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Identification and characterization of camptothecin tailoring enzymes in Nothapodytes tomentosa

Journal of Integrative Plant Biology 2024年第6期66卷 1158-1169页

作者： Yin Chen Jian-ping huang Yong-Jiang Wang Meng-Ling Tu Junheng Li Bingyan Xu Guoqing Peng jing Yang Sheng-Xiong huang State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry Kunming Institute of Botany Chinese Academy of Sciences University of Chinese Academy of Sciences Key Laboratory for Economic Plants and Biotechnology Kunming Institute of Botany Chinese Academy of Sciences

Camptothecin is a complex monoterpenoid indole alkaloid with remarkable antitumor activity. Given that two C-10 modified camptothecin derivatives,topotecan and irinotecan, have been approved as potent anticancer agents, there is a critical need for methods to access other aromatic ringfunctionalized congeners(e.g., C-9, C-10, etc.).However, contemporary methods for chemical oxidation are generally harsh and low-yielding when applied to the camptothecin scaffold, thereby limiting the development of modified derivatives. Reported herein, we have identified four tailoring enzymes responsible for C-9 modifications of camptothecin from Nothapodytes tomentosa, via metabolomic and transcriptomic analysis. These consist of a cytochrome P450(Nt CPT9H) which catalyzes the regioselective oxidation of camptothecin to 9-hydroxycamptothecin, as well as two methyltransferases(Nt OMT1/2, converting 9-hydroxycamptothecin to 9-methoxycamptothecin),and a uridine diphosphate-glycosyltransferase(Nt UGT5, decorating 9-hydroxycamptothecin to9-β-D-glucosyloxycamptothecin). Importantly, the critical residues that contribute to the specific catalytic activity of Nt CPT9H have been elucidated through molecular docking and mutagenesis experiments. This work provides a genetic basis for producing camptothecin derivatives through metabolic engineering. This will hasten the discovery of novel C-9 modified camptothecin derivatives,with profound implications for pharmaceutical manufacture.

关键词： camptothecin biosynthesis enzymatic assay Nothapodytes tomentosa tailoring enzyme transcriptomic analysis

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A versatile model with three-dimensional triangular lattice for unconventional transport and various topological effects

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National Science Review 2024年第1期11卷 204-214页

作者： jing-Yang You Gang Su Yuan ping Feng Department of Physics National University of Singapore Kavli Institute for Theoretical Sciences and CAS Center for Excellence in Topological Quantum Computation University of Chinese Academy of Sciences Centre for Advanced 2D Materials National University of Singapore

The finite Berry curvature in topological materials can induce many subtle phenomena, such as the anomalous Hall effect(AHE), spin Hall effect(SHE), anomalous Nernst effect(ANE), non-linear Hall effect(NLHE) and bulk photovoltaic effects. To explore these novel physics as well as their connection and coupling, a precise and effective model should be developed. Here, we propose such a versatile model—a 3D triangular lattice with alternating hopping parameters, which can yield various topological phases,including kagome bands, triply degenerate fermions, double Weyl semimetals and so on. We reveal that this special lattice can present unconventional transport due to its unique topological surface states and the aforementioned topological phenomena, such as AHE, ANE, NLHE and the topological photocurrent effect. In addition, we also provide a number of material candidates that have been synthesized experimentally with this lattice, and discuss two materials, including a non-magnetic triangular system for SHE, NLHE and the shift current, and a ferromagnetic triangular lattice for AHE and ANE. Our work provides an excellent platform, including both the model and materials, for the study of Berry-curvature-related physics.

关键词： three-dimensional triangular lattice different topological phases various topological effects Berry curvature

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Chronic administration of triclosan leads to liver fibrosis through hepcidin-ferroportin axis-mediated iron overload

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Journal of Environmental Sciences 2024年第3期137卷 144-154页

作者： jing Liu Lecong Zhang Fang Xu ping Zhang Yang Song College of Eco-Environmental Engineering Guizhou Minzu UniversityGuiyang 550025China The Institute of Karst Wetland Ecology Guizhou Minzu UniversityGuiyang 550025China State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China

Triclosan(TCS)has been manufactured as an antibacterial compound for half a century.Currently,it is widely used in various personal care products;however,its potential adverse effects raise a lot of attention.Here,we create a long-term oral administration mouse model and identify the corresponding hepatotoxicity of TCS.We discover that daily intragastric administration of 10 mg/kg TCS to mice for 12 weeks results in severe hepatic fibrosis.Further study displays that hepatic iron increased 18%,23%and 29%upon oral TCS treatment for4,8 and 12 weeks,respectively.Accompanied by hepatic iron variation,splenic and duodenal iron are increased,which indicates systemic iron disorder.Not only excessive iron accumulated in the liver,abnormal hepatic malondialdehyde,prostaglandin synthase 2 and glutathione peroxidase 4 are pointed to ferroptosis.Additional study uncovers that hepcidin expression increases 7%,10%,4%in serum and 2.4-,4.8-,and 2.3-fold on transcriptional levels upon TCS exposure for 4,8 and 12 weeks,individually.Taken together,the mice in the TCS-treated group show disordered systemic iron homeostasis via the upregulated hepatic hepcidin-ferroportin axis.Meanwhile,both hepatic iron overload(systemic level)and hepatocyte ferroptosis(cellular level)are accused of TCS-induced liver fibrosis.Ferriprox■,an iron scavenger,significantly ameliorates TCS-induced liver fibrosis.In summary,this study confirms the impact of TCS on liver fibrosis;a critical signal pathway is also displayed.The significance of the current study is to prompt us to reevaluate the“pros and cons”of TCS applications.

关键词： Triclosan Iron metabolism Hepcidin Hepatotoxicity Liver fibrosis

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Superiority of a Convolutional Neural Network Model over Dynamical Models in Predicting Central Pacific ENSO

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Advances in Atmospheric Sciences 2024年第1期41卷 141-154页

作者： Tingyu WANG ping huang Center for Monsoon System Research Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters(CIC-FEMD) Nanjing University of Information Science&TechnologyNanjing 210044China State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China University of Chinese Academy of Sciences Beijing 100049China

The application of deep learning is fast developing in climate prediction,in which El Ni?o–Southern Oscillation(ENSO),as the most dominant disaster-causing climate event,is a key target.Previous studies have shown that deep learning methods possess a certain level of superiority in predicting ENSO indices.The present study develops a deep learning model for predicting the spatial pattern of sea surface temperature anomalies(SSTAs)in the equatorial Pacific by training a convolutional neural network(CNN)model with historical simulations from CMIP6 models.Compared with dynamical models,the CNN model has higher skill in predicting the SSTAs in the equatorial western-central Pacific,but not in the eastern Pacific.The CNN model can successfully capture the small-scale precursors in the initial SSTAs for the development of central Pacific ENSO to distinguish the spatial mode up to a lead time of seven months.A fusion model combining the predictions of the CNN model and the dynamical models achieves higher skill than each of them for both central and eastern Pacific ENSO.

关键词： ENSO diversity deep learning ENSO prediction dynamical forecast system

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Carbene chemistry for unnatural biosynthesis

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Science China(Life Sciences) 2024年第1期67卷 204-207页

作者： jing huang Jay D.Keasling Department of Chemical and Biomolecular Engineering University of CaliforniaBerkeley 94720USA Joint BioEnergy Institute Lawrence Berkeley National LaboratoryEmeryville 94608USA Biological Systems and Engineering Division Lawrence Berkeley National LaboratoryBerkeley 94720USA Novo Nordisk Foundation Center for Biosustainability Technical University of DenmarkKongens Lyngby 2800Denmark Department of Bioengineering University of CaliforniaBerkeley 94720USA Synthetic Biochemistry Center Institute for Synthetic BiologyShenzhen Institutes for Advanced TechnologiesShenzhen 518055China

Previously,chemists working in synthesis were jealous of biologists since the enzymes found in nature usually exhibited great catalytic properties(e.g.,high catalytic efficiency,excellent selectivity such as substrate selectivity,regioselectivity and stereoselectivity).However,biological systems lack many counterparts of reactions widely used in chemical synthesis.

关键词： synthesis selectivity catalytic

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Therapeutic effect of Wendan Decoction combined with mosapride on gastroesophageal reflux disease after esophageal cancer surgery

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World Journal of Clinical Cases 2024年第13期12卷 2194-2200页

作者： Yu-jing Zhang Shen-ping Wu Department of Oncology Beijing Integrated Traditional Chinese and Western Medicine HospitalBeijing 100039China

BACKGROUND Gastroesophageal reflux disease(GERD)is a common complication of esophageal cancer surgery that can affect quality of life and increase the risk of esophageal stricture and anastomotic leakage.Wendan Decoction(WDD)is a traditional Chinese herbal formula used to treat various gastrointestinal disorders,such as gastritis,functional dyspepsia,and irritable bowel syndrome.Mosapride,a prokinetic agent,functions as a selective 5-hydroxytryptamine 4 agonist,enhancing gastrointestinal motility.AIM To evaluate the therapeutic effects of WDD combined with mosapride on GERD after esophageal cancer surgery.METHODS Eighty patients with GERD were randomly divided into treatment(receiving WDD combined with mosapride)and control(receiving mosapride alone)groups.The treatment was conducted from January 2021 to January 2023.The primary outcome was improved GERD symptoms as measured using the reflux disease questionnaire(RDQ).The secondary outcomes were improved esophageal motility(measured using esophageal manometry),gastric emptying(measured using gastric scintigraphy),and quality of life[measured via the Short Form-36(SF-36)Health Survey].RESULTS The treatment group showed a notably reduced RDQ score and improved esophageal motility parameters,such as lower esophageal sphincter pressure,peristaltic amplitude,and peristaltic velocity compared to the control group.The treatment group showed significantly higher gastric emptying rates and SF-36 scores(in both physical and mental domains)compared to the control group.No serious adverse effects were observed in either group.CONCLUSION WDD combined with mosapride is an effective and safe therapy for GERD after esophageal cancer surgery.It can improve GERD symptoms,esophageal motility,gastric emptying,and the quality of life of patients.Further studies with larger sample sizes and longer follow-up periods are required to confirm these findings.

关键词： Gastroesophageal reflux disease Esophageal cancer surgery Wendan Decoction Mosapride Treatment effects Gastroesophageal reflux disease symptoms

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Three-dimensional(3D)parametric measurements of individual gravels in the Gobi region using point cloud technique

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Journal of Arid Land 2024年第4期16卷 500-517页

作者： jing Xiangyu huang Weiyi KAN Jiangming College of Engineering Beijing Forestry UniversityBeijing 100083China Key Laboratory of State Forestry Administration on Forestry Equipment and Automation Beijing 100083China

Gobi spans a large area of China,surpassing the combined expanse of mobile dunes and semi-fixed dunes.Its presence significantly influences the movement of sand and dust.However,the complex origins and diverse materials constituting the Gobi result in notable differences in saltation processes across various Gobi surfaces.It is challenging to describe these processes according to a uniform morphology.Therefore,it becomes imperative to articulate surface characteristics through parameters such as the three-dimensional(3D)size and shape of gravel.Collecting morphology information for Gobi gravels is essential for studying its genesis and sand saltation.To enhance the efficiency and information yield of gravel parameter measurements,this study conducted field experiments in the Gobi region across Dunhuang City,Guazhou County,and Yumen City(administrated by Jiuquan City),Gansu Province,China in March 2023.A research framework and methodology for measuring 3D parameters of gravel using point cloud were developed,alongside improved calculation formulas for 3D parameters including gravel grain size,volume,flatness,roundness,sphericity,and equivalent grain size.Leveraging multi-view geometry technology for 3D reconstruction allowed for establishing an optimal data acquisition scheme characterized by high point cloud reconstruction efficiency and clear quality.Additionally,the proposed methodology incorporated point cloud clustering,segmentation,and filtering techniques to isolate individual gravel point clouds.Advanced point cloud algorithms,including the Oriented Bounding Box(OBB),point cloud slicing method,and point cloud triangulation,were then deployed to calculate the 3D parameters of individual gravels.These systematic processes allow precise and detailed characterization of individual gravels.For gravel grain size and volume,the correlation coefficients between point cloud and manual measurements all exceeded 0.9000,confirming the feasibility of the proposed methodology for measuring 3D parameters of individual gr

关键词： Gobi gravels three-dimensional(3D)parameters point cloud 3D reconstruction Random Sample Consensus(RANSAC)algorithm Density-Based Spatial Clustering of Applications with Noise(DBSCAN)

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Design optimization of a hexapod vibration isolation system for electro-optical payload

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Chinese Journal of Aeronautics 2024年第2期37卷 330-342页

作者： jing LI Weipeng LI Xiaoyan ZHANG Hai huang School of Astronautics Beihang UniversityBeijing 100191China

The electro-optical payloads on mobile platforms generally suffer undesirable vibrations generated by maneuvers and turbulence.These vibrations are in six degrees of freedom and cause line-of-sight jitters,resulting in image blurring and loss of tracking accuracy.In this paper,a Hexapod Vibration Isolation System(HVIS)is proposed and optimized to solve this problem.The optimization aims to centralize and minimize the natural frequencies of HVIS,for expanding the vibration isolation bandwidth and improving the vibration isolation in the higher frequency band.Considering that the design space for HVIS is limited and interfered with the frames of the mobile platform,a non-collision algorithm is proposed and applied in the optimization to obtain the feasible optimal design.The optimization result shows that the natural frequency bandwidth has been reduced by 42.9%,and the maximum natural frequency is reduced by 30.2%.The prototypes of initial and optimal designs are manufactured and tested.Both simulated and experimental results demonstrate the validity of the optimization,and the optimal design provides a maximum of 15 dB more isolation in rotation direction than the initial design.

关键词： Electro-optical payload Vibrations Isolation system Hexapod Optimization Non-collision design

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Understanding the Low Predictability of the 2015/16 El Niño Event Based on a Deep Learning Model

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Advances in Atmospheric Sciences 2024年第7期41卷 1313-1325页

作者： Tingyu WANG ping huang Xianke YANG Center for Monsoon System Research Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China National Space Science Center Chinese Academy of SciencesBeijing 100190China State Key Laboratory of Space Weather National Space Science CenterChinese Academy of SciencesBeijing 100190China College of Plant Science and Technology Huazhong Agricultural UniversityWuhan 430070China

The 2015/16 El Niño event ranks among the top three of the last 100 years in terms of intensity,but most dynamical models had a relatively low prediction skill for this event before the summer months.Therefore,the attribution of this particular event can help us to understand the cause of super El Niño–Southern Oscillation events and how to forecast them skillfully.The present study applies attribute methods based on a deep learning model to study the key factors related to the formation of this event.A deep learning model is trained using historical simulations from 21 CMIP6 models to predict the Niño-3.4 index.The integrated gradient method is then used to identify the key signals in the North Pacific that determine the evolution of the Niño-3.4 index.These crucial signals are then masked in the initial conditions to verify their roles in the prediction.In addition to confirming the key signals inducing the super El Niño event revealed in previous attribution studies,we identify the combined contribution of the tropical North Atlantic and the South Pacific oceans to the evolution and intensity of this event,emphasizing the crucial role of the interactions among them and the North Pacific.This approach is also applied to other El Niño events,revealing several new precursor signals.This study suggests that the deep learning method is useful in attributing the key factors inducing extreme tropical climate events.

关键词： ENSO attribution deep learning ENSO prediction extreme El Niño

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Optimal Cooperative Secondary Control for Islanded DC Microgrids via a Fully Actuated Approach

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IEEE/CAA Journal of Automatica Sinica 2024年第2期11卷 405-417页

作者： Yi Yu Guo-ping Liu Yi huang Peng Shi IEEE Shenzhen Key Laboratory of Control Theory and Intelligent Systems Southern University of Science and TechnologyShenzhen 518055China School of Electrical Engineering and Automation Wuhan UniversityWuhan 430072China School of Electrical and Mechanical Engineering the University of AdelaideSA 5005Australia Research and Innovation Centre Obuda University1034 BudapestHungary

DC-DC converter-based multi-bus DC microgrids(MGs) in series have received much attention, where the conflict between voltage recovery and current balancing has been a hot topic. The lack of models that accurately portray the electrical characteristics of actual MGs while is controller design-friendly has kept the issue active. To this end, this paper establishes a large-signal model containing the comprehensive dynamical behavior of the DC MGs based on the theory of high-order fully actuated systems, and proposes distributed optimal control based on this. The proposed secondary control method can achieve the two goals of voltage recovery and current sharing for multi-bus DC MGs. Additionally, the simple structure of the proposed approach is similar to one based on droop control, which allows this control technique to be easily implemented in a variety of modern microgrids with different configurations. In contrast to existing studies, the process of controller design in this paper is closely tied to the actual dynamics of the MGs. It is a prominent feature that enables engineers to customize the performance metrics of the system. In addition, the analysis of the stability of the closed-loop DC microgrid system, as well as the optimality and consensus of current sharing are given. Finally, a scaled-down solar and battery-based microgrid prototype with maximum power point tracking controller is developed in the laboratory to experimentally test the efficacy of the proposed control method.

关键词： DC microgrids distributed control high-order fully actuated system approach linear quadratic regulator microgrid modeling secondary control

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