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Design and in vivo characterization of kidney-targeting multimodal micelles for renal drug delivery

Nano Research 2018年第10期11卷 5584-5595页

作者： jonathan wang Christopher Poon Deborah Chin Sarah Milkowski Vivian Lu Kenneth R. Hallows Eun Ji Chung Department of Biomedical Engineering University of Southern California Los Angeles CA 90089 USA Division of Nephrology and Hypertension Department of Medicine Keck School of Medicine University of Southern California Los Angeles CA 90033 USA USC/UKRO Kidney Research Center Keck School of Medicine University of Southern California Los Angeles CA 90033 USA Norris Comprehensive Cancer Center University of Southern California Los Angeles CA 90033 USA Department of Stem Cell Biology and Regenerative Medicine University of Southern California Los Angeles CA 90033 USA Mork Family Department of Chemical Engineering and Materials Science University of Southern California Los Angeles CA 90089 USA

One in three Americans is at risk for developing chronic kidney disease （CKD） and end-stage renal disease （ESRD）, leading to the need for dialysis or a kidney transplant. Small-molecule drugs have been proposed as therapies to manage kidney diseases, but high dosages are often required to achieve therapeutic efficacy, generating off-target side effects, some of which are lethal. To address these limitations, we developed a novel kidney-targeting multimodal micelle （KM） system for drug delivery applications. SpecificaU~ we incorporated the kidney-targeting peptide （Lysine-Lysine-Glutamic acid-Glutamic acid-Glutamic acid）3-Lysine）（（KKEEE）3K） into micelles. This peptide binds to megalin, a multi-ligand cell surface receptor present on renal tubule cells. When incubated with human kidney proximal tubule cells, KMs were found to be biocompatible in vitro. In vivo, KMs showed higher accumulation in the kidneys as compared to a non-targeted （NT） control upon intravenous injection in wild-type C57BL/6J mice. Histological evaluation showed no signs of tissue damage, while blood urea nitrogen （BUN） and creatinine levels were within normal ranges, validating the preservation of kidney health upon micelle administration. To our knowledge, this is the first utilization of （KKEEE）BK in a nanoparticle formulation, and our study offers strong evidence that this novel nanoparticle platform can be used as a candidate drug delivery carrier to direct therapeutics to diseased tissue in CKD.

关键词： micelle kidney disease renal targeting biodistribution nanoparticle

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Tree mycorrhizal associations determine how biodiversity,large trees,and environmental factors drive aboveground carbon stock in temperate forests

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Forest Ecosystems 2024年第4期11卷 448-456页

作者： Yue Chen Zikun Mao jonathan A.Myers Jinghua Yu Xugao wang CAS Key Laboratory of Forest Ecology and Silviculture Institute of Applied EcologyChinese Academy of SciencesShenyang110016China University of Chinese Academy of Sciences Beijing100049China Key Laboratory of Terrestrial Ecosystem Carbon Neutrality Shenyang110016China Department of Biology Washington University in St.LouisSt.LouisMissouriUSA

Biodiversity,large trees,and environmental conditions such as climate and soil have important effects on forest carbon ***,recent studies in temperate forests suggest that the relative importance of these factors depends on tree mycorrhizal associations,whereby large-tree effects may be driven by ectomycorrhizal(EM)trees,diversity effects may be driven by arbuscular mycorrhizal(AM)trees,and environment effects may depend on differential climate and soil preferences of AM and EM *** test this hypothesis,we used forest-inventory data consisting of over 80,000 trees from 631 temperate-forest plots(30 m×30 m)across Northeast China to examine how biodiversity(species diversity and ecological uniqueness),large trees(top 1%of tree diameters),and environmental factors(climate and soil nutrients)differently regulate aboveground carbon stocks of AM trees,EM trees,and AM and EM trees combined(*** aboveground carbon stock).We found that large trees had a positive effect on both AM and EM tree carbon ***,biodiversity and environmental factors had opposite effects on AM *** tree carbon ***,the two components of biodiversity had positive effects on AM tree carbon stocks,but negative effects on EM tree carbon *** heterogeneity(mean annual temperature and soil nutrients)also exhibited contrasting effects on AM and EM tree carbon ***,for the total carbon stock,the positive large-tree effect far surpasses the diversity and environment *** is mainly because when integrating AM and EM tree carbon stock into total carbon stock,the opposite diversity-effect(also environment-effect)on AM *** tree carbon stock counteracts each other while the consistent positive large-tree effect on AM and EM tree carbon stock is *** summary,this study emphasized a mycorrhizal viewpoint to better understand the determinants of overarching aboveground carbon profile across regional forests.

关键词： Biodiversity Ecological uniqueness Environment heterogeneity Large trees Mycorrhizal associations Tree carbon stock

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DNA G-Quadruplexes as Targets for Natural Product Drug Discovery

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Engineering 2024年第7期38卷 39-51页

作者： Kai-Bo wang Yingying wang jonathan Dickerhoff Danzhou Yang Borch Department of Medicinal Chemistry and Molecular Pharmacology College of PharmacyPurdue UniversityWest LafayetteIN 47907USA Purdue Center for Cancer Research Purdue UniversityWest LafayetteIN 47907USA Department of Chemistry Purdue UniversityWest LafayetteIN 47907USA Purdue Institute for Drug Discovery Purdue UniversityWest LafayetteIN 47907USA Jiangsu Key Laboratory of Bioactive Natural Product Research&State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China

DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA *** structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer ***,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,BCL2,KRAS,and *** products have long been an important source of drug discovery,particularly in the fields of cancer and infectious *** progress has recently been made in the discovery of naturally occurring DNA G4-targeting *** DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-b-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many ***,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focusing on understanding the structural recognition of DNA G4s by small molecules derived from *** also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.

关键词： G-quadruplex Natural products Alkaloids Cancer Promoter

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An Overview on the Composition and Age of Upper Crust of Proto-Tethyan Lajishan Intra-oceanic Arc,NE Tibet Plateau

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Acta Geologica Sinica(English Edition) 2024年第2期98卷 285-302页

作者： FU Changlei HE Xiaohu YAN Zhen jonathan CAITCHISON XIAO Wenjiao wang Bingzhang LI Wufu LI Yusen SinoProbe Laboratory Institute of GeologyChinese Academy of Geological SciencesBeijing 100037China Key Laboratory of the Northern Qinghai–Tibet Plateau Geological Processes and Mineral Resources Qinghai Geological Survey InstituteXining 810012China Department of Geology School of Earth SciencesYunnan UniversityKunming 650091China School of Earth and Environmental Sciences University of QueenslandBrisbane 4072Australia Xinjiang Institute of Ecology and Geography Chinese Academy of SciencesUrumqi 830011China State Key Laboratory of Lithospheric Evolution Institute of Geology and GeophysicsChinese Academy of SciencesBeijing 100029China School of Earth Science and Resources China University of GeosciencesBeijing 100083China

Identification and anatomy of oceanic arcs within ancient orogenic belt are significant for better understanding the tectonic framework and closure process of paleo-ocean *** article summarizes the geological,geochemical,and geochronological characteristics of upper crust of Proto-Tethyan Lajishan intra-oceanic arc and provides new data to constrain the subduction evolution of the South Qilian *** intra-oceanic arc volcanic rocks,including intermediate-mafic lava,breccia,tuff,and minor felsic rocks,are distributed along southern part of the Lajishan ophiolite *** and isotopic compositions indicate that the intermediate-mafic lava were originated from depleted mantle contaminated by sediment melts or hydrous fluids,whereas the felsic rocks were likely generated by partial melting of juvenile mafic crust in intra-oceanic arc *** from felsic rocks yield consistent and concordant ages ranging from 506 to 523 Ma,suggesting these volcanic rocks represent the relicts of upper crust of the Cambrian intra-oceanic *** with the Cambrian forearc ophiolite and accretionary complex,we suggest that the Cambrian intra-oceanic arc in the Lajishan ophiolite belt is belonging to the intra-oceanic arc system which was generated by south-directed subduction in the South Qilian Ocean at a relatively short interval between approximately 530 and 480 Ma.

关键词： volcanic rocks intra-oceanic arc U-Pb age Lajishan ophiolite belt South Qilian Ocean Proto-Tethyan realm

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Comprehensive Bile Acid Profiling of ABCB4-mutated Patients and the Prognostic Role of Taurine-conjugated􀀖􀄮􀀏􀀙􀄮􀀏􀀚􀄮􀀏􀀔􀀕􀄮􀀐􀀷􀁈􀁗􀁕􀁄􀁋􀁜􀁇􀁕􀁒􀁛􀁜􀁏􀁄􀁗􀁈􀁇􀀃􀀥􀁌􀁏􀁈􀀃􀀤􀁆􀁌􀁇􀀃􀁌􀁑􀀃􀀦􀁋􀁒􀁏􀁈􀁖􀁗􀁄􀁖􀁌􀁖

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Journal of Clinical and Translational Hepatology 2024年第2期12卷 151-161页

作者： Teng Liu Ren-Xue wang Jun Han Zhong-Die Li jonathan ASheps Li-Juan Zheng Xiao-Xiao Xu Victor Ling Jian-She wang Department of Pediatrics Shanghai Medical CollegeFudan UniversityThe Center for Pediatric Liver DiseasesChildren’s Hospital of Fudan UniversityShanghaiChina BC Cancer Agency VancouverBritish Columbia V5Z 1L3Canada University of Victoria-Genome BC Proteomics Center University of VictoriaVictoriaBritish Columbia V8Z 7X8Canada Shanghai Key Laboratory of Birth Defect ShanghaiChina

Background and Aims:We asked if comprehensive bile acid profiling could provide insights into the physiopathology of ABCB4-mutated patients and evaluated the prognostic value of taurine-conjugated tetrahydroxylated bile acid(tauro-THBA)in ***:Serum bile acid profiles were evaluated in 13 ABCB4-mutated patients with 65 healthy controls by ultra-high-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry(UPLC/MRM-MS).The concentration of tauro-THBA was compared between ABCB4-mutated patients with different *** areas under the curve(AUCs)of tauro-THBA were compared between ABCB11-mutated patients with native liver survival and those who died or underwent liver transplantation before 3 years of age by receiver operating characteristic curve(ROC),with another patient cohort for further ***:The overall hydrophobicity indices of bile acids in ABCB4-mutated patients(12.99±3.25 m)were significantly lower than those of healthy controls(14.02±1.74 m,p<0.000).That was due to markedly increased bile acid modifications including conjugation,sulfation,and *** in the tauro-THBA concentration in ABCB4-mutated patients with different prognoses were not *** analysis indicated that levels of tauro-THBA of<60 nM yielded an AUC of 0.900 with a sensitivity of 80%and specificity of 87.5%for ABCB11-mutated patients with different prognoses(p=0.0192).Of the 15 patients with good prognosis,14 were classified correctly and four of the five patients with a poor prognosis were classified correctly(14:15 vs.1:5,p=0.005)with tauro-THBA as a ***:Tauro-THBA concentration may be a biomarker for predicting the clinical outcome in low gammaglutamyl transferase intrahepatic cholestasis patients.

关键词： Bile acids MDR3 BSEP PFIC Liquid chromatography-mass spectrometry

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Encapsulated Fe(IV)Molecular Complex for Photoacoustic Imaging

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CCS Chemistry 2024年第5期6卷 1184-1197页

作者： Ye Xu Chao Li Zhong-Yu Yu Jiamin wang Zhaoyang Liu Chao Jiang Zhen-Feng Chen Xiaoyu Wu Ming-Xing Li Hong Yang Zhao-Xi wang jonathan L.Sessler Department of Chemistry Center for Supramolecular Chemistry and CatalysisInnovative Drug Research CenterShanghai UniversityShanghai 200444 College of Chemistry and Materials Science Shanghai Key Laboratory of Rare Earth Functional MaterialsShanghai Frontiers Science Center of Biomimetic CatalysisShanghai Normal UniversityShanghai 200234 Sijing Community Health Service Center of Songjiang District Shanghai 201601 Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources Guangxi Normal UniversityGuilin 541004 Department of Chemistry The University of Texas at AustinAustinTexas 78712-1224

stable neutral Fe(IV)complex(Fe-HDCL),readily accessible on the g scale,was found to possess high water solubility and good stability(<5%degradation over 4 h upon photoirradiation).Fe-HDCL is green and absorbs light effectively in the visible region(500–800 nm)with aλmax at 650 nm(ɛ=7830 M^(−1)cm^(−1)).Fe-HDCL also exhibits photothermal(PT)behavior comparable to single-wall carbon nanotubes in the solid *** aqueous solution,high PT conversion(η=72.6%)is achieved,and a strong hyperthermia-based inhibition of cell growth is observed upon subjecting Fe-HDCL to near-infrared 730 nm laser *** biological studies in vitro and in vivo confirmed that Fe-HDCL is biocompatible,clears readily,and allows the visual detection of blood *** subjecting mice to intravenous injection at low doses(e.g.,50μmol·kg^(−1)),Fe-HDCL also permits the photoacoustic(PA)imaging of kidneys and the evaluation of renal fibrosis in mouse *** addition,Fe-HDCL allows PA-based imaging of brain tissues,presumably reflecting its ability to pass through the blood-brain *** thus propose that Fe-HDCL has a role to play as PT agent and as a photodiagnostic.

关键词： stable Fe(IV)complex blood-brain barrier molecular cage photoacoustic imaging renal fibrosis

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A new class of crystalline X-ray induced photochromic materials assembled from anion-directed folding of a flexible cation

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Chinese Chemical Letters 2024年第8期35卷 554-557页

作者： Hong-Jin Liao Zhu Zhuo Qing Li Yoshihito Shiota jonathan P.Hill Katsuhiko Ariga Zi-Xiu Lu Lu-Yao Liu Zi-Ang Nan Wei wang You-Gui Huang CAS Key Laboratory of Design and Assembly of Functional Nanostructures and Fujian Provincial Key Laboratory of NanomaterialsFujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China College of Chemistry and Materials Science Fujian Normal UniversityFuzhou 350007China Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials Xiamen Institute of Rare Earth MaterialsHaixi InstitutesChinese Academy of SciencesXiamen 361021China Fujian Science&Technology Innovation Laboratory for Optoelectronic Information of China Fuzhou 350108China Institute for Materials Chemistry and Engineering Kyushu UniversityFukuoka 819-0395Japan World Premier International(WPI)Center for Materials Nanoarchitectonics(MANA) National Institute for Materials Science(NIMS)Ibaraki 305-0044Japan

Electron-deficient viologens are widely used as ligands or structure-directing agents(SDAs)to synthesize crystalline X-ray induced photochromic ***,a new rational strategy of anion-directed fold-ing a flexible cation(H_(2)imb)^(2+)((H_(2)imb)^(2+)=di-protonated 2,3-bis(imidazolin-2-yl)-2,3-dimethylbutane)has been ***-donating Cl−and(ZnCl4)2−are used to direct folding a flexible electron-deficient(H_(2)imb)^(2+)*** complexes(H_(2)imb)(NO_(3))2(1),(H_(2)imb)Cl2·H_(2)O(2),and(H_(2)imb)ZnCl4(3)have been synthesized in which(H_(2)imb)^(2+)crystallize in an anti-conformation,88.8°-gauche,and 51.8°-gauche,*** contrary to X-ray silent complex 1,X-ray induced photochromism has been achieved in both complex 2 and *** intermolecular charge-transfer mechanism has been elucidated and the anion directed folding of(H_(2)imb)^(2+)has been validated to be critical to yield colored long-lived charge-separated states.

关键词： Supramolecular Photochromic X-ray induced Anion-directed folding Electron-deficient viologens

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A unique subseafloor microbiosphere in the Mariana Trench driven by episodic sedimentation

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Marine Life Science & Technology 2024年第1期6卷 168-181页

作者： Jiwen Liu Da-Wei Li Xinxin He Ronghua Liu Haojin Cheng Chenglong Su Mengna Chen Yonghong wang Zhongsheng Zhao Hanyue Xu Zhangyu Cheng Zicheng wang Nikolai Pedentchouk David J.Lea-Smith jonathan D.Todd Xiaoshou Liu Meixun Zhao Xiao-Hua Zhang Frontiers Science Center for Deep Ocean Multispheres and Earth System and College of Marine Life SciencesOcean University of ChinaQingdao 266003China Laboratory for Marine Ecology and Environmental Science Laoshan LaboratoryQingdao 266237China Institute of Evolution and Marine Biodiversity Ocean University of ChinaQingdao 266003China Key Laboratory of Marine Chemistry Theory and Technology Ministry of EducationOcean University of ChinaQingdao 266100China Key Lab of Submarine Geosciences and Prospecting Techniques Ministry of Education/College of Marine GeosciencesOcean University of ChinaQingdao 266100China Key Laboratory of Physical Oceanography Ministry of Education/Research Vessel CentreOcean University of ChinaQingdao 266100China School of Environmental Sciences University of East AngliaNorwich NR47TJUK School of Biological Sciences University of East AngliaNorwich NR47TJUK

Hadal trenches are characterized by enhanced and infrequent high-rate episodic sedimentation events that likely introduce not only labile organic carbon and key nutrients but also new microbes that significantly alter the subseafloor ***,the role of high-rate episodic sedimentation in controlling the composition of the hadal subseafloor microbiosphere is ***,analyses of carbon isotope composition in a~750 cm long sediment core from the Challenger Deep revealed noncontinuous deposition,with anomalous ^(14)C ages likely caused by seismically driven mass transport and the funneling effect of trench *** community composition and diverse enzyme activities in the upper~27 cm differed from those at lower depths,probably due to sudden sediment deposition and differences in redox condition and organic matter *** lower depths,microbial population numbers,and composition remained relatively constant,except at some discrete depths with altered enzyme activity and microbial phyla abundance,possibly due to additional sudden sedimentation events of different *** is provided of a unique role for high-rate episodic sedimentation events in controlling the subsurface microbiosphere in Earth’s deepest ocean floor and highlight the need to perform thorough analysis over a large depth range to characterize hadal benthic *** depositional processes are likely crucial in shaping deep-water geochemical environments and thereby the deep subseafloor biosphere.

关键词： Hadal subseafloor Deep water sediment Mariana Trench Radiocarbon Microbial community Redox potential

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Corrosion Inhibitor Development for a Slightly Sour Environment with an Oxygen Intrusion Issue

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材料科学与工程（中英文版） 2011年第1期5卷 41-55页

作者： Hongbin wang jonathan J. Wylde Clariant Corporation North America 2. 2645 N. Crescent Ridge Drive The Woodlands Texas 7738 USA

This paper contains the results of a case history where oxygen contamination took place in a slightly sour system. Details are also given on the laboratory testing results and development of corrosion inhibitors for such an environment. The ingress of oxygen had been occasionally detected in the slight sour water injection system via storage tanks, the process system, pump seals and electrical cable to the aquifer wells. As a consequence, severe localized corrosion (>500 mpy) developed on the corrosion coupons when oxygen intrusion was recorded during the exposure period. As a stronger oxidant than H2CO3, oxygen greatly aggravates the corrosion attack by directly participating in the cathodic reaction, generally under full or partial diffusion control. Oxygen intrusion can also create a more acidic local environment through reaction with FeS solids generating elemental sulfur in the H2S containing system. However, to the author’s knowledge, few publications have systematically addressed the effect of O2 in the inhibition of carbon steel in the slightly sour system, particularly on the initiation and propagation of localized attack. In this paper, the effect of oxygen on the inhibition of slightly sour corrosion was studied by using bubble testing cells with continuous H2S/CO2 mixture gas sparging and O2 intrusion. The aim was to replicate the field observations in order to develop field mitigation methods. The methodology used to quantify the corrosion attack used weight loss corrosion coupons and linear polarization resistance (LPR) measurements. Significant findings include the magnitude of localized attacks with and without the presence of corrosion inhibitors caused by the presence of oxygen.

关键词：酸性环境入侵检测氧气缓蚀剂腐蚀抑制剂工艺系统阴极反应抑制作用

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用于农药喷施的液力式喷头雾化与沉积分布特性分析

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农药学学报 2024年第1期26卷 168-178页

作者：王士林陆岱鹏 jonathan VAN BEEK Ingrid ZWERTVAEGHER 王伟徐陶刘春唐玉新李雪 David NUYTTENS 江苏省农业科学院农业设施与装备研究所南京210014 农业部长江中下游设施农业工程重点实验室南京210014 佛兰德斯农业、渔业和食品研究所比利时梅勒尔贝克9820

在众多类型的喷头中,液力式雾化喷头因其雾化量大、能耗低、设备简单、经济性好而得到更广泛应用。研究液力式喷头的雾化与沉积特性对改善农药喷施效果具有重要的指导意义。为明确液力式喷头的类型和喷雾参数对其雾化和沉积特性的影响,... 详细信息

在众多类型的喷头中,液力式雾化喷头因其雾化量大、能耗低、设备简单、经济性好而得到更广泛应用。研究液力式喷头的雾化与沉积特性对改善农药喷施效果具有重要的指导意义。为明确液力式喷头的类型和喷雾参数对其雾化和沉积特性的影响,本文对6种类型的液力式喷头(标准扇形雾XR 110-015、防飘扇形雾DG 110-015、射流扇形雾AIXR 110-015、射流扇形雾AI 110-015、空心圆锥雾TXA 80-015和射流空心圆锥雾AITXA 80-015)的雾滴粒径、雾滴沉降速度以及沉积分布进行了测试。结果表明:6种供试喷头的雾滴粒径均随喷雾压力的增大而减小,不同喷雾压力下细雾滴(XR 110-015)和中等雾滴喷头(DG 110-015)的体积中值直径(D_(v0.5))差异较小,而粗雾滴(AIXR 110-015)和超粗雾滴喷头(AI 110-015和AITXA 80-015)对喷雾压力的敏感性更强,其雾滴的D_(v0.5)值随着喷雾压力的增加而急剧下降。雾滴沉降速度与分布特征主要由喷头类型决定,喷雾压力对雾滴沉降速度的影响较小,同一喷头在不同喷雾压力下的雾滴沉降速度分布趋势相似。相同喷雾压力下,细雾滴喷头的平均沉降速度(Vavg)高于其体积中值沉降速度(V_(v0.5)),但随着喷头雾滴的增大,中雾滴喷头和粗雾滴喷头的V_(v0.5)超过其Vavg,且雾滴的粒径越大两者差值越明显。雾滴的沉积结果显示,不同喷雾压力下各喷头的喷雾液流失率均在7.82%~9.75%范围内,各喷头在不同喷雾压力下的流量相似,且略低于其名义流量。喷雾压力对DG 110-015、XR 110-015和AIXR 110-015喷头的雾滴沉积分布均匀性无显著影响,但较高的喷雾压力可提高AITXA 80-015和TXA 80-015喷头的雾滴沉积分布均匀性。本研究可为田间施药时液力式喷头的选择和作业参数的优化提供理论指导和技术参考。

关键词：农药喷施液力式喷头喷雾雾滴谱雾滴沉降速度沉积

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