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Development and tests of sliding contact line-powered track transporter

International Journal of Agricultural and Biological Engineering 2023年第4期16卷 68-75页

作者： Yihua Jiang Fang Yang Zihao Zhang Shanjun Li College of Engineering Huazhong Agricultural UniversityWuhan 430070China China Agriculture(Citrus)Research System Wuhan 430070China National R&D Center for Citrus Preservation Wuhan 430070China Citrus Mechanization Research Base Ministry of Agriculture and Rural AffairsWuhan 430070China Key Laboratory of Agricultural Equipment in Mid-lower Yangtze River Ministry of Agriculture and Rural AffairsWuhan 430070China

In order to solve the problems of complexity of control systems and the limited power supply of traditional fuelpowered and battery-driven transporters operating in mountainous orchards,a sliding contact line-powered track transporter was designed and manufactured based on theoretical calculations.Key components of the transporter were developed such as a PLC-based(programmable logic controller)control system,a sliding contact power supply,and transmission system,and a position limit device.The functions and performance of designed transporter were tested.The test results showed that the transporter exhibited a high stability of operation with an average operation velocity of 0.70 m/s,the maximum working slope of 48°,the maximum load of 400 kg,and the maximum remote control distance reaching 1482 m.When the power supply circuit of sliding contact line was 108.8 m in length,the maximum voltage drop was 2.4 V,and the maximum power loss was 174.72 W,which were close to the theoretical calculation values.With a single power supply cabinet,the transporter can operate normally for a maximum track distance of 175.69 m.All the technical indicators of the transporter met the design requirements,and the above-mentioned problems such as complexity of the control system and limited energy supply of the traditional mountain orchard transporter were well solved.This study can provide reference for the design and optimization of mountain orchard transporter.

关键词： mountain orchard transporter remote control sliding contact line voltage drop

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Crystal structure of a bacterial homolog to human lysosomal transporter,spinster

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Science Bulletin 2019年第18期64卷 1310-1317页

作者： Fu Zhoua Deqiang Yao Bing Rao Li Zhang Wang Nie Yan Zou Jie Zhao Yu Cao CAS Center for Excellence on Molecular Cell Science Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 201210China Institute of Precision Medicine The Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai 200125China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Department of Orthopaedics Shanghai Key Laboratory of Orthopaedic ImplantShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China

Lysosomes break down various biomolecules and spinster is one of the major efflux carriers removing degradation products from lysosomal lumen to keep it in healthy size and proper function.Although it is well established that a dysfunctional spinster will cause enlarged lysosomes and in turn lead to developmental defects and abnormal behavior in animals,little was known about the transportation mechanism and substrate specificity of spinster.Here,we report a crystal structure of spinster homolog from Hyphomonas neptunium,HnSPNS,in its inward-facing conformation with and without substrate bound.HnSPNS is crystallized in a monomer and a substrate-binding cavity was formed in the center of its transmembrane helices.A blob of electron density corresponding to its substrate was found in the cavity near a conserved residue,R42,which is locked in position by the interactions with conserved residues E129 and R122.Our results suggest that human spinster serves as a transporter translocating negativelycharged lipophilic small molecules and E129 might serve as a switch to control the conformational change via its protonation-deprotonation cycle.

关键词： Major facilitator superfamily transporter Spinster Membrane protein

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Insulin-like growth factor 1 modulates the phosphorylation, expression, and activity of organic anion transporter 3 through protein kinase A signaling pathway

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Acta Pharmaceutica Sinica B 2020年第1期10卷 186-194页

作者： Jinghui Zhang Zhou Yu Guofeng You Department of Pharmaceutics RutgersThe State University of New JerseyPiscatawayNJ 08854USA

Organic anion transporter 3(OAT3)plays a vital role in removing a broad variety of anionic drugs from kidney,thus avoiding their possible toxicity in the body.In the current study,we investigated the role of insulin-like growth factor 1(IGF-1)in the regulation of OAT3.We showed that IGF-1 induced a dose-and time-dependent increase in OAT3 transport activity,which correlated well with an increase in OAT3 expression.The IGF-1-induced increase in OAT3 expression was blocked by protein kinase A(PKA)inhibitor H89.Moreover,IGF-1 induced an increase in OAT3 phosphorylation,which was also blocked by H89.These data suggest that the IGF-1 modulation of OAT3 occurred through PKA signaling pathway.To further confirm the involvement of PKA,we treated OAT3-expressing cells with PKA activator Bt’2-cAMP,followed by examining OAT activity and phosphorylation.We showed that OAT3 activity and phosphorylation were much enhanced in Bt2-cAMP-treated cells as compared to that in control cells.Finally,linsitinib,an anticancer drug that blocks the IGF-1 receptor,abrogated IGF-1-stimulated OAT3 transport activity.In conclusion,our study demonstrated that IGF-1 regulates OAT3 expression and transport activity through PKA signaling pathway,possibly by phosphorylating the transporter.

关键词： Organic anion transporter Drug transport Regulation IGF-1 PKA Phosphorylation

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Organic anion transporter 1 and 3 contribute to traditional Chinese medicine-induced nephrotoxicity

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Chinese Journal of Natural Medicines 2020年第3期18卷 196-205页

作者： SHEN Qing-Qing WANG Jing-Jing ROY Debmalya SUN Li-Xin JIANG Zhen-Zhou ZHANG Lu-Yong HUANG Xin Jiangsu Key Laboratory of Drug Screening China Pharmaceutical UniversityNanjing 210009China Jiangsu Center for Pharmacodynamics Research and Evaluation China Pharmaceutical UniversityNanjing 210009China Key Laboratory of Drug Quality Control and Pharmacovigilance Ministry of EducationChina Pharmaceutical UniversityNanjing 210009China Center for Drug Screening and Pharmacodynamics Evaluation School of PharmacyGuangdong Pharmaceutical UniversityGuangzhou 510006China

With the internationally growing popularity of traditional Chinese medicine(TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nephrotoxic TCM drugs such as Aristolochic acid, Tripterygium wilfordii Hook. f, Rheum officinale Baill, and cinnabar mainly damage renal proximal tubules or cause interstitial nephritis. transporters in renal proximal tubule are believed to be critical in the disposition of xenobiotics. In this review, we provide information on the alteration of renal transporters by nephrotoxic TCMs, which may be helpful for understanding the nephrotoxic mechanism of TCMs and reducing adverse effects. Studies have proven that when administering nephrotoxic TCMs, the expression or function of renal transporters is altered, especially organic anion transporter 1 and 3. The alteration of these transporters may enhance the accumulation of toxic drugs or the dysfunction of endogenous toxins and subsequently sensitize the kidney to injury.transporters-related drug combination and clinical biomarkers supervision to avoid the risk of future toxicity are proposed.

关键词： Traditional Chinese medicine Nephrotoxicity Renal tubular epithelial cell Organic anion transporter Aristolochic acid Tripterygium wilfordii Hook.f. Rheum officinale Baill

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Regulation of mitochondrial NAD pool via NAD^+ transporter 2 is essential for matrix NADH homeostasis and ROS production in Arabidopsis

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Science China(Life Sciences) 2019年第8期62卷 991-1002页

作者： Lilan Luo Yajun He Yannan Zhao Qian Xu Jian Wu Haiyan Ma Hongyan Guo Lin Bai Jianru Zuo Jian-Min Zhou Hong Yu Jiayang Li State Key Laboratory of Plant Genomics and National Center for Plant Gene Research Institute of Genetics and Developmental BiologyTheInnovative Academy of Seed DesignChinese Academy of SciencesBeijing100101China University of Chinese Academy of Sciences Beijing100049China Department of Plant Sciences Weizmann Institute of ScienceRehovot 7610001Israel

Reactive oxygen species(ROS) play a crucial role in numerous biological processes in plants, including development, responses to environmental stimuli, and programmed cell death(PCD). Deficiency in MOSAIC DEATH 1(MOD1), a plastid-localized enoyl-ACP reductase essential for de novo fatty acid biosynthesis in Arabidopsis thaliana, leads to the increased malate export from chloroplasts to mitochondria, and the subsequent accumulation of mitochondria-generated ROS and PCD. In this study, we report the identification and characterization of a mod1 suppressor, som592. SOM592 encodes mitochondrion-localized NAD^+ transporter 2(NDT2). We show that the mitochondrial NAD pool is elevated in the mod1 mutant. The som592 mutation fully suppressed mitochondrial NADH hyper-accumulation, ROS production, and PCD in the mod1 mutant, indicating a causal relationship between mitochondrial NAD accumulation and ROS/PCD phenotypes. We also show that in wild-type plants, the mitochondrial NAD+uptake is involved in the regulation of ROS production in response to continuous photoperiod. Elevation of the alternative respiration pathway can suppress ROS accumulation and PCD in mod1, but leads to growth restriction. These findings uncover a regulatory mechanism for mitochondrial ROS production via NADH homeostasis in Arabidopsis thaliana that is likely important for growth regulation in response to altered photoperiod.

关键词： mitochondrial NAD pool NAD^+ transporter 2 mtROS

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Plant peroxisomal solute transporter proteins

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Journal of Integrative Plant Biology 2019年第7期61卷 817-835页

作者： Lennart Charton Anastasija Plett Nicole Linka Institute for Plant Biochemistry and Cluster of Excellence on Plant Sciences (CEPLAS) Heinrich Heine University

Plant peroxisomes are unique subcellular organelles which play an indispensable role in several key metabolic pathways, including fatty acid b-oxidation,photorespiration, and degradation of reactive oxygen species. The compartmentalization of metabolic pathways into peroxisomes is a strategy for organizing the metabolic network and improving pathway efficiency. An important prerequisite, however, is the exchange of metabolites between peroxisomes and other cell compartments. Since the first studies in the 1970s scientists contributed to understanding how solutes enter or leave this organelle.This review gives an overview about our current knowledge of the solute permeability of peroxisomal membranes described in plants, yeast, mammals and other eukaryotes. In general, peroxisomes contain in their bilayer membrane specific transporters for hydrophobic fatty acids(ABC transporter) and large cofactor molecules(carrier for ATP, NAD and CoA). Smaller solutes with molecular masses below 300–400 Da, like the organic acids malate, oxaloacetate, and 2-oxoglutarate, are shuttled via non-selective channels across the peroxisomal membrane.In comparison to yeast, human, mammals and other eukaryotes, the function of these known peroxisomal transporters and channels in plants are discussed in this review.

关键词： Plant peroxisomal solute transporter proteins

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Research and development of drug delivery systems based on drug transporter and nano-formulation

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Asian Journal of Pharmaceutical Sciences 2020年第2期15卷 220-236页

作者： Yi Peng Lu Chen Sheng Ye Yu Kang Junqing Liu Su Zeng Lushan Yu College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China The Children’s Hospital School of MedicineZhejiang UniversityHangzhou 310058China The First Affiliated Hospital School of MedicineZhejiang UniversityHangzhou 310058China

In recent years,the continuous occurrence of multi-drug resistance in the clinic has made people pay more attention to the transporter.Changes in the expression and activity of transporters can cause corresponding changes in drug pharmacokinetics and pharmacodynamics.The drug-drug interactions(DDI)caused by transporters can seriously affect drug effectiveness and toxicity.In the development of pharmaceutical preparations,people have increasingly concerned about the effects and regulation of transporters in drug effects.To improve the targeting and physicochemical properties of drugs,the development of targeted agents is very rapid.Among them,novel nano-formulations are the best.With the continuous innovation and development of nano-formulation,its application has become more and more extensive.Nano-formulation has exerted certain advantages in the drug development based on transporters,and is also involved in the combination of targeted transporters.This review focuses on the application of novel nano-agents targeting transporters and the introduction of drug-transporter-based nano-formulations.

关键词： Drug transporter Nano-formulation Drug delivery system Bioavailability P-gp

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The Plastid Envelope CHLOROPLAST MANGANESE transporter1 Is Essential for Manganese Homeostasis in Arabidopsis

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Molecular Plant 2018年第7期11卷 955-969页

作者： Marion Eisenhut Natalie Hoecker Sidsel Birkelund Schmidt Rubek Merina Basgaran Samantha Flachbart Peter Jahns Tabea Eser Stefan Geimer Seren Husted Andreas P.M. Weber Dario Leister Anja Schneider Biochemie der Pflanzen Cluster of Excellence on Plant Science (CEPLAS) Heinrich-Heine-University Di3sseldorf 40225 Desseldorf Germany Molekularbiologie der Pflanzen (Botanik) Department Biologie I Ludwig-Maximilians-University Mernchen 82152 Martinsried Germany Department of Plant and Environmental Sciences and Copenhagen Plant Science Centre (CPSC) Faculty of Science University of Copenhagen 1871 Frederiksberg Denmark Zellbiologie/Elektronenmikroskopie NW I/B1 Universit&t Bayreuth 95447 Bayreuth Germany These authors contributed equally to this article.

The transition metal manganese （Mn） is indispensable for photoautotrophic growth since photosystem II （PSII） employs an inorganic Mn4CaOs cluster for water splitting. Here, we show that the Arabidopsis membrane protein CHLOROPLAST MANGANESE transporter1 （CMT1） is involved in chloroplast Mn homeostasis. CMT1 is the closest homolog of the previously characterized thylakoid Mn transporter PHOTOSYNTHESIS-AFFECTED MUTANT71 （PAM71）. In contrast to PAM71, CMT1 resides at the chloro- plast envelope and is ubiquitously expressed. Nonetheless, like PAM71, the expression of CMT1 can also alleviate the Mn-sensitive phenotype of yeast mutant qomrl. The cmtl mutant is severely suppressed in growth, chloroplast ultrastructure, and PSII activity owing to a decrease in the amounts of pigments and thylakoid membrane proteins. The importance of CMT1 for chloroplast Mn homeostasis is demonstratedby the significant reduction in chloroplast Mn concentrations in cmtl-1, which exhibited reduced Mn binding in PSII complexes. Moreover, CMT1 expression is downregulated in Mn-surplus conditions. The pam71 cmtl-ldouble mutant resembles the cmtl-f single mutant rather than pare71 in most respects. Taken together, our results suggest that CMT1 mediates Mn2 uptake into the chloroplast stroma, and that CMT1 and PAM71 function sequentially in Mn delivery to PSII across the chloroplast envelope and the thylakoid membrane.

关键词： manganese transporter envelope chloroplast photosynthesis Arabidopsis

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The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic β-cells via Sirt1- and Pgc-1α-mediated regulation of Glut2

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Protein & Cell 2019年第6期10卷 436-449页

作者： Xinhui Wang Hong Gao Wenhui Wu Enjun Xie Yingying Yu Xuyan He Jin Li Wanru Zheng Xudong Wang Xizhi Cao Zhuoxian Meng Ligong Chen Junxia Min Fudi Wang School of Public Health The First Affiliated Hospital Institute of Translational Medicine Zhejiang University School of Medicine Hangzhou 310058 China School of Pharmaceutical Sciences State Key Laboratory of Membrane Biology Tsinghua-Peking Center for Life Sciences School of Life Sciences Tsinghua University Beijing 100084 China Department of Pathology and Pathophysiology Key Laboratory of Disease Proteomics of Zhejiang Province Zhejiang University School of Medicine Hangzhou 310058 China

Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly downregulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover,β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5-deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions.

关键词： zinc zinc transporter pancreatic islets β-cells insulin secretion

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Emerging transporter-targeted nanoparticulate drug delivery systems

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Acta Pharmaceutica Sinica B 2019年第1期9卷 49-58页

作者： Hongyan Su Yan Wang Shuo Liu Yue Wang Qian Liu Guangxuan Liu Qin Chen Department of Pharmacy Cancer Hospital of China Medical University Liaoning Cancer Hospital & Institute

transporter-targeted nanoparticulate drug delivery systems(nano-DDS) have emerged as promising nanoplatforms for efficient drug delivery. Recently, great progress in transporter-targeted strategies has been made, especially with the rapid developments in nanotherapeutics. In this review, we outline the recent advances in transporter-targeted nano-DDS. First, the emerging transporter-targeted nano-DDS developed to facilitate oral drug delivery are reviewed. These include improvements in the oral absorption of protein and peptide drugs, facilitating the intravenous-to-oral switch in cancer chemotherapy. Secondly, the recent advances in transporter-assisted brain-targeting nano-DDS are discussed,focusing on the specific transporter-based targeting strategies. Recent developments in transportermediated tumor-targeting drug delivery are also discussed. Finally, the possible transport mechanisms involved in transporter-mediated endocytosis are highlighted, with special attention to the latest findings of the interactions between membrane transporters and nano-DDS.

关键词： transporter Nano-DDS Oral delivery Brain-targeting Tumor-targeting

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