain the phase transition parameters, and find that the observations of the cosmic microwave background spectrum distortion and the ultracompact minihalo abundance can give strict constraints on the phase transitions below 100 GeV, especially for the low-scale phase transitions and some electroweak phase transitions. The current constraints on the phase transition parameters are largely extended by the results of this work, therefore provide an novel approach to probe related new physics.
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- 2023
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19. Resistance and phylogeny guided discovery reveals structural novelty of tetracycline antibiotics.
- Author
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Li LY, Hu YL, Sun JL, Yu LB, Shi J, Wang ZR, Guo ZK, Zhang B, Guo WJ, Tan RX, and Ge HM
- Abstract
Tetracyclines are a class of antibiotics that exhibited potent activity against a wide range of Gram-positive and Gram-negative bacteria, yet only five members were isolated from actinobacteria, with two of them approved as clinical drugs. In this work, we developed a genome mining strategy using a TetR/MarR-transporter, a pair of common resistance enzymes in tetracycline biosynthesis, as probes to find the potential tetracycline gene clusters in the actinobacteria genome database. Further refinement using the phylogenetic analysis of chain length factors resulted in the discovery of 25 distinct tetracycline gene clusters, which finally resulted in the isolation and characterization of a novel tetracycline, hainancycline (1). Through genetic and biochemical studies, we elucidated the biosynthetic pathway of 1, which involves a complex glycosylation process. Our work discloses nature's huge capacity to generate diverse tetracyclines and expands the chemical diversity of tetracyclines., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)
- Published
- 2022
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20. "Reverse life": A rare case report of situs inversus totalis combined with cardiac abnormalities in a young stroke.
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Chen XQ, Lin SJ, Wang JJ, Long S, Kong FX, and Guo ZK
- Subjects
- Humans, Tomography, X-Ray Computed, Situs Inversus complications, Situs Inversus diagnostic imaging, Stroke complications, Stroke diagnostic imaging
- Published
- 2022
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21. [Expression and significance of fibroblast growth factor receptor 2 in clear cell renal cell carcinoma].
- Author
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Cai TY, Zhu ZP, Xu CR, Ji X, Lv TD, Guo ZK, and Lin J
- Subjects
- Biomarkers, Tumor analysis, Humans, Prognosis, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology, Receptor, Fibroblast Growth Factor, Type 2 genetics
- Abstract
Objective: To investigate the expression of fibroblast growth factor receptor 2 ( FGFR2 ) in clear cell renal cell carcinoma (ccRCC; or kidney renal clear cell carcinoma, KIRC), to analyze the relationship between the expression of FGFR2 and the clinical pathological features and prognosis of ccRCC, to study the relationship between the expression of FGFR2 and other molecules, and to explore its role in the development of ccRCC., Methods: Gene expressional and clinical information of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus(GEO) database. Next, the data were transformed and collated. In the study, 104 clinical ccRCC samples and corresponding paracancerous normal tissue samples were collected from Department of Urology, Peking University First Hospital. Immunohistochemistry (IHC) was performed and the staining results were scored, so as to compare the expression of FGFR2 in ccRCC and paracancerous normal tissues. Besides, quantify real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression level of FGFR2 in normal renal epithelial cell lines (293) and ccRCC cell lines (786-O, 769-P, OSRC-2, Caki-1, ACHN, and A498). In addition, the relationship between FGFR2 expression and clinical pathological characteristics (including TNM staging and pathological grading) and survival prognosis in ccRCC patients was further analyzed. Furthermore, the relationship between FGFR2 expression and B cells, T cells, natural killer (NK) cells and neutrophil infiltration in the ccRCC patients was analyzed, and the Biological General Repository for Interactionh Datasets (BioGRID) was used to builds protein-protein interaction (PPI) networks to study molecules that interacted with the FGFR2 protein., Results: In the TCGA database, the expression of FGFR2 was down-regulated in ccRCC tissue samples compared with normal tissue samples, and the expression in the GEO database also showed this differences. Furthermore, FGFR2 expression was downregulated in ccRCC clinical samples and ccRCC cell lines, compared with corresponding paracancerous normal tissue or normal renal epithelial cell lines. In addition, FGFR2 high expression was associated with earlier, lower-level ccRCC and was associated with a better prognosis in the patients with ccRCC. Moreover, FGFR2 expression was not significantly related to B cells, T cells, NK cells and neutrophil infiltration, and the PPI network showed that FGFR2 protein interacted with certain molecules., Conclusion: Our work sheds light on the potential role of FGFR2 in the development of ccRCC, suggesting that FGFR2 may serve as a prognostic marker and potential therapeutic target for patients with ccRCC.
- Published
- 2022
22. Biosynthesis of Sordarin Revealing a Diels-Alderase for the Formation of the Norbornene Skeleton.
- Author
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Liu SH, Sun JL, Hu YL, Zhang L, Zhang X, Yan ZY, Guo X, Guo ZK, Jiao RH, Zhang B, Tan RX, and Ge HM
- Subjects
- Norbornanes, Skeleton, Diterpenes chemistry, Indenes chemistry
- Abstract
Sordarin (1) is a fungal diterpene glycoside that displays potent antifungal bioactivity through inhibition of elongation factor 2. The structures of sordarin and related compounds feature a highly rearranged tetracyclic diterpene core. In this study, we identified a concise pathway in the biosynthesis of sordarin. A diterpene cyclase (SdnA) generates the 5/8/5 cycloaraneosene framework, which is decorated by a set of P450s that catalyze a series of oxidation reactions, including hydroxylation, desaturation, and C-C bond oxidative cleavage, to give a carboxylate intermediate with a terminal alkene and a cyclopentadiene moiety. A novel Diels-Alderase SdnG catalyzes an intramolecular Diels-Alder (IMDA) reaction on this intermediate to forge the sordarin core structure. Subsequent methyl hydroxylation and glycosylation complete the biosynthesis of sordarin. Our work discloses a new strategy used by nature for the formation of the rearranged diterpene skeleton., (© 2022 Wiley-VCH GmbH.)
- Published
- 2022
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23. New antibacterial depsidones from an ant-derived fungus Spiromastix sp. MY-1.
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Guo ZK, Zhu WY, Zhao LX, Chen YC, Li SJ, Cheng P, Ge HM, Tan RX, and Jiao RH
- Subjects
- Animals, Anti-Bacterial Agents, Depsides, Fungi, Lactones, Microbial Sensitivity Tests, Molecular Structure, Ants, Bromides
- Abstract
Six new (1-6) and seven known depsidones (7-13) were isolated from the culture of an ant (Monomorium chinensis)-derived fungus Spiromastix sp. MY-1. Their structures were elucidated by extensive spectroscopic analysis including high resolution MS, 1D and 2D NMR data. The new bromide depsidones were obtained through supplementing potassium bromide in the fermentation medium of Spiromastix sp. MY-1. All isolated compounds showed various bioactivities against the tested phytopathogenic bacteria. Particularly, new bromide compound 4, named spiromastixone S, exhibited the strongest activity against Xanthomonas oryzae pv. oryzae with a MIC value of 5.2 μmol·
-1 ., (Copyright © 2022 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)- Published
- 2022
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24. [Clinical Safety of NK Cell in the Prevention of Leukemia Relapse Post-transplantation and in Treatment of the Elderly Leukemia Patients].
- Author
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Liu J, Zheng XL, Xue M, Zhu L, Ding L, Han DM, Yan HM, Li S, Ma JD, Tan XT, Zhou JX, Guo ZK, and Wang HX
- Subjects
- Aged, Humans, Killer Cells, Natural, Middle Aged, Recurrence, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy
- Abstract
Objective: To observe the safety of donor NK cell infusions in the settings of hematopoietic stem cell transplantation and after consolidation chemotherapy in elderly patients with acute myeloid leukemia (AML)., Methods: Forty patients with AML were included, in which 21 patients aged over 60 years were at the stage of complete remission (CR) and 19 patients that received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mononucleated cells were isolated from peripheral blood from the donors (for allo-HSCT) or healthy immediate family members (elderly AML). The cells were seeded into the flasks pre-coated with NK cell specific activators, and expanded in media containing recombinant human IL-15 and IL-2 for 14 days. The cells were transfused intravenously after the identification of quality control. Trypan blue exclusion test was used for the determination of cell viability and counting. Flow cytometry analysis was performed to assess the surface antigenic profile. Seventy-eight infusions of the cell products were received by the elderly patients with AML after consolidation chemotherapy, 11 infusions were received by the patients during allo-HSCT and 32 infusions 3 moths after transplantation. The safety of cell therapy, body temperature, blood pressure and other indexes were observe during and 48 hours after cell transfusion. Meanwhile, the occurrence and severity of acute graft-versus-host disease (GVHD) were documented., Results: Flow cytometry analysis showed that the proportion of NK cells (CD3
- CD56+ ) in the mononucleated cells before culture was (14.10±4.22)% (n=121), and the proportion increased dramatically up to (87.29±8.75)% (n=121) after culture for 14 days, the number of NK cells increased to 753.47±140.13 times (n=121). The doses of the infused NK cells was (7.58±2.50)×107 /kg per infusion. Moderate fever occurred in three cases after multiple infusions, and the temperature restored to normal on the same day after treatment. Fever was observed in one patient after every infusion of four times in total. The temperature reached to 38.5-39.0 ℃ and returned to normal within 1-2 hours after adequate antipyretic treatment, and then there was no discomfort. No GVHD was observed in the elderly AML patients, while 6 cases that received allo-HSCT developed moderate acute GVHD, among them grade I in 5 cases and grade II in 1 case. No other severe toxicities were observed., Conclusion: NK cell products with a high-purity could be obtained by ex vivo expansion with this protocol. The transfusion of these expanded cells is generally safe in the elderly patients with AML that have received chemotherapy or patients that received hematopoietic stem cell transplantation.- Published
- 2022
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25. Infusion of haploidentical HSCs combined with allogenic MSCs for the treatment of ALL patients.
- Author
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Ding L, Han DM, Yan HM, Zhou JX, Zheng XL, Zhu L, Xue M, Liu J, Mao N, Guo ZK, Ning HM, Wang HX, and Zhu H
- Subjects
- Acute Disease, Humans, Neoplasm Recurrence, Local, Transplantation Conditioning adverse effects, Graft vs Host Disease, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation adverse effects, Mesenchymal Stem Cells, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Although haploidentical stem cell transplantation (haplo-HSCT) offers almost all acute lymphoblastic leukaemia (ALL) patients an opportunity for immediate transplantation, it exhibits a higher incidence of graft failure and graft versus host disease (GVHD). Mesenchymal stem cells (MSCs) are characterised by their haematopoiesis-promoting and immunomodulatory capacity. Thus, we designed a combination of haplo-HSCT and MSCs for ALL patients. ALL patients (n = 110) were given haploidentical HSCs combined with allogenic MSCs, and ALL patients without MSC infusion (n = 56) were included as controls. The 100-day cumulative incidences of grade ≥2 acute GVHD (aGVHD) and grade ≥3 aGVHD were 40.00% and 9.09% compared to 42.32% (P = 0.79) and 22.79% (P = 0.03) in patients without MSC infusion, respectively. The 3-year cumulative incidences of chronic GVHD (cGVHD) and extensive cGVHD were 22.27% and 10.27% compared to 32.14% (P = 0.19) and 22.21% (P = 0.04) in patients without MSC infusion, respectively. No significant differences in the 3-year relapse incidence, nonrelapse mortality, leukaemia-free survival or overall survival in groups with and without MSC cotransplantation were observed. Multivariate analysis showed that MSC infusion contributed to a lower risk of developing extensive cGVHD. Our data suggested that haplo-HSCT combined with MSCs may provide an effective and safe treatment for ALL patients., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2022
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26. Involvement of NEAT1 /PINK1-mediated mitophagy in chronic obstructive pulmonary disease induced by cigarette smoke or PM 2.5 .
- Author
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Lin Q, Zhang CF, Guo JL, Su JL, Guo ZK, and Li HY
- Abstract
Background: This study sought to explore the underlying mechanism of long non-coding ribonucleic acid nuclear enriched abundant transcript 1 ( NEAT1 ) and PTEN-induced kinase 1 (PINK1)-mediated mitophagy in chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS) or fine particular matter (PM
2.5 )., Methods: In total, 30 male Wistar Rats were divided into the following 3 groups: (I) the COPD group exposed to CS (CSM); (II) the COPD group exposed to PM2.5 (PMM); and (III) the control (Ctrl) group. Pulmonary function, the enzyme-linked immunoassay analysis results, the histopathology results, and the ultrastructures of the lung tissues were examined in the 3 groups, and NEAT1 expression levels and the mitophagy-related protein PINK1, Parkin, LC3B, and p62 levels were assessed by quantitative reverse transcription PCR (RT-qPCR) and Western blotting. The A549 cells were transfected with small interfering ribonucleic acid (siRNA) targeting NEAT1, and subsequently stimulated with CS extract (CSE) and PM2.5 suspension (PMS). Mitochondrial dysfunction and enhanced mitophagy were observed, and the expression of the NEAT1 /PINK1 pathway was assessed by RT-qPCR and Western blotting., Results: Both the CSM and PMM groups had a lower tidal volume (VT ), minute ventilation (MV), and a higher respiratory rate (f) than the Ctrl group. The interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha levels in the serum and bronchoalveolar lavage fluid of the CSM and PMM groups were significantly increased. The histological examination results revealed airway remodeling, the formation of pulmonary bullae, and emphysema in the CSM and PMM groups. Subsequently, the ultrastructures of the lung tissues in the CSM and PMM groups showed mitochondrial swelling and autophagosomes. Additionally, NEAT1 expression, the level of the mitophagy-related protein PINK1, Parkin, and the ratio of LC3-II/I increased synchronously. Further, NEAT1 siRNA blocked PINK1 expression, inhibited mitochondrial dysfunctions, and mitophagy activation in the A549 cells exposed to CSE or PMS., Conclusions: Our results suggest that CS and PM2.5 exposure induce mitochondrial dysfunction, and the NEAT1 /PINK1 pathway plays a critical role in the occurrence and development of COPD by regulating mitophagy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-542/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)- Published
- 2022
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27. Infusion of haploidentical hematopoietic stem cells combined with mesenchymal stem cells for treatment of severe aplastic anemia in adult patients yields curative effects.
- Author
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Ding L, Han DM, Zheng XL, Yan HM, Xue M, Liu J, Zhu L, Guo ZK, Mao N, Ning HM, Wang HX, and Heng Zhu
- Subjects
- Hematopoietic Stem Cells, Humans, Transplantation Conditioning, Anemia, Aplastic therapy, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Mesenchymal Stem Cells
- Abstract
Background Aims: Despite the great advances in immunosuppressive therapy for severe aplastic anemia (SAA), most patients are not completely cured. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been recommended as an alternative treatment in adult SAA patients. However, haplo-HSCT presents a higher incidence of graft failure and graft-versus-host disease (GVHD). The authors designed a combination of haplo-HSCT and umbilical cord-derived mesenchymal stem cells (UC-MSCs) for treatment of SAA in adult patients and evaluated its effects., Methods: Adult patients (≥18 years) with SAA (N = 25) were given HLA-haploidentical hematopoietic stem cells (HSCs) combined with UC-MSCs after a conditioning regimen consisting of busulfan, cyclophosphamide, fludarabine and anti-thymocyte globulin and intensive GVHD prophylaxis, including cyclosporine, basiliximab, mycophenolate mofetil and short-term methotrexate. Additionally, the effects of the protocol in adult SSA patients were compared with those observed in juvenile SAA patients (N = 75)., Results: All patients achieved myeloid engraftment after haplo-HSCT at a median of 16.12 days (range, 11-26). The median time of platelet engraftment was 28.30 days (range, 13-143). The cumulative incidence of grade II acute GVHD (aGVHD) at day +100 was 32.00 ± 0.91%. No one had grade III-IV aGVHD at day +100. The cumulative incidence of total chronic GVHD was 28.00 ± 0.85%. The overall survival was 71.78 ± 9.05% at a median follow-up of 42.08 months (range, 2.67-104). Promisingly, the protocol yielded a similar curative effect in both young and adult SAA patients., Conclusions: The authors' data suggest that co-transplantation of HLA-haploidentical HSCs and UC-MSCs may provide an effective and safe treatment for adult SAA., (Copyright © 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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28. An NADPH-Dependent Ketoreductase Catalyses the Tetracyclic to Pentacyclic Skeletal Rearrangement in Chartreusin Biosynthesis.
- Author
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Jiao FW, Wang YS, You XT, Wei W, Chen Y, Yang CL, Guo ZK, Zhang B, Liang Y, Tan RX, Jiao RH, and Ge HM
- Abstract
Redox tailoring enzymes play key roles in generating structural complexity and diversity in type II polyketides. In chartreusin biosynthesis, the early
13 C-labeling experiments and bioinformatic analysis suggest the unusual aglycone is originated from a tetracyclic anthracyclic polyketide. Here, we demonstrated that the carbon skeleton rearrangement from a linear anthracyclic polyketide to an angular pentacyclic biosynthetic intermediate requires two redox enzymes. The flavin-dependent monooxygenase ChaZ catalyses a Baeyer-Villiger oxidation on resomycin C to form a seven-membered lactone. Subsequently, a ketoreductase ChaE rearranges the carbon skeleton and affords the α-pyrone containing pentacyclic intermediate in an NADPH-dependent manner via tandem reactions including the reduction of the lactone carbonyl group, Aldol-type reaction, followed by a spontaneous γ-lactone ring formation, oxidation and aromatization. Our work reveals an unprecedented function of a ketoreductase that contributes to generate structural complexity of aromatic polyketide., (© 2021 Wiley-VCH GmbH.)- Published
- 2021
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29. Discovery of an unprecedented benz[α]anthraquinone-type heterodimer from a rare actinomycete Amycolatopsis sp. HCa1.
- Author
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Xu Y, Xie J, Wu WC, Chen BT, Zhang SQ, Wang R, Huang J, and Guo ZK
- Subjects
- Animals, Anthraquinones isolation & purification, Antineoplastic Agents isolation & purification, Biological Products isolation & purification, Biological Products pharmacology, Cell Line, Tumor, China, Dimerization, Drug Screening Assays, Antitumor, Humans, Molecular Structure, Polyketides isolation & purification, Polyketides pharmacology, Amycolatopsis chemistry, Anthraquinones pharmacology, Antineoplastic Agents pharmacology, Grasshoppers microbiology
- Abstract
The angucylines are a family of aromatic polyketides featuring a tetracyclic benz[a]anthraquinone skeleton. This class of polycyclic aromatic polyketides are exclusively associated with actinomycetes and can undergo many modifications such as oxidation, ring cleavage, glycosylation and dimerization. Here we report the discovery of a new ether-linked benz[a]anthraquinone heterodimer, named mycolatone (1), from a grasshopper-derived actinomycete, Amycolatopsis sp. HCa1. The structure of mycolatone (1) was determined by comprehensive two-dimensional NMR analysis, high-resolution electrospray ionization mass spectrometry and biogenetic consideration. This new heterodimeric molecule is structurally derived from the dimerization of two tetracyclic angucylines, 2-hydroxy-5-O-methyltetragomycin and PD116779, through an ether bond between C-8 and C-8'. This new structural feature enrich the structural diversity of angucylines. Additionally, the surface tension activity and cytotoxic activities of 1 against human cervical cancer cell line (Hela), human gastric adenocarcinoma cell line (SGC-7901) and human lung adenocarcinoma cell line (SPC-A-1) were evaluated., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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30. Whole-body magnetic resonance imaging vs. clinical evaluation of enthesitis in patients with spondyloarthritis.
- Author
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Guo ZK, Zhang YM, Kong CY, Liu Y, Ji XD, Zhan Y, Qi WF, and Lei XW
- Subjects
- Humans, Severity of Illness Index, Whole Body Imaging, Magnetic Resonance Imaging, Spondylarthritis diagnostic imaging
- Published
- 2021
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31. Large Anisotropies of the Stochastic Gravitational Wave Background from Cosmic Domain Walls.
- Author
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Liu J, Cai RG, and Guo ZK
- Abstract
We investigate the stochastic gravitational wave background (SGWB) from cosmic domain walls (DWs) caused by quantum fluctuations of a light scalar field ϕ during inflation. Large-scale perturbations of ϕ lead to large-scale perturbations of DW energy density and anisotropies in the SGWB. We find that the angular power spectrum of this SGWB is scale invariant and at least of the order of 10^{-2}, which is a distinctive feature of observational interest. Since we have not detected primordial gravitational waves yet, anisotropies of the SGWB provide a nontrivial opportunity to verify the rationality of inflation and detect the energy scale of inflation, especially for low-scale inflationary models. Square kilometer array has the opportunity to detect the anisotropies of such SGWBs. The common-spectrum process observed recently by NANOGrav could also be interpreted by the SGWB from cosmic DWs.
- Published
- 2021
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32. Analysis of an age-structured tuberculosis model with treatment and relapse.
- Author
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Guo ZK, Xiang H, and Huo HF
- Subjects
- Basic Reproduction Number, China, Computer Simulation, Humans, Recurrence, Models, Biological, Tuberculosis
- Abstract
A new tuberculosis model consisting of ordinary differential equations and partial differential equations is established in this paper. The model includes latent age (i.e., the time elapsed since the individual became infected but not infectious) and relapse age (i.e., the time between cure and reappearance of symptoms of tuberculosis). We identify the basic reproduction number [Formula: see text] for this model, and show that the [Formula: see text] determines the global dynamics of the model. If [Formula: see text], the disease-free equilibrium is globally asymptotically stable, which means that tuberculosis will disappear, and if [Formula: see text], there exists a unique endemic equilibrium that attracts all solutions that can cause the spread of tuberculosis. Based on the tuberculosis data in China from 2007 to 2018, we use Grey Wolf Optimizer algorithm to find the optimal parameter values and initial values of the model. Furthermore, we perform uncertainty and sensitivity analysis to identify the parameters that have significant impact on the basic reproduction number. Finally, we give an effective measure to reach the goal of WHO of reducing the incidence of tuberculosis by 80% by 2030 compared to 2015.
- Published
- 2021
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- View/download PDF
33. Hubble parameter estimation via dark sirens with the LISA-Taiji network.
- Author
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Wang R, Ruan WH, Yang Q, Guo ZK, Cai RG, and Hu B
- Abstract
The Hubble parameter is one of the central parameters in modern cosmology, and describes the present expansion rate of the universe. The values of the parameter inferred from late-time observations are systematically higher than those inferred from early-time measurements by about [Formula: see text]. To reach a robust conclusion, independent probes with accuracy at percent levels are crucial. Gravitational waves from compact binary coalescence events can be formulated into the standard siren approach to provide an independent Hubble parameter measurement. The future space-borne gravitational wave observatory network, such as the LISA-Taiji network, will be able to measure the gravitational wave signals in the millihertz bands with unprecedented accuracy. By including several statistical and instrumental noises, we show that, within a five-year operation time, the LISA-Taiji network is able to constrain the Hubble parameter within [Formula: see text] accuracy, and possibly beats the scatters down to [Formula: see text] or even better., (© The Author(s) 2021. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)
- Published
- 2021
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34. A study of human leukocyte antigen-haploidentical hematopoietic stem cells transplantation combined with allogenic mesenchymal stem cell infusion for treatment of severe aplastic anemia in pediatric and adolescent patients.
- Author
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Ding L, Han DM, Zheng XL, Yan HM, Xue M, Liu J, Zhu L, Li S, Mao N, Guo ZK, Ning HM, Wang HX, and Zhu H
- Subjects
- Adolescent, Child, HLA Antigens, Humans, Transplantation Conditioning, Anemia, Aplastic therapy, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation adverse effects, Mesenchymal Stem Cell Transplantation
- Abstract
The clinical applications of human leukocyte antigen (HLA) haploidentical hematopoietic stem cells transplantation (haplo-HSCT) have offered most of the young severe aplastic anemia (SAA) patients an opportunity to accept curative therapy at the early stage of bone marrow lesions. However, the outcome of juvenile SAA patients received haplo-HSCT remain to be improved due to high incidence of graft failure and graft vs host disease (GVHD). Mesenchymal stem cells (MSCs) have been characterized by their hematopoiesis-supporting and immunomodulatory properties. In the current study, we designed a combination of haplo-HSCT with allogenic MSC for treatment of SAA in pediatric and adolescent patients and evaluated its effects. Juvenile patients (<18 years) with SAA (n = 103) were given HLA-haploidentical HSC combined with allogenic MSC after a conditioning regimen consisting of busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin and an intensive GVHD prophylaxis, including cyclosporine, short-term methotrexate, mycophenolate mofetil, and basiliximab. Neutrophil engraftment was achieved in 102 of 103 patients in a median time of 14.3 days (range 9-25 days). The median time of platelet engraftment was 25.42 days (range 8-93 days). The cumulative incidence of II-IV acute GVHD at day +100 was 26.32% ± 0.19% and III-IV acute GVHD was 6.79% ± 0.06% at day +100, respectively. The cumulative incidence of chronic GVHD was 25.56% ± 0.26%. The overall survival was 87.15% ± 3.3% at a median follow-up of 40 (1.3-98) months. Our data suggest that cotransplantation of HLA-haploidentical HSC and allogenic mesenchymal stem cell may provide an effective and safe treatment for children and adolescents with SAA who lack matched donors., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)
- Published
- 2021
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35. The LISA-Taiji Network: Precision Localization of Coalescing Massive Black Hole Binaries.
- Author
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Ruan WH, Liu C, Guo ZK, Wu YL, and Cai RG
- Abstract
We explore a potential LISA-Taiji network to fast and accurately localize the coalescing massive black hole binaries. For an equal-mass binary located at redshift of 1 with a total intrinsic mass of 10
5 M⊙ , the LISA-Taiji network may achieve almost four orders of magnitude improvement on the source localization region compared to an individual detector. The precision measurement of sky location from the gravitational-wave signal may completely identify the host galaxy with low redshifts prior to the final black hole merger. Such identification of the host galaxy is vital for the follow-up variability in electromagnetic emissions of the circumbinary disc when the binary merges to a new black hole and enables the coalescing massive black hole binaries to be used as a standard siren to probe the expansion history of the Universe., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2021 Wen-Hong Ruan et al.)- Published
- 2021
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36. [Establishment of A Novel Method to Activate and Expand Human NK Cells Ex Vivo].
- Author
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Qian KC, Ge SH, Jie FJ, Guo ZK, and Zhang DP
- Subjects
- Flow Cytometry, Humans, K562 Cells, Cell Culture Techniques, Killer Cells, Natural
- Abstract
Objective: To develop a new method to activate and expand human NK cells ex vivo by using sodium hyaluronate as a major activating agent and to explore its related mechanism., Methods: Mononuclear cells were isolated from 3 samples of peripheral blood from three healthy donors. New NK cell culture method and the control method were used to culture NK cells from each samples separately for 14 days. Flow cytometry was used to analyze the ratio of NK cells and CD69 expression. To measure the in vitro cytotoxicity of NK cells cultured by the two methods, the K562 cells were used as the targeting cells and flow cytometry combined with CFSE marker was used as the testing method., Results: After culturing for 14 days, the number of NK cells obtained by new culture method for NK cells expanded by 188.63±3.83 times while the number of NK cells cultured by control method expanded by 152.77±5.77 times. The ratio of NK cells in new cell culture method was above 90%, while the ratio of NK cells in control method was about 70%. The ratio of CD69+ NK cells in new cell culture method was 32.37%±3.22%, while the ratio of CD69+ NK cells in control method was 17.29%±3.79%. The results of cytotoxicity experiment in vitro showed that NK cells cultured by the new method had a higher killing ability to the target cells as compared with NK cells cultured by the control method., Conclusion: New NK cell culture method using sodium hyaluronate as a major activating agent can expand NK cells more efficiently as compared with the cells cultured by control method, which may be related to the direct and/or indirect activation of sodium hyaluronate to NK cells, further causing the dominant expansion of the NK cells.
- Published
- 2020
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37. SphK2 confers 5-fluorouracil resistance to colorectal cancer via upregulating H3K56ac-mediated DPD expression.
- Author
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Zhang YH, Shi WN, Wu SH, Miao RR, Sun SY, Luo DD, Wan SB, Guo ZK, Wang WY, Yu XF, Cui SX, and Qu XJ
- Subjects
- Animals, Colorectal Neoplasms pathology, Fluorouracil pharmacology, Humans, Mice, Up-Regulation, Colorectal Neoplasms genetics, Dihydrouracil Dehydrogenase (NADP) metabolism, Drug Resistance, Neoplasm genetics, Fluorouracil therapeutic use, Phosphotransferases (Alcohol Group Acceptor) metabolism
- Abstract
Aberrant sphingolipid metabolism has been implicated in chemoresistance, but the underlying mechanisms are still poorly understood. Herein we revealed a previously unrecognized mechanism of 5-fluorouracil (5-FU) resistance contributed by high SphK2-upregulated dihydropyrimidine dehydrogenase (DPD) in colorectal cancer (CRC), which is evidenced from human CRC specimens, animal models, and cancer cell lines. TMA samples from randomly selected 60 CRC specimens firstly identified the clinical correlation between high SphK2 and increased DPD (p < 0.001). Then the regulatory mechanism was explored in CRC models of villin-SphK2 Tg mice, SphK2
-/- mice, and human CRC cells xenografted nude mice. Assays of ChIP-Seq and luciferase reporter gene demonstrated that high SphK2 upregulated DPD through promoting the HDAC1-mediated H3K56ac, leading to the degradation of intracellular 5-FU into inactive α-fluoro-β-alanine (FBAL). Lastly, inhibition of SphK2 by SLR080811 exhibited excellent inhibition on DPD expression and potently reversed 5-FU resistance in colorectal tumors of villin-SphK2 Tg mice. Overall, this study manifests that SphK2high conferred 5-FU resistance through upregulating tumoral DPD, which highlights the strategies of blocking SphK2 to overcome 5-FU resistance in CRC.- Published
- 2020
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38. Tumor necrosis factor α in aGVHD patients contributed to the impairment of recipient bone marrow MSC stemness and deficiency of their hematopoiesis-promotion capacity.
- Author
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Ding L, Ning HM, Li PL, Yan HM, Han DM, Zheng XL, Liu J, Zhu L, Xue M, Mao N, Guo ZK, Zhu H, and Wang HX
- Subjects
- Bone Marrow, Bone Marrow Cells, Hematopoiesis, Humans, Tumor Necrosis Factor-alpha genetics, Graft vs Host Disease, Mesenchymal Stem Cells
- Abstract
Background: Though accumulated evidence has demonstrated visceral organ involvement in acute graft-versus-host disease (aGVHD), how aGVHD influences the bone marrow (BM) niche and the reconstitution of hematopoiesis post-hematopoietic stem cell transplantation remains largely unknown., Methods: In the current study, the cell morphology, immunophenotype, multi-differentiation capacity, self-renewal capacity, and hematopoiesis promotion of the MSCs from aGVHD and non-aGVHD patients were investigated. Additionally, the stemness and hematopoiesis-promoting property of healthy donor-derived MSCs were evaluated in the presence of BM supernatant from aGVHD patients. Mechanistically, antibodies targeting inflammatory cytokines involved in aGVHD were added into the MSC culture. Furthermore, a recombinant human tumor necrosis factor (TNF-α) receptor-Ig fusion protein (rhTNFR:Fc) was used to protect healthy donor-derived MSCs. Moreover, mRNA sequencing was performed to explore the underlying mechanisms., Results: The aGVHD MSCs exhibited morphological and immunophenotypic characteristics that were similar to those of the non-aGVHD MSCs. However, the osteogenic and adipogenic activities of the aGVHD MSCs significantly decreased. Additionally, the colony formation capacity and the expression of self-renewal-related genes remarkably decreased in aGVHD MSCs. Further, the hematopoiesis-supporting capacity of aGVHD MSCs significantly reduced. The antibody neutralization results showed that TNF-α contributed to the impairment of MSC properties. Moreover, rhTNFR:Fc exhibited notable protective effects on MSCs in the aGVHD BM supernatants. The mRNA sequencing results indicated that the TNF-α pathway and the Toll-like receptor pathway may be activated by TNF-α., Conclusions: Thus, our data demonstrate MSCs as cellular targets of aGVHD and suggest a potential role of TNF-α blockage in maintaining the BM niche of aGVHD patients.
- Published
- 2020
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39. Clinical Features of COVID-19 Patients in Xiaogan City.
- Author
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Feng G, Huang WQ, Liu ML, Lin SC, Zhang XZ, Zhang Y, He XQ, Liu JL, Chen ZJ, Guo ZK, Gao J, Yao CZ, He N, Yan QQ, and Mi M
- Abstract
On February 6, 2020, Xiaogan City became the second most seriously affected city with coronavirus disease 2019 (COVID-19), outside Wuhan district, Hubei Province, China. The objectives are to study the clinical features of COVID-19 patients and assess the relationship between the severity of COVID-19, age, and C-reactive protein (CRP) levels. The retrospective data of 134 COVID-19 patients hospitalized in 3 hospitals of Xiaogan City, between February 1 and March 1, 2020, was collected. This study documented COVID-19 patients. Clinical data in terms of body temperature, history of travel, and direct contact with COVID-19 patients, and incubation period was collected. Out of the 134 patients, only 5 required intensive care. Moreover, 2 patients succumbed during this period. The median age of patients was 45 (33-56) years. The most common symptoms at the onset of disease were fever (66.4%), cough (33, 6%), and sore throat (14.7%). Amongst the medicines used, antiviral agents (92.3%) followed by the traditional Chinese medicine (89.5%) were most commonly used. In both the crude and adjusted (I to III) models, odds ratio and its 95% confidence interval for both age and CRP levels were > 1. Moreover, the smooth curve fitting graph reflected that the severity of COVID-19 was positively correlated with both age and CRP levels (all P value < 0.05). The signs and symptoms of COVID-19 patients were fairly moderate. The health care professionals treating the COVID-19 patients should be aware of the increased likelihood of progression to severe COVID-19 in elderly patients and those with high CRP levels., Competing Interests: Conflict of InterestThe authors declare that they have no conflicts of interest., (© Springer Nature Switzerland AG 2020.)
- Published
- 2020
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40. Hopf bifurcation of an age-structured HIV infection model with logistic target-cell growth.
- Author
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Guo ZK, Huo HF, and Xiang H
- Subjects
- Cell Proliferation, Computer Simulation, Humans, Numerical Analysis, Computer-Assisted, Algorithms, HIV Infections pathology, Models, Biological
- Abstract
In this paper, we investigate an age-structured HIV infection model with logistic growth for target cell. We rewrite the model as an abstract non-densely defined Cauchy problem and obtain the condition which guarantees the existence of the unique positive steady state. By linearizing the model at steady state and analysing the associated characteristic transcendental equations, we study the local asymptotic stability of the steady state. Furthermore, by using Hopf bifurcation theorem in Liu et al., we show that Hopf bifurcation occurs at the positive steady state when bifurcating parameter crosses some critical values. Finally, we perform some numerical simulations to illustrate our results.
- Published
- 2019
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41. [Effect of "Yinqi Guiyuan" needling on primary insomnia].
- Author
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Guan TX, Xu YF, Lin SJ, Qin XD, Li JF, Huang BQ, and Guo ZK
- Subjects
- Acupuncture Points, Humans, Sleep, Treatment Outcome, Acupuncture Therapy, Sleep Initiation and Maintenance Disorders therapy
- Abstract
Objective: To observe the clinical effect of "Yinqi Guiyuan" needling in the treatment of primary insomnia., Methods: A total of 79 primary insomnia outpatients were randomly divided into treatment group ( n =40) and control group ( n =39). The patients in the control group were given oral Estazolam tablets once a day, for successive 4 weeks. For patients of the treatment group, Zhongwan (CV12), Xiawan (CV10), Qihai (CV6), Guanyuan (CV4), Baihui (GV20), etc., were punctured with filiform needles for 30 min. The treatment was conducted three times per week for 4 successive weeks. The sleep quality (sleeping quality, falling asleep time, sleep duration, sleep efficiency, sleep disorders, hypnotic and daytime dysfunction, 0 to 21 points) was evaluated by using Pittsburgh Sleep Quality Index (PSQI). The severity of insomnia (self-perception, sleep satisfaction, daytime function damage, sensibility change, and concern for sleep problems, 0 to 28 points) was assessed using insomnia severity index (ISI) score. The therapeutic effect was evaluated according to the PSQI score reduction rate = (pre-treatment PSQI score-post-treatment PSQI score)/pre-treatment PSQI score ×100%., Results: After treatment, the total score of PSQI, ISI and the score of each item were all significantly reduced in the two groups relevant to their own pre-treatment ( P <0.05). The total score, and scores of hypnotic and daytime dysfunction were significantly lower in the treatment group than in the control group ( P <0.05). Of the 40 and 39 cases in the treatment and control groups, 5 (12.50%) and 4 (10.25%) were cured, 20 (50.00%) and 18 (46.15%) experienced marked improvement, 12 (30.00%) and 13 (33.33%) were effective, and 3 (7.50%) and 4 (10.25%) ineffective, with the total effective rate being 92.50% and 89.74%, respectively. No significant difference was found between the two groups in the effective rate ( P >0.05)., Conclusion: "Yinqi Guiyuan" needling and Estazolam are comparable in treatment primary insomnia, and the former is superior to the latter in avoiding hypnotic drug use and in improving daytime function.
- Published
- 2019
- Full Text
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42. A new flavonoid derivative and a new 5-hydroxyanthranilic acid derivative from the sea urchin-derived Streptomyces sp. HDa1.
- Author
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Guo ZK, Wang R, Liu TM, Chen FX, and Yang MQ
- Subjects
- Animals, Anti-Bacterial Agents isolation & purification, Anti-Bacterial Agents pharmacology, Bacteria drug effects, Magnetic Resonance Spectroscopy, Microbial Sensitivity Tests, Molecular Structure, Spectrometry, Mass, Electrospray Ionization, Flavonoids isolation & purification, Flavonoids pharmacology, Sea Urchins microbiology, Streptomyces chemistry
- Abstract
One new flavonoid derivative flavoside A ( 1 ), one new 5-hydroxyanthranilic acid derivative crassilin ( 2 ), along with the known angucyclinone PD116740 ( 3 ) and oxachelin ( 4 ), was isolated from the EtOAc extract of the fermentation broth of the sea urchin ( Anthocidaris crassispina )-derived actinobacterium, Streptomyces sp. HD01. The structures of these compounds were established on the basis of their HR-ESI-MS and NMR spectroscopic data. All of these compounds were assessed for their antibacterial activity.
- Published
- 2019
- Full Text
- View/download PDF
43. Bioactive phenazines from an earwig-associated Streptomyces sp.
- Author
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Han H, Guo ZK, Zhang B, Zhang M, Shi J, Li W, Jiao RH, Tan RX, and Ge HM
- Subjects
- Animals, Anti-Bacterial Agents metabolism, Anti-Bacterial Agents pharmacology, Bacterial Proteins genetics, Bacterial Proteins metabolism, Crystallography, X-Ray, Magnetic Resonance Spectroscopy, Microbial Sensitivity Tests, Micrococcus luteus drug effects, Molecular Structure, Multigene Family, Phenazines metabolism, Phenazines pharmacology, Streptomyces genetics, Streptomyces metabolism, Anti-Bacterial Agents chemistry, Insecta microbiology, Phenazines chemistry, Streptomyces chemistry
- Abstract
Three new phenazine-type compounds, named phenazines SA-SC (1-3), together with four new natural products (4-7), were isolated from the fermentation broth of an earwig-associated Streptomyces sp. NA04227. The structures of these compounds were determined by extensive analyses of NMR, high resolution mass spectroscopic data, as well as single-crystal X-ray diffraction measurement. Sequencing and analysis of the genome data allowed us to identify the gene cluster (spz) and propose a biosynthetic pathway for these phenazine-type compounds. Additionally, compounds 1-5 exhibited moderate inhibitory activity against acetylcholinesterase (AChE), and compound 3 showed antimicrobial activities against Micrococcus luteus., (Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
44. Bialternacins A-F, Aromatic Polyketide Dimers from an Endophytic Alternaria sp.
- Author
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Yang CL, Wu HM, Liu CL, Zhang X, Guo ZK, Chen Y, Liu F, Liang Y, Jiao RH, Tan RX, and Ge HM
- Subjects
- Acetylcholinesterase drug effects, Cholinesterase Inhibitors chemistry, Cholinesterase Inhibitors isolation & purification, Cholinesterase Inhibitors pharmacology, Crystallography, X-Ray, Dimerization, Molecular Structure, Plant Leaves chemistry, Polyketides chemistry, Polyketides pharmacology, Spectrum Analysis methods, Alternaria chemistry, Polyketides isolation & purification
- Abstract
Six novel aromatic polyketide dimers, bialternacins A-F (1-6), were isolated from a plant endophytic Alternaria sp. The structures of compounds 1-6 were elucidated on the basis of extensive spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism analysis. Compounds 1, 2, 5, and 6 were characterized as four pairs of racemic mixtures. Compound (+)-5 was demonstrated to show acetylcholinesterase inhibitory activity with an IC
50 value of 15.5 μM. A putative biosynthetic pathway for these compounds was proposed.- Published
- 2019
- Full Text
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45. Evaluation of Potato virus X mild mutants for cross protection against severe infection in China.
- Author
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Cong QQ, Wang Y, Liu J, Lan YF, Guo ZK, Yang JG, Li XD, and Tian YP
- Subjects
- China, Genome, Viral, Solanum lycopersicum virology, Mutagenesis, Site-Directed, Plant Leaves virology, Potexvirus enzymology, Potexvirus physiology, RNA, Viral genetics, RNA-Dependent RNA Polymerase genetics, Reverse Genetics, Nicotiana virology, Viral Proteins genetics, Virulence genetics, Cross Protection, Mutation, Plant Diseases virology, Potexvirus genetics
- Abstract
Background: Cross protection is a promising alternative to control plant viral diseases. One critical factor limiting the application of cross protection is the availability of attenuated mutants or mild strains. Potato virus X (PVX) infects many crops and induces huge economic losses to agricultural production. However, researches on the variability and mechanism of PVX virulence are scarce., Methods: The mutants were obtained by introducing mutations into the RNA dependent RNA polymerase (RdRp) gene of PVX via site-directed mutagenesis. Attenuated mutants were screen according to their symptoms in Nicotiana benthamiana plants. The protection efficacy against severe infection were evaluated with interval of 5, 10 and 15 days., Results: Among the 40 mutants obtained, four mutants carrying substitutions of either Glu
46 , Asn863 , Asn968 or Glu1001 to Ala in PVX RdRp showed drastically attenuated symptom, accompanying with reduced accumulation levels of coat protein, plus- and minus-sense RNAs. When the interval between protective and challenging inoculations was 15 days, mutant E1001A (with substitution of Glu1001 to Ala in RdRp) provided complete protection against severe infection in both Nicotiana benthamiana and tomato, while E46A (Glu46 mutated to Ala) provided incomplete protection. To reduce the risk of reverse mutation, we constructed mutant dM which carries double mutations of both Glu46 and Glu1001 to Ala in RdRp. The mutant dM could provide effective protection against severe PVX infection., Conclusion: Mutations of Glu46 , Asn863 , Asn968 or Glu1001 to Ala in PVX RdRp significantly reduced the viral symptoms. Mutants E1001A and E46A could provide effective protection against wild type PVX in both Nicotiana benthamiana and tomato. These results provide theoretical and practical bases for the control of PVX via cross protection.- Published
- 2019
- Full Text
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46. Global dynamics of an age-structured malaria model with prevention.
- Author
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Guo ZK, Huo HF, and Xiang H
- Subjects
- Animals, Computer Simulation, Culicidae, Female, Global Health, Humans, Infectious Disease Medicine methods, Malaria parasitology, Models, Biological, Public Health, Basic Reproduction Number, Communicable Disease Control methods, Malaria prevention & control, Malaria transmission
- Abstract
In this paper, we formulate a new age-structured malaria model, which incorporates the age of prevention period of susceptible people, the age of latent period of human and the age of latent period of female Anopheles mosquitoes. We show that there exists a compact global attractor and obtain a sufficient condition for uniform persistence of the solution semiflow. We obtain the basic reproduction number R₀ and show that R₀ completely determines the global dynamics of the model, that is, if R₀ < 1, the disease-free equilibrium is globally asymptotically stable, if R₀ > 1, there exists a unique endemic equilibrium that attracts all solutions for which malaria transmission occurs. Finally, we perform some numerical simulations to illustrate our theoretical results and give a brief discussion.
- Published
- 2019
- Full Text
- View/download PDF
47. A new insecticidal havanensin-type limonoid from the roots of Trichilia sinensis Bentv.
- Author
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Liu SB, Chen HQ, Feng G, Guo ZK, Cai CH, Wang J, Mei WL, and Dai HF
- Subjects
- Animals, Insecticides chemistry, Insecticides pharmacology, Larva drug effects, Limonins chemistry, Limonins isolation & purification, Limonins pharmacology, Magnetic Resonance Spectroscopy, Molecular Structure, Plant Roots chemistry, Spectrum Analysis, Spodoptera drug effects, Insecticides isolation & purification, Meliaceae chemistry
- Abstract
One new havanensin-type limonoid ( 1 ) named trisinlin A with two known compounds (4 E ,8 E )-2-[2'-hydroxyhexadecanoyl amino]-4,8-octadecadiene-1,3-diol ( 2 ), 9-octadecenoic acid-2',3'-dihydroxypropyl ester ( 3 ) were isolated from the roots of Trichilia sinensis . The structure of the new compound was unambiguously determined through comprehensive spectroscopic analyses including 1D and 2D NMR, and mass spectrometry, as well as by comparison with the literature. Trisinlin A showed significant insecticidal activity against newly hatched larvae of Spodoptera litura .
- Published
- 2018
- Full Text
- View/download PDF
48. Bifurcation analysis of an age-structured alcoholism model.
- Author
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Guo ZK, Huo HF, and Xiang H
- Subjects
- Age Factors, Computer Simulation, Humans, Numerical Analysis, Computer-Assisted, Alcoholism epidemiology, Models, Biological
- Abstract
In this paper, we investigate a new alcoholism model in which alcoholics have age structure. We rewrite the model as an abstract non-densely defined Cauchy problem and obtain the condition which guarantees the existence of the unique positive steady state. By linearizing the model at steady state and analyzing the associated characteristic transcendental equations, we study the local asymptotic stability of the steady state. Furthermore, by using Hopf bifurcation theorem in Liu et al. (Z. Angew. Math. Phys. 62 (2011) 191-222), we show that Hopf bifurcation occurs at the positive steady state when bifurcating parameter crosses some critical values. Finally, we perform some numerical simulations to illustrate our theoretical results and give a brief conclusion.
- Published
- 2018
- Full Text
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49. [Effect of TGF-β1 and IL-10 on the Immunoregulatory Function of Extracellular Vesicles Derived from Mesenchymal Stem Cells].
- Author
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Ma C, Zang QY, Guo ZK, and Wang HX
- Subjects
- Extracellular Vesicles, Humans, Interleukin-10, Leukocytes, Mononuclear, Transforming Growth Factor beta1, Mesenchymal Stem Cells
- Abstract
Objective: To investigate the effect of immune regulatory molecules TGF-β1 and IL-10 on the immunoregulatory activities of extracellular vesicles(EV) secreted from mesenchymal stem cells (MSCs)., Methods: MSC were isolated from human umbilical cord and expanded, then were treated with TGF-β1 and IL-10 for 72h, and MSC-EVs in supernatants were isolated. The total protein content of all samples was determined by BCA methed. The morphological structure was observed by transmission electron microscopy. The surface markers of MSC-EV were analyzed by flow cytometry. The apoptosis of peripheral blood mononuclear cells(PBMNC) stimulated by ConA and the proportion of CD4
+ CD25+ /CD127- (Treg) cells were detected by flow cytometry after incubation with MSC-EV for 72 h. The CBA and ELISA kit were used to detect the contents of IL2, IL4, IL6, IL10, IFN-γ, TNF-α, Th17A and TGF-β1 in PBMC supernatants and MSC-EV., Results: All the samples showed that the typical cup-shaped membrane-like structure was observed by transmission electron microscopy, and CD9, CD44, CD63 and CD81 expressed. After TGF-β1 treatment, the MSC-EV displayed the strongest ability to promote PBMNC apoptosis(P<0.01), and in all the samples the proportion of Treg cells increased. MSC-EV could increase the content of IL-10 in the supernatants of PBMNC culture, the content of TGF-β1 in PBMNC supernatants after MSC treatment with TGF-β1 was lower than that in untreated group(P<0.05). The content of IL-6 in MSC-EV increased significantly after treatment with TGF-β1, and the content of TGF-β1 decreased., Conclusion: TGF-β1 alters the immnomodulatory function of MSC-EV and its underlying mechanisms need to be clarified in further investigations.- Published
- 2018
- Full Text
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50. Streptoxamine, an unprecedented benzoisoindole-deferoxamine hybrid from the locust-derived Streptomyces sp. HKHCa2.
- Author
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Guo ZK, Wang R, Chen FX, and Liu TM
- Subjects
- Animals, Anti-Bacterial Agents pharmacology, Deferoxamine pharmacology, Fermentation, Indoles pharmacology, Microbial Sensitivity Tests, Molecular Structure, Mycobacterium smegmatis drug effects, Staphylococcus aureus drug effects, Anti-Bacterial Agents isolation & purification, Deferoxamine isolation & purification, Grasshoppers microbiology, Indoles isolation & purification, Streptomyces chemistry
- Abstract
An unusual benzoisoindole-deferoxamine hybrid, streptoxamine (1), has been isolated from the ethyl acetate crude extract of the fermentation broth of a locust-associated actinomycete, Streptomyces sp. HKHCa2, which was isolated from an insect, Oxya chinensis. The structure of this secondary metabolite was elucidated on the basis of its one-dimension, two-dimension NMR, and mass spectroscopic data. This natural product features a hybrid pattern of a benzoisoindole with an "iron carrier" deferoxamine B through C-N linkage. Compound 1 showed weak antibacterial activity against the gram-positive bacteria, Staphylococcus aureus and Mycobacterium smegmatis., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
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