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| 1 | Efficacy of cattle encephalon glycoside and ignotin in patients with acute cerebral infarction: a randomized, double-blind, parallel-group, placebo-controlled study显示文摘Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries.However,there is still a need for high-level clinical evidence from large samples to support the use of CEGI.We therefore carried out a prospective,multicenter,randomized,double-blind,parallel-group,placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016.The patients were randomized at a 3:1 ratio into CEGI(n=239;155 male,84 female;61.2±9.2 years old)and placebo(n=80;46 male,34 female;63.2±8.28 years old)groups.All patients were given standard care once daily for 14 days,including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium,both taken orally,and intravenous infusion of 250–500 mL 0.9%sodium chloride containing 40 mg sodium tanshinone IIA sulfonate.Based on conventional treatment,patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water,respectively,in an intravenous drip of 250 mL 0.9%sodium chloride(2 mL/min)once daily for 14 days.According to baseline National Institutes of Health Stroke Scale scores,patients in the two groups were divided into mild and moderate subgroups.Based on the modified Rankin Scale results,the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group,and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment.In the CEGI group,neurological deficits were decreased on days 14 and 90 after treatment,as measured by the National Institutes of Health Stroke Scale and the Barthel Index.Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients.No drug-related adverse events occurred in the CEGI or placebo groups.In conclusion,CEGI may be a safe and effective treatment for acute cerebral infarction patients,especially for moderate stroke patients.This study was approved by the Ethical Committee of Peking University Third Hospital,China(approval No.2013-068-2)on May 20,2013,and registered in the Chinese Clinical Trial Registry(registration No.ChiCTR1800017937). | Hui Zhang Chuan-Ling Li Feng Wan Su-Juan Wang Xiu-E Wei Yan-Lei Hao Hui-Lin Leng Jia-Min Li Zhong-Rui Yan Bao-Jun Wang Ren-Shi Xu Ting-Min Yu Li-Chun Zhou Dong-Sheng Fan | 2020 | Neural Regeneration Research2020，15，7： | 54 |
| 2 | Direct Yaw Moment Control for Distributed Drive Electric Vehicle Handling Performance Improvement显示文摘For a distributed drive electric vehicle(DDEV) driven by four in-wheel motors, advanced vehicle dynamic control methods can be realized easily because motors can be controlled independently, quickly and precisely. And direct yaw-moment control(DYC) has been widely studied and applied to vehicle stability control. Good vehicle handling performance: quick yaw rate transient response, small overshoot, high steady yaw rate gain, etc, is required by drivers under normal conditions, which is less concerned, however. Based on the hierarchical control methodology, a novel control system using direct yaw moment control for improving handling performance of a distributed drive electric vehicle especially under normal driving conditions has been proposed. The upper-loop control system consists of two parts: a state feedback controller, which aims to realize the ideal transient response of yaw rate, with a vehicle sideslip angle observer; and a steering wheel angle feedforward controller designed to achieve a desired yaw rate steady gain. Under the restriction of the effect of poles and zeros in the closed-loop transfer function on the system response and the capacity of in-wheel motors, the integrated time and absolute error(ITAE) function is utilized as the cost function in the optimal control to calculate the ideal eigen frequency and damper coefficient of the system and obtain optimal feedback matrix and feedforward matrix. Simulations and experiments with a DDEV under multiple maneuvers are carried out and show the effectiveness of the proposed method: yaw rate rising time is reduced, steady yaw rate gain is increased, vehicle steering characteristic is close to neutral steer and drivers burdens are also reduced. The control system improves vehicle handling performance under normal conditions in both transient and steady response. State feedback control instead of model following control is introduced in the control system so that the sense of control intervention to drivers is relieved. | YU Zhuoping LENG Bo XIONG Lu FENG Yuan SHI Fenmiao | 2016 | Chinese Journal of Mechanical Engineering2016，29，3： | 28 |
| 3 | Water regime-nitrogen fertilizer incorporation interaction:Field study on methane and nitrous oxide emissions from a rice agroecosystem in Harbin, China显示文摘Water regime and nitrogen(N) fertilizer are two important factors impacting greenhouse gases(GHG) emission from paddy field, whereas their effects have not been well studied in cold region. In this study, we conducted a two-year field experiment to study the impacts of water regime and N fertilizer on rice yields and GHG emissions in Harbin, China, a cold region located in high latitudes. Our results showed that intermittent irrigation significantly decreased methane(CH_4) emission compared with continuous flooding, however,the decrement was far lower than the global average level. The N_2O emissions were very small when flooded but peaked at the beginning of the disappearance of floodwater. The N fertilizer treatments increased CH_4 emissions at low level(75 kg N/ha). But both CH_4 and N_2O emissions were uninfluenced at the levels of 150 kg N/ha and 225 kg N/ha. Rice yields increased under intermittent irrigation and were highest at the level of 150 kg N/ha. From our results, we recommended that the intermittent irrigation and 150 kg N/ha as the ideal water regime-nitrogen fertilizer incorporation for this area to achieve low GHG emissions without impacting rice yields. | Wenjun Dong Jia Guo Lijun Xu Zhifeng Song Jun Zhang Ao Tang Xijuan Zhang Chunxu Leng Youhong Liu Lianmin Wang Lizhi Wang Yang Yu Zhongliang Yang Yilei Yu Ying Meng Yongcai Lai | 2018 | Journal of Environmental Sciences2018，30，2： | 12 |
| 4 | Fundamental mechanisms and phenomena of clathrate hydrate nucleation显示文摘Insights into the mechanism of hydrate nucleation are of great significance for the development of hydrate-based technologies,hydrate relevant flow assurance,and the exploration of in situ natural gas hydrates.Compared with the thermodynamics of hydrate formation,understanding the nucleation mechanism is challenging and has drawn substantial attention in recent decades.In this paper,we attempt to give a comprehensive review of the recent progress of studies of clathrate hydrate nucleation.First,the existing hypotheses on the hydrate nucleation mechanism are introduced and discussed.Then,we summarize recent experimental studies on induction time,a key parameter evaluating the velocity of the nucleation process.Subsequently,the memory effect is particularly discussed,followed by the suggestion of several promising research perspectives. | Jinlong Cui Zhenfeng Sun Xiaohui Wang Bin Yu Shudong Leng Guangjin Chen Changyu Sun | 2019 | Chinese Journal of Chemical Engineering2019，27，9： | 11 |
| 5 | LSD1 coordinates with the SIN3A/HDAC complex and maintains sensitivity to chemotherapy in breast cancer显示文摘 | Yang Yang Wei Huang Rongfang Qiu Ruiqiong Liu Yi Zeng Jie Gao Yu Zheng Yongqiang Hou Shuang Wang Wenqian Yu Shuai Leng Dandan Feng Yan Wang | 2018 | Journal of Molecular Cell Biology2018，10，4： | 10 |
| 6 | Hypoxia increases adipogenesis and affects adipocytokine production in orbital fibroblasts-a possible explanation of the link between smoking and Graves' ophthalmopathy显示文摘AIM:To assess the effects of hypoxia on human orbital fibroblasts(OF)on adipogenesis and adipocytokine production.METHODS:Human OF were derived from tissues obtained from patients with Graves'ophthalmopathy(GO)and from patients without known thyroid diseases undergoing blepharoplasty.The OF were cultured separately under normoxic and hypoxic conditions.Comparisons of adipocytokine concentrations using multiplex ELISA and lipid accumulation in the cells using Oil Red O staining were subsequently performed.RESULTS:There was increased adipogenesis in OF from GO subject when exposed to hypoxic culture conditions.This was not observed in OF from normal controls.Hypoxia led to an increase in leptin and a decrease in MCP-1 secretion in OF cultures.CONCLUSION:Hypoxia induces adipogenesis in OF and may represent a mechanism by which smoking contributes to deterioration of GO.We also found novel changes to leptin and MCP-1 production in OF cultures exposed to hypoxia suggesting important roles of these cytokines in the disease process. | Chiaw Ling Chng Oi Fah Lai Charmaine Sze-Min Chew Yu Pei Peh Stephanie Man-Chung Fook-Chong Lay Leng Seah Daphne Hsu-Chin Khoo | 2014 | International Journal of Ophthalmology(English edition)2014，7，3： | 10 |
| 7 | Three-dimensional-printed individualized porous implants:A new“implant-bone”interface fusion concept for large bone defect treatment显示文摘Bone defect repairs are based on bone graft fusion or replacement.Current large bone defect treatments are inadequate and lack of reliable technology.Therefore,we aimed to investigate a simple technique using three-dimensional(3D)-printed individualized porous implants without any bone grafts,osteoinductive agents,or surface biofunctionalization to treat large bone defects,and systematically study its long-term therapeutic effects and osseointegration characteristics.Twenty-six patients with large bone defects caused by tumor,infection,or trauma received treatment with individualized porous implants;among them,three typical cases underwent a detailed study.Additionally,a large segmental femur defect sheep model was used to study the osseointegration characteristics.Immediate and long-term biomechanical stability was achieved,and the animal study revealed that the bone grew into the pores with gradual remodeling,resulting in a long-term mechanically stable implant-bone complex.Advantages of 3D-printed microporous implants for the repair of bone defects included 1)that the stabilization devices were immediately designed and constructed to achieve early postoperative mobility,and 2)that osseointegration between the host bone and implants was achieved without bone grafting.Our osseointegration method,in which the“implant-bone”interface fusion concept was used instead of“bone-bone”fusion,subverts the traditional idea of osseointegration. | Teng Zhang Qingguang Wei Hua Zhou Zehao Jing Xiaoguang Liu Yufeng Zheng Hong Cai Feng Wei Liang Jiang Miao Yu Yan Cheng Daoyang Fan Wenhao Zhou Xinhong Lin Huijie Leng Jian Li Xinyu Li Caimei Wang Yun Tian Zhongjun Liu | 2021 | Bioactive Materials2021，6，11： | 9 |
| 8 | The status of exploitation techniques of natural gas hydrate显示文摘Natural gas hydrate(NGH)has been widely considered as an alternative form of energy with huge potential,due to its tremendous reserves,cleanness and high energy density.Several countries involving Japan,Canada,India and China have launched national projects on the exploration and exploitation of gas hydrate resources.At the beginning of this century,an early trial production of hydrate resources was carried out in Mallik permafrost region,Canada.Japan has conducted the first field test from marine hydrates in 2013,followed by another trial in 2017.China also made its first trial production from marine hydrate sediments in 2017.Yet the low production efficiency,ice/hydrate regeneration,and sand problems are still commonly encountered;the worldwide progress is far before commercialization.Up to now,many gas production techniques have been proposed,and a few of them have been adopted in the field production tests.Nevertheless,hardly any method appears really promising;each of them shows limitations at certain conditions.Therefore,further efforts should be made on the economic efficiency as well as sustainability and environmental impacts.In this paper,the investigations on NGH exploitation techniques are comprehensively reviewed,involving depressurization,thermal stimulation,chemical inhibitor injection,CO2–CH4 exchange,their combinations,and some novel techniques.The behavior of each method and its further potential in the field test are discussed.The advantages and limitations of laboratory studies are also analyzed.The work could give some guidance in the future formulation of exploitation scheme and evaluation of gas production behavior from hydrate reservoirs. | Lei Yang Yulong Liu Hanquan Zhang Bo Xiao Xianwei Guo Rupeng Wei Lei Xu Lingjie Sun Bin Yu Shudong Leng Yanghui Li | 2019 | Chinese Journal of Chemical Engineering2019，27，9： | 9 |
| 9 | Sustainable Practice in Pavement Engineering through Value-Added Collective Recycling of Waste Plastic and Waste Tyre Rubber显示文摘Waste plastics,such as waste polyethylene terephthalate(PET)beverage bottles and waste rubber tyres are major municipal solid wastes,which may lead to various environmental problems if they are not appropriately recycled.In this study,the feasibility of collectively recycling the two types of waste into performance-increasing modifiers for asphalt pavements was analyzed.This study aimed to investigate the recycling mechanisms of waste PET-derived additives under the treatment of two amines,triethylenetetramine(TETA)and ethanolamine(EA),and characterize the performances of these additives in modifying rubberized bitumen,a bitumen modified by waste tyre rubber.To this end,infrared spectroscopy and thermal analyses were carried out on the two PET-derived additives(PET–TETA and PET–EA).In addition,infrared spectroscopy,viscosity,dynamic shear rheology,and multiple stress creep recovery tests were performed on the rubberized bitumen samples modified by the two PET-derived additives.We concluded that waste PET can be chemically upcycled into functional additives,which can increase the overall performance of the rubberized bitumen.The recycling method developed in this study not only helps alleviate the landfilling problems of both waste PET plastic and scrap tyres,but also turns these wastes into value-added new materials for building durable pavements. | Xiong Xu Zhen Leng Jingting Lan Wei Wang Jiangmiao Yu Yawei Bai Anand Sreeram Jing Hu | 2021 | Engineering2021，7，6： | 7 |
| 10 | Selective Synthesis of Hexagonal Ag Nanoplates in a Solution-Phase Chemical Reduction Process显示文摘Two-dimensional(2-D)Ag nanoplates have surface plasmon resonances which can be tuned from the visible to the near-IR by varying the size and morphology of the nanoplates.Due to their anisotropic structures and different surface energy distributions,Ag nanoplates-especially triangular ones-are kinetically stable and can transform into other nanostructures.Taking advantage of the synergetic effects of HNO_(3)and Cl-in the reduction solution,uniform Ag hexagonal nanoplates(HNPs)have been captured during the transformation of Ag triangular nanoplates(TNPs).The dimensions of the Ag HNPs can be controlled by changing the concentrations of reagents in the reaction or/and reduction solutions.Resonance absorption spectra of the obtained Ag HNPs indicated that their in-plane resonance peaks could be tuned from the visible to the near-IR region,showing their potential applications in medical diagnosis. | Mingzhu Liu Mei Leng Chao Yu Xin Wang Cheng Wang | 2010 | Nano Research2010，3，12： | 5 |
| 11 | Protective effects of MCI-186 on oxidative damage in a cell model of Alzheimer's disease显示文摘Oxidative stress has an important role in the development of Alzheimer's disease (AD). Beta amyloid protein 25-35 (Aβ25-35) can generate oxygen free radicals, and MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one, edaravone) can specifically eliminate hydroxyl radicals. The present study introduced Aβ25-35 into PC12 cells to establish a cell model of AD, and investigated the neuroprotective effects of MCI-186 on AD. Results showed that MCI-186 had a positive effect on the prevention and treatment of AD by inhibiting protein oxidative products, advanced glycation end products, lipid oxidative end products and DNA oxidative damage in PC12 cells induced by Aβ25-35. | Ming Yu Shujuan Li Wenhui Leng Han Chen Yingquan Wu Lirong Yan | 2010 | Neural Regeneration Research2010，5，16： | 5 |
| 12 | Prediction of Cerebral Hyperperfusion Syndrome with Velocity Blood Pressure Index显示文摘 | Zhi-Chao Lai Bao Liu Yu Chen Leng Ni Chang-Wei Liu | 2015 | Chinese Medical Journal2015，，12： | 4 |
| 13 | Antidiabetic effect of a novel non-thiazolidinedione PPAR γ/α agonist on ob/ob mice显示文摘Aim:To study whether T33,a new synthesized non-thiazolidinedione(TZD)per-oxisome proliferator-activated receptor(PPAR)γ/α dual agonist has an antidia-betic effect on ob/ob mice.Methods:Ob/ob mice were treated with 4 mg/kg or 8mg/kg T33 by gavage for 20 d.Blood glucose levels were measured regularly.Anoral glucose tolerance test(OGTT)and an insulin tolerance test(ITT)were pre-formed on d 8 and d 12,respectively.The levels of insulin,triglyceride and freefatty acid(FFA)in the serum were measured at the end of administration.Theintramuscular and liver triglyceride content was also determined.Results:T33reduced the hyperglycemia,hyperinsulinemia and hyperlipidemia of the ob/obmice.The OGTT and ITT showed that the insulin resistance state of the ob/obmice was obviously ameliorated after T33 treatment.After 20 d treatment with 8mg/kg T33,the triglyceride content in the gastrocnemius muscle decreasedsignificantly.T33 did not have any effect on triglyceride content in the liver,whereas rosiglitazone significantly increased the hepatocyte lipid deposition.Conclusion:The PPARγ/α dual agonist T33 has antidiabetic and insulin-sensitiz-ing effects in ob/ob mice.It has the potential to be a new therapeutic candidate forthe treatment of type 2 diabetes. | Xi HU Ying FENG Yu SHEN Xiao-feng ZHAO Juan-hong YU Yu-she YANG Ying LENG | 2006 | Acta Pharmacologica Sinica2006，27，10： | 4 |
| 14 | Retrospective analysis of interventional treatment of hepatic metastasis from gastroenteropancreatic neuroendocrine tumors显示文摘Objective: To analyze the angiography appearance of liver metastases from gastroenteropancreatic neuroendocrine tumors(GEP-NETs),and evaluate the clinical efficacy and prognostic factors of interventional treatment for hepatic metastases.Methods: Fifty GEP-NETs patients with hepatic metastases were treated from January 2012 to December 2016,and received transarterial embolization(TAE) in the hepatic tumor or hepatic arterial infusion chemotherapy(HAIC).All patients received 179 times of the intervention therapy in total.Results: Blood supplies were identified in the 50 cases with angiography,which showed that 35 cases had abundant vessels,while 15 cases had poor blood supply.Twenty-two cases were found either collateral blood supply,or portal vein invasion or arterial-portal vein fistula.The best curative efficacy was complete remission(CR)in 4 cases,partial remission(PR) in 28 cases and stable disease(SD) in 18 cases during the process of treatment.The angiography(P=0.047) and the frequency of intervention(P=0.037) showed significantly statistical difference with Kaplan-Meier analysis.The Cox analysis showed that more than 3 times of interventional therapy was an independent prognostic factor.Conclusions: Interventional treatment is safe and effective for GEP-NETs,and is beneficial to patients with main hepatic metastases after endocrine therapy. | Peng Liu Xu Zhu Jie Li Ming Lu Jiahua Leng Ying Li Jiangyuan Yu | 2017 | Chinese Journal of Cancer Research2017，29，6： | 4 |
| 15 | The pleiotropic ABNORMAL FLOWER AND DWARF1 affects plant height, floral development and grain yield in rice显示文摘Moderate plant height and successful establishment of reproductive organs play pivotal roles in rice grain production. The molecular mechanism that controls the two aspects remains unclear in rice. In the present study,we characterized a rice gene, ABNORMAL FLOWER AND DWARF1(AFD1) that determined plant height, floral development and grain yield. The afd1 mutant showed variable defects including the dwarfism, long panicle, low seed setting and reduced grain yield. In addition, abnormal floral organs were also observed in the afd1 mutant including slender and thick hulls, and hull-like lodicules.AFD1 encoded a DUF640 domain protein and was expressed in all tested tissues and organs. Subcellular localization showed AFD1-green fluorescent fusion protein(GFP) was localized in the nucleus. Meantime, our results suggested that AFD1 regulated the expression of cell division and expansion related genes. | Deyong Ren Yuchun Rao Liwen Wu Qiankun Xu Zizhuang Li Haiping Yu Yu Zhang Yujia Leng Jiang Hu Li Zhu Zhenyu Gao Guojun Dong Guangheng Zhang Longbiao Guo Dali Zeng Qian Qian | 2016 | Journal of Integrative Plant Biology2016，58，6： | 4 |
| 16 | Remodeling of skin nerve fibers during burn wound healing显示文摘Burn wound healing involves a complex sequence of processes.Recent studies have revealed that skin reinnervation may have an impact on physiological wound repair.Few studies have addressed the process of reinnervation and morphological changes in regenerated nerve fibers.The regeneration of neurites during full-thickness burn wound healing was determined by immunofluorescent staining using an anti-neurofilament protein monoclonal antibody,and three-dimensional morphology was observed under a laser scanning confocal microscope.Morphology and the volume fraction of collagen and nerve fibers were measured.Skin reinnervation increased during wound healing,peaked during the proliferative scar stage,and then decreased to lower levels during the maturation period.The results from the skin nerve fibers correlated with those from collagen using semi-quantitative analysis.Disintegration and fragmentation were observed frequently in samples from the proliferative stage,and seldom occurred during the maturation stage.There was a remodeling process of regenerated nerve fibers during wound healing,which comprised changed innervation density and topical morphology.The mechanism of remodeling for nerve fibers requires further investigation. | Yongqiang Feng Xia Li Rui Zhang Yu Liu Tingting Leng Yibing Wang | 2010 | Neural Regeneration Research2010，5，19： | 4 |
| 17 | Cytogenetic and molecular aberrations of multiple myeloma patients: a single-center study in Singapore显示文摘 | LIM Alvin Soon Tiong LIM Tse Hui SEE Karen Hsu Shien NG Yit Jun TAN Yu Min CHO0 Natasha Swee Lian LIM Sherry Xin Er YEE Yenny LAU Lai Ching TIEN Sim Leng Kumar Sathish TAN Daryl Chen Lung | 2013 | Chinese Medical Journal2013，，10： | 4 |
| 18 | Glucocorticoid receptor modulates myeloid-derived suppressor cell function via mitochondrial metabolism in immune thrombocytopenia显示文摘Myeloid-derived suppressor cells(MDSCs)are a heterogeneous population of immature cells and natural inhibitors of adaptive immunity.Intracellular metabolic changes in MDSCs exert a direct immunological influence on their suppressive activity.Our previous study demonstrated that high-dose dexamethasone(HD-DXM)corrected the functional impairment of MDSCs in immune thrombocytopenia(ITP);however,the MDSC population was not restored in nonresponders,and the mechanism remained unclear.In this study,altered mitochondrial physiology and reduced mitochondrial gene transcription were detected in MDSCs from HD-DXM nonresponders,accompanied by decreased levels of carnitine palmitoyltransferase-1(CPT-1),a rate-limiting enzyme in fatty acid oxidation(FAO).Blockade of FAO with a CPT-1 inhibitor abolished the immunosuppressive function of MDSCs in HD-DXM responders.We also report that MDSCs from ITP patients had lower expression of the glucocorticoid receptor(GR),which can translocate into mitochondria to regulate the transcription of mitochondrial DNA(mtDNA)as well as the level of oxidative phosphorylation.It was confirmed that the expression of CPT-1 and mtDNA-encoded genes was downregulated in GR-siRNA-treated murine MDSCs.Finally,by establishing murine models of active and passive ITP via adoptive transfer of DXM-modulated MDSCs,we confirmed that GR-silenced MDSCs failed to alleviate thrombocytopenia in mice with ITP.In conclusion,our study indicated that impaired aerobic metabolism in MDSCs participates in the pathogenesis of glucocorticoid resistance in ITP and that intact control of MDSC metabolism by GR contributes to the homeostatic regulation of immunosuppressive cell function. | Yu Hou Jie Xie Shuwen Wang Daqi Li Lingjun Wang Haoyi Wang Xiaofei Ni Shaoqiu Leng Guosheng Li Ming Hou Jun Peng | 2022 | Cellular & Molecular Immunology2022，19，7： | 4 |
| 19 | Design and measurement of signal processing system for cavity beam position monitor显示文摘In this paper,in order to achieve the output signal processing of cavity beam position monitor(CBPM),we develop a digital intermediate frequency receiver architecture based signal processing system,which consists of radio frequency(RF) front end and high speed data acquisition board.The beam position resolution in the CBPM signal processing system is superior to 1μm.Two signal processing algorithms,fast Fourier transform(FFT) and digital down converter(DDC),are evaluated offline using MATLAB platform,and both can be used to achieve,the CW input signal,position resolutions of 0.31μm and 0.10μm at -16 dBm.The DDC algorithm for its good compatibility is downloaded into the FPGA to realize online measurement,reaching the position resolution of 0.49μm due to truncation error.The whole system works well and the performance meets design target. | WANG Baopeng LENG Yongbin YU Luyang ZHOU Weimin YUAN Renxian CHEN Zhichu | 2013 | Nuclear Science and Techniques2013，24，2： | 3 |
| 20 | Functional characterization and key residues engineering of a regiopromiscuity O-methyltransferase involved in benzylisoquinoline alkaloid biosynthesis in Nelumbo nucifera显示文摘Lotus(Nelumbo nucifera),an ancient aquatic plant,possesses a unique pharmacological activity that is primarily contributed by benzylisoquinoline alkaloids(BIAs).However,only few genes and enzymes involved in BIA biosynthesis in N.nucifera have been isolated and characterized.In the present study we identified the regiopromiscuity of an O-methyltransferase,designated NnOMT6,isolated from N.nucifera;NnOMT6 was found to catalyze the methylation of monobenzylisoquinoline 6-O/7-O,aporphine skeleton 6-O,phenylpropanoid 3-O,and protoberberine 2-O.We further probed the key residues affecting NnOMT6 activity via molecular docking and molecular dynamics simulation.Verification using site-directed mutagenesis revealed that residues D316,N130,L135,N176A,D269,and E328 were critical for BIA O-methyltransferase activities;furthermore,N323A,a mutant of NnOMT6,demonstrated a substantial increase in catalytic efficiency for BIAs and a broader acceptor scope compared with wild-type NnOMT6.To the best of our knowledge,this is the first study to report the O-methyltransferase activity of an aporphine skeleton without benzyl moiety substitutions in N.nucifera.The study findings provide biocatalysts for the semisynthesis of related medical compounds and give insights into protein engineering to strengthen O-methyltransferase activity in plants. | Yuetong Yu Yan Liu Gangqiang Dong JinZhu Jiang Liang Leng XianJu Liu Jun Zhang An Liu Sha Chen | 2023 | Horticulture Research2023，10，2： | 3 |
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