Besides the natural selection, the crops cultivated today have experienced two episodes of strong artificial selection, domestic and modern breeding. Domestication led to giant genetic structure differentiation betwee...Besides the natural selection, the crops cultivated today have experienced two episodes of strong artificial selection, domestic and modern breeding. Domestication led to giant genetic structure differentiation between cultivars and their wild species, while modern breeding made further genetic structure differentiation between the modern varieties and the landraces. In a population, diversity of the loci under strong selection is significantly lower than that of other loci. At the same time, diversity in the genomic regions flanking these selected loci also declines in the process of selection. This phenomenon is called hitchhiking effects or selection sweep in genetics. Genomic regions with selection sweep (haplotype block) could be detected after draft genome scanning (genome typing) with molecular markers in a number of released varieties or natural populations. Marker/trait association analysis in these regions would detect the loci (or QTLs) even the favored alleles (genes) in breeding or natural adaptation. Fine scanning of these genomic regions would help to determine the sizes of haplotype blocks and to discover the key genes, thereby providing very valuable information for isolation of the key genes and molecular design of new varieties. Establishment of high density genetic linkage maps in the major crops and availability of high throughput genotyping platform make it possible to discover agronomic important genes through marker/trait association analysis. On the basis of available publications, we give a brief introduction of the hitchhiking effect mapping approach in this paper using plant height, 1 000-grain weight, and phosphorus-deficiency tolerance as examples in wheat.展开更多
为推进纠删码在分布式存储系统中的应用,研究提高系统修复效率的算法。Hitchhiker码作为一种最新的具有最优存储空间和较低修复成本的纠删码,已在Hadoop等分布式系统中部署实现。针对目前Hitchhiker码采用均分的数据分配模式,存在网络...为推进纠删码在分布式存储系统中的应用,研究提高系统修复效率的算法。Hitchhiker码作为一种最新的具有最优存储空间和较低修复成本的纠删码,已在Hadoop等分布式系统中部署实现。针对目前Hitchhiker码采用均分的数据分配模式,存在网络带宽浪费的问题,提出一种最优分配的Hitchhiker编码(optimal allocation of Hitchhiker,OHitchhiker)。通过在编码的分配环节引入一种动态选择分配算法,使得OHitchhiker码可以针对不同(n,k)值选择具有最小修复代价的编码结构。理论分析以及实验结果验证了OHitchhiker码在保持较低存储空间的同时,进一步降低了下载带宽。展开更多
Objective Phoresy represents a non-parasitic association between animals of different taxa related to transportation. Members of several pseudoscorpion families are phoretic. In pseudoscorpions, phoresy may or may not...Objective Phoresy represents a non-parasitic association between animals of different taxa related to transportation. Members of several pseudoscorpion families are phoretic. In pseudoscorpions, phoresy may or may not be associated with their predatory behavior, enabling dispersal over larger distances than they could manage with their own short legs. This provides a wide distribution, and a potential food supply.展开更多
Chemotherapy is an important adjuvant treatment of glioma,while the efficacy is far from satisfactory,due not only to the biological barriers of blood-brain barrier(BBB)and blood-tumor barrier(BTB)but also to the intr...Chemotherapy is an important adjuvant treatment of glioma,while the efficacy is far from satisfactory,due not only to the biological barriers of blood-brain barrier(BBB)and blood-tumor barrier(BTB)but also to the intrinsic resistance of glioma cells via multiple survival mechanisms such as upregulation of P-glycoprotein(P-gp).To address these limitations,we report a bacteria-based drug delivery strategy for BBB/BTB transportation,glioma targeting,and chemo-sensitization.Bacteria selectively colonized into hypoxic tumor region and modulated tumor microenvironment,including macrophages repolarization and neutrophils infiltration.Specifically,tumor migration of neutrophils was employed as hitchhiking delivery of doxorubicin(DOX)-loaded bacterial outer membrane vesicles(OMVs/DOX).By virtue of the surface pathogen-associated molecular patterns derived from native bacteria,OMVs/DOX could be selectively recognized by neutrophils,thus facilitating glioma targeted delivery of drug with significantly enhanced tumor accumulation by 18-fold as compared to the classical passive targeting effect.Moreover,the P-gp expression on tumor cells was silenced by bacteria typeⅢsecretion effector to sensitize the efficacy of DOX,resulting in complete tumor eradication with 100%survival of all treated mice.In addition,the colonized bacteria were finally cleared by anti-bacterial activity of DOX to minimize the potential infection risk,and cardiotoxicity of DOX was also avoided,achieving excellent compatibility.This work provides an efficient trans-BBB/BTB drug delivery strategy via cell hitchhiking for enhanced glioma therapy.展开更多
Nanoscale ultrasound contrast agents,or nanobubbles,are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in cancer.These sub-micron particles are approxima...Nanoscale ultrasound contrast agents,or nanobubbles,are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in cancer.These sub-micron particles are approximately 10x smaller than clinically available microbubbles.This allows them to effectively traverse compromised physiological barriers and circulate for extended periods of time.While various aspects of nanobubble behavior have been previously examined,their behavior in human whole blood has not yet been explored.Accordingly,herein we examined,for the first time,the short and long-term effects of blood components on nanobubble acoustic response.We observed differences in the kinetics of backscatter from nanobubble suspensions in whole blood compared to bubbles in phosphate buffered saline(PBS),plasma,or red blood cell solutions(RBCs).Specifically,after introducing nanobubbles to fresh human whole blood,signal enhancement,or the magnitude of nonlinear ultrasound signal,gradually increased by 22.8±13.1%throughout our experiment,with peak intensity reached within 145 s.In contrast,nanobubbles in PBS had a stable signal with negligible change in intensity(1.7±3.2%)over 8 min.Under the same conditions,microbubbles made with the same lipid formulation showed a56.8±6.1%decrease in enhancement in whole blood.Subsequent confocal,fluorescent,and scanning electron microscopy analysis revealed attachment of the nanobubbles to the surface of RBCs,suggesting that direct interactions,or hitchhiking,of nanobubbles on RBCs in the presence of plasma may be a possible mechanism for the observed effects.This phenomenon could be key to extending nanobubble circulation time and has broad implications in drug delivery,where RBC interaction with nanoparticles could be exploited to improve delivery efficiency.展开更多
Compressed blood and intratumoral lymphatic vessels induced by proliferated tumor cells and elevated interstitial fluid pressure produce regional hypoxic and necrotic region within tumors,which severely reduced the ac...Compressed blood and intratumoral lymphatic vessels induced by proliferated tumor cells and elevated interstitial fluid pressure produce regional hypoxic and necrotic region within tumors,which severely reduced the accessibility of immunogenic cell death(ICD)related drugs and immune-related cells.Herein,the strategy of self-oriented deep tumor delivery by circulating monocyte/macrophage was proposed.Briefly,CS-AI including an indoleamine 2,3-dioxygenase(IDO)inhibitor indoximod(IND)and hydrophilic chitosan(CSO)linked with alanine-alanine-asparagine(AAN)was prepared,which could be selectively cleaved by legumain overexpressed in macrophages and promote the collapse in structure.Then,CS-AI was modified with mannose on the surface and further encapsulated the ICD inducer doxorubicin(DOX)to obtain M-CS-AI/DOX.Upon intravenous injection,MCS-AI/DOX was specially recognized and internalized by circulating monocyte in vivo.The formed drugs/monocyte tend to distribute in hypoxia/necrosis region guided by the homing signals released by tumor.Accumulated monocytes then further differentiated into macrophages,up-regulating the expression of legumain and promoting the sensitive-release of chemo-drug DOX,IND,and the mannose-modified CSO(M-CSO).The released IND would specifically regulate immunosuppressive tumor microenvironment,and synergistically inhibit tumor growth with immune activation elements,ICD-induced DOX,and the favorable adjuvant M-CSO.In summary,the self-oriented deep tumor delivery of legumain-cleavable nanovesicles through circulating monocyte makes it possible for reaching tumor regions inaccessible for nanoparticles and provides a novel insight for precise tumor enrichment and immune activation.展开更多
The ecology and evolutionary biology of insect-plant associations has real- ized extensive attention, especially during the past 60 years. The classifications (categorical designations) of continuous variation in bi...The ecology and evolutionary biology of insect-plant associations has real- ized extensive attention, especially during the past 60 years. The classifications (categorical designations) of continuous variation in biodiversity, ranging from global patterns (e.g., lat- itudinal gradients in species richness/diversity and degree of herbivore feeding specialization) to localized insect-plant associations that span the biospectrum from polyphenisms, polymorphisms, biotypes, demes, host races, to cryptic species, remain academically contentious. Semantic and biosystematic (taxonomical) disagreements sometimes detract from more important ecological and evolutionary processes that drive diversification, the dynamics of gene flow and local extinctions. This review addresses several aspects of insect specialization, host-associated divergence and ecological (including "hybrid") speciation, with special reference to the climate warming impacts on species borders of hybridiz- ing swallowtail butterflies (Papilionidae). Interspecific hybrid introgression may result in collapse of multi-species communities or increase species numbers via homoploid hybrid speciation. We may see diverging, merging, or emerging genotypes across hybrid zones, all part of the ongoing processes of evolution. Molecular analyses of genetic mosaics and genomic dynamics with "divergence hitchhiking", combined with ecological, ethological and physiological studies of"species porosity", have already begun to unveil some answers for some important ecological/evolutionary questions. (i) How rapidly can host-associated divergence lead to new species (and why doesn't it always do so, e.g., resulting in "incom- plete" speciation)? (ii) How might "speciation genes" function, and how/where would we find them? (iii) Can oscillations from specialists to generalists and back to specialists help explain global diversity in herbivorous insects? (iv) How could recombinant interspecific hybridization lead to divergence and speciation? From ancient phytochemically defined angiosperm affiliations to recent and very local geographical mosaics, the Papilionidae (swallowtail butterflies) have provided a model for enhanced understanding of ecological patterns and evolutionary processes, including host-associated genetic divergence, ge- nomic mosaics, genetic hitchhiking and sex-linked speciation genes. Apparent homoploid hybrid speciation in Papilio appears to have been catalyzed by climate warming-induced interspecific introgression of some, but not all, species diagnostic traits, reflecting strong divergent selection (discordant), especially on the Z (= X) chromosome. Reproductive isolation of these novel recombinant hybrid genotypes appears to be accomplished via a delayed post-diapause emergence or temporal isolation, and is perhaps aided by the thermal landscape. Changing thermal landscapes appear to have created (and may destroy) novel recombinant hybrid genotypes and hybrid species.展开更多
Most current crowdsourced logistics aim to minimize systems cost and maximize delivery capacity,but the efforts of crowdsourcers such as drivers are almost ignored.In the delivery process,drivers usually need to take ...Most current crowdsourced logistics aim to minimize systems cost and maximize delivery capacity,but the efforts of crowdsourcers such as drivers are almost ignored.In the delivery process,drivers usually need to take long-distance detours in hitchhiking rides based package deliveries.In this paper,we propose an approach that integrates offline trajectory data mining and online route-and-schedule optimization in the hitchhiking ride scenario to find optimal delivery routes for packages and drivers.Specifically,we propose a two-phase framework for the delivery route planning and scheduling.In the first phase,the historical trajectory data are mined offline to build the package transport network.In the second phase,we model the delivery route planning and package-taxi matching as an integer linear programming problem and solve it with the Gurobi optimizer.After that,taxis are scheduled to deliver packages with optimal delivery paths via a newly designed scheduling strategy.We evaluate our approach with the realworld datasets;the results show that our proposed approach can complete citywide package deliveries with a high success rate and low extra efforts of taxi drivers.展开更多
Cell-mediated drug delivery system(CDDS)has shown great potential for cancer therapy.However,a single cell-mediated drug delivery mechanism has not generally been successful,particularly for systemic administration.To...Cell-mediated drug delivery system(CDDS)has shown great potential for cancer therapy.However,a single cell-mediated drug delivery mechanism has not generally been successful,particularly for systemic administration.To augment the antitumor therapy efficacy,herein,we propose a strategy of cell relay-delivery for the use of artificially damaging/aging erythrocytes to hitchhike on circulating monocytes/macrophages for intratumoral accumulation of anticancer drugs.This biomimetic relay-delivery strategy was derived from the manner in which circulating monocytes/macrophages in body specifically engulf damaged/senescent erythrocytes and actively transmigrate into the tumor bulk.The strategy elegantly combines the natural functions of both cells,which therefore provides a new perspective to challenge current obstacles in drug delivery.According to the strategy,we developed biotinylated erythrocyte-poly(lactic-co-glycolic acid)(PLGA)nanoparticle hybrid DDSs(bE-NPs)using avidin-biotin coupling.In such a system,biotinylated erythrocytes can mimic the natural property of damaged/senescent erythrocytes,while PLGA NPs are capable of encapsulating anticancer drugs and promoting sustained drug release.Anticancer drugs can effectively target tumor sites by two steps.First,by using biotinylated erythrocytes as the carrier,the drug-loaded PLGA NPs could be specifically phagocytized by monocytes/macrophages.Second,by taking advantage of the tumor-tropic property of monocytes/macrophages,the drug-loaded PLGA NPs could be efficiently transported into the tumor bulk.After encapsulating vincristine(VIN)as the model drug,bE-NPs exhibited the most favorable antitumor effects in vitro and in vivo by the cell relay-delivery effect.These results demonstrate that the cell relay-delivery provides a potential method for improving tumor treatment efficacy.展开更多
文摘Besides the natural selection, the crops cultivated today have experienced two episodes of strong artificial selection, domestic and modern breeding. Domestication led to giant genetic structure differentiation between cultivars and their wild species, while modern breeding made further genetic structure differentiation between the modern varieties and the landraces. In a population, diversity of the loci under strong selection is significantly lower than that of other loci. At the same time, diversity in the genomic regions flanking these selected loci also declines in the process of selection. This phenomenon is called hitchhiking effects or selection sweep in genetics. Genomic regions with selection sweep (haplotype block) could be detected after draft genome scanning (genome typing) with molecular markers in a number of released varieties or natural populations. Marker/trait association analysis in these regions would detect the loci (or QTLs) even the favored alleles (genes) in breeding or natural adaptation. Fine scanning of these genomic regions would help to determine the sizes of haplotype blocks and to discover the key genes, thereby providing very valuable information for isolation of the key genes and molecular design of new varieties. Establishment of high density genetic linkage maps in the major crops and availability of high throughput genotyping platform make it possible to discover agronomic important genes through marker/trait association analysis. On the basis of available publications, we give a brief introduction of the hitchhiking effect mapping approach in this paper using plant height, 1 000-grain weight, and phosphorus-deficiency tolerance as examples in wheat.
文摘为推进纠删码在分布式存储系统中的应用,研究提高系统修复效率的算法。Hitchhiker码作为一种最新的具有最优存储空间和较低修复成本的纠删码,已在Hadoop等分布式系统中部署实现。针对目前Hitchhiker码采用均分的数据分配模式,存在网络带宽浪费的问题,提出一种最优分配的Hitchhiker编码(optimal allocation of Hitchhiker,OHitchhiker)。通过在编码的分配环节引入一种动态选择分配算法,使得OHitchhiker码可以针对不同(n,k)值选择具有最小修复代价的编码结构。理论分析以及实验结果验证了OHitchhiker码在保持较低存储空间的同时,进一步降低了下载带宽。
基金funded by the Natural Sciences and Engineering Research Council of Canada (2015-00681)the National Geographic Society, USA (EC0768-15)+1 种基金National Natural Science Foundation of China (No. 41772008)National Natural Science Foundation of China (No. 31872198)
文摘Objective Phoresy represents a non-parasitic association between animals of different taxa related to transportation. Members of several pseudoscorpion families are phoretic. In pseudoscorpions, phoresy may or may not be associated with their predatory behavior, enabling dispersal over larger distances than they could manage with their own short legs. This provides a wide distribution, and a potential food supply.
基金supported by the National Natural Science Foundation of China(Nos.U1903125,82071986,82073799,and 81771827)Natural Science Foundation of Hunan province in China(2021JJ20084)+2 种基金the Science and Technology Project of Hunan Province(2021RC4017 and 2021RC3020,China)the Furong Scholars Programme of Hunan Provincethe Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University(China)。
文摘Chemotherapy is an important adjuvant treatment of glioma,while the efficacy is far from satisfactory,due not only to the biological barriers of blood-brain barrier(BBB)and blood-tumor barrier(BTB)but also to the intrinsic resistance of glioma cells via multiple survival mechanisms such as upregulation of P-glycoprotein(P-gp).To address these limitations,we report a bacteria-based drug delivery strategy for BBB/BTB transportation,glioma targeting,and chemo-sensitization.Bacteria selectively colonized into hypoxic tumor region and modulated tumor microenvironment,including macrophages repolarization and neutrophils infiltration.Specifically,tumor migration of neutrophils was employed as hitchhiking delivery of doxorubicin(DOX)-loaded bacterial outer membrane vesicles(OMVs/DOX).By virtue of the surface pathogen-associated molecular patterns derived from native bacteria,OMVs/DOX could be selectively recognized by neutrophils,thus facilitating glioma targeted delivery of drug with significantly enhanced tumor accumulation by 18-fold as compared to the classical passive targeting effect.Moreover,the P-gp expression on tumor cells was silenced by bacteria typeⅢsecretion effector to sensitize the efficacy of DOX,resulting in complete tumor eradication with 100%survival of all treated mice.In addition,the colonized bacteria were finally cleared by anti-bacterial activity of DOX to minimize the potential infection risk,and cardiotoxicity of DOX was also avoided,achieving excellent compatibility.This work provides an efficient trans-BBB/BTB drug delivery strategy via cell hitchhiking for enhanced glioma therapy.
基金supported by the Hematopoietic Biorepository and Cellular Therapy Shared Resource of the Case Comprehensive Cancer Center(P30CA043703)the NIH grants T32GM007250,T32HL134622,,F30HL160111the National Institute of Biomedical Imaging and Bioengineering(R01EB025741,R01EB028144).
文摘Nanoscale ultrasound contrast agents,or nanobubbles,are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in cancer.These sub-micron particles are approximately 10x smaller than clinically available microbubbles.This allows them to effectively traverse compromised physiological barriers and circulate for extended periods of time.While various aspects of nanobubble behavior have been previously examined,their behavior in human whole blood has not yet been explored.Accordingly,herein we examined,for the first time,the short and long-term effects of blood components on nanobubble acoustic response.We observed differences in the kinetics of backscatter from nanobubble suspensions in whole blood compared to bubbles in phosphate buffered saline(PBS),plasma,or red blood cell solutions(RBCs).Specifically,after introducing nanobubbles to fresh human whole blood,signal enhancement,or the magnitude of nonlinear ultrasound signal,gradually increased by 22.8±13.1%throughout our experiment,with peak intensity reached within 145 s.In contrast,nanobubbles in PBS had a stable signal with negligible change in intensity(1.7±3.2%)over 8 min.Under the same conditions,microbubbles made with the same lipid formulation showed a56.8±6.1%decrease in enhancement in whole blood.Subsequent confocal,fluorescent,and scanning electron microscopy analysis revealed attachment of the nanobubbles to the surface of RBCs,suggesting that direct interactions,or hitchhiking,of nanobubbles on RBCs in the presence of plasma may be a possible mechanism for the observed effects.This phenomenon could be key to extending nanobubble circulation time and has broad implications in drug delivery,where RBC interaction with nanoparticles could be exploited to improve delivery efficiency.
基金supported by Zhejiang Provincial Natural Science Foundation of China(No.D19H300001).
文摘Compressed blood and intratumoral lymphatic vessels induced by proliferated tumor cells and elevated interstitial fluid pressure produce regional hypoxic and necrotic region within tumors,which severely reduced the accessibility of immunogenic cell death(ICD)related drugs and immune-related cells.Herein,the strategy of self-oriented deep tumor delivery by circulating monocyte/macrophage was proposed.Briefly,CS-AI including an indoleamine 2,3-dioxygenase(IDO)inhibitor indoximod(IND)and hydrophilic chitosan(CSO)linked with alanine-alanine-asparagine(AAN)was prepared,which could be selectively cleaved by legumain overexpressed in macrophages and promote the collapse in structure.Then,CS-AI was modified with mannose on the surface and further encapsulated the ICD inducer doxorubicin(DOX)to obtain M-CS-AI/DOX.Upon intravenous injection,MCS-AI/DOX was specially recognized and internalized by circulating monocyte in vivo.The formed drugs/monocyte tend to distribute in hypoxia/necrosis region guided by the homing signals released by tumor.Accumulated monocytes then further differentiated into macrophages,up-regulating the expression of legumain and promoting the sensitive-release of chemo-drug DOX,IND,and the mannose-modified CSO(M-CSO).The released IND would specifically regulate immunosuppressive tumor microenvironment,and synergistically inhibit tumor growth with immune activation elements,ICD-induced DOX,and the favorable adjuvant M-CSO.In summary,the self-oriented deep tumor delivery of legumain-cleavable nanovesicles through circulating monocyte makes it possible for reaching tumor regions inaccessible for nanoparticles and provides a novel insight for precise tumor enrichment and immune activation.
基金This review reflects decades of personally treasured friendships and assistance from colleagues in the insectplant interactions field of study. The Papilionidae research from our laboratory was supported by such academic synergism and also in part by the National Science Foundation (DEB-9201122 DEB-9510044+1 种基金 DEB 0716683 DEB 0918879) and the Michigan Agricultural Experiment Station (Project # 01644). I wish to thank all laboratory members and friends for their enthusiasm and assistance over the years, and most recently, Matthew Aardema, Rodrigo Mercader and Gabe Ording. Special thanks are extended to one particularly helpful reviewer.
文摘The ecology and evolutionary biology of insect-plant associations has real- ized extensive attention, especially during the past 60 years. The classifications (categorical designations) of continuous variation in biodiversity, ranging from global patterns (e.g., lat- itudinal gradients in species richness/diversity and degree of herbivore feeding specialization) to localized insect-plant associations that span the biospectrum from polyphenisms, polymorphisms, biotypes, demes, host races, to cryptic species, remain academically contentious. Semantic and biosystematic (taxonomical) disagreements sometimes detract from more important ecological and evolutionary processes that drive diversification, the dynamics of gene flow and local extinctions. This review addresses several aspects of insect specialization, host-associated divergence and ecological (including "hybrid") speciation, with special reference to the climate warming impacts on species borders of hybridiz- ing swallowtail butterflies (Papilionidae). Interspecific hybrid introgression may result in collapse of multi-species communities or increase species numbers via homoploid hybrid speciation. We may see diverging, merging, or emerging genotypes across hybrid zones, all part of the ongoing processes of evolution. Molecular analyses of genetic mosaics and genomic dynamics with "divergence hitchhiking", combined with ecological, ethological and physiological studies of"species porosity", have already begun to unveil some answers for some important ecological/evolutionary questions. (i) How rapidly can host-associated divergence lead to new species (and why doesn't it always do so, e.g., resulting in "incom- plete" speciation)? (ii) How might "speciation genes" function, and how/where would we find them? (iii) Can oscillations from specialists to generalists and back to specialists help explain global diversity in herbivorous insects? (iv) How could recombinant interspecific hybridization lead to divergence and speciation? From ancient phytochemically defined angiosperm affiliations to recent and very local geographical mosaics, the Papilionidae (swallowtail butterflies) have provided a model for enhanced understanding of ecological patterns and evolutionary processes, including host-associated genetic divergence, ge- nomic mosaics, genetic hitchhiking and sex-linked speciation genes. Apparent homoploid hybrid speciation in Papilio appears to have been catalyzed by climate warming-induced interspecific introgression of some, but not all, species diagnostic traits, reflecting strong divergent selection (discordant), especially on the Z (= X) chromosome. Reproductive isolation of these novel recombinant hybrid genotypes appears to be accomplished via a delayed post-diapause emergence or temporal isolation, and is perhaps aided by the thermal landscape. Changing thermal landscapes appear to have created (and may destroy) novel recombinant hybrid genotypes and hybrid species.
基金This work was supported in part by the National Natural Science Foundation of China(Grant No.61872050)in part by the Chongqing Basic and Frontier Research Program(cstc2018jcyjAX0551)+2 种基金Foundation of Chongqing Municipal Key Laboratory of Institutions of Higher Education([2017]3)Foundation of Chongqing Development and Reform Commission(2017[1007])Foundation of Chongqing Three Gorges University.Sijing Cheng and Chao Chen contributed equally to this work.Wei Zhang is the corresponding authors for this paper.
文摘Most current crowdsourced logistics aim to minimize systems cost and maximize delivery capacity,but the efforts of crowdsourcers such as drivers are almost ignored.In the delivery process,drivers usually need to take long-distance detours in hitchhiking rides based package deliveries.In this paper,we propose an approach that integrates offline trajectory data mining and online route-and-schedule optimization in the hitchhiking ride scenario to find optimal delivery routes for packages and drivers.Specifically,we propose a two-phase framework for the delivery route planning and scheduling.In the first phase,the historical trajectory data are mined offline to build the package transport network.In the second phase,we model the delivery route planning and package-taxi matching as an integer linear programming problem and solve it with the Gurobi optimizer.After that,taxis are scheduled to deliver packages with optimal delivery paths via a newly designed scheduling strategy.We evaluate our approach with the realworld datasets;the results show that our proposed approach can complete citywide package deliveries with a high success rate and low extra efforts of taxi drivers.
基金We are grateful for the financial support from National Natural Science Foundation of China(No.82073783)National Science and Technology Major Projects for“Major New Drugs Innovation and Development”(Grant No.2018ZX09711003-008-001).
文摘Cell-mediated drug delivery system(CDDS)has shown great potential for cancer therapy.However,a single cell-mediated drug delivery mechanism has not generally been successful,particularly for systemic administration.To augment the antitumor therapy efficacy,herein,we propose a strategy of cell relay-delivery for the use of artificially damaging/aging erythrocytes to hitchhike on circulating monocytes/macrophages for intratumoral accumulation of anticancer drugs.This biomimetic relay-delivery strategy was derived from the manner in which circulating monocytes/macrophages in body specifically engulf damaged/senescent erythrocytes and actively transmigrate into the tumor bulk.The strategy elegantly combines the natural functions of both cells,which therefore provides a new perspective to challenge current obstacles in drug delivery.According to the strategy,we developed biotinylated erythrocyte-poly(lactic-co-glycolic acid)(PLGA)nanoparticle hybrid DDSs(bE-NPs)using avidin-biotin coupling.In such a system,biotinylated erythrocytes can mimic the natural property of damaged/senescent erythrocytes,while PLGA NPs are capable of encapsulating anticancer drugs and promoting sustained drug release.Anticancer drugs can effectively target tumor sites by two steps.First,by using biotinylated erythrocytes as the carrier,the drug-loaded PLGA NPs could be specifically phagocytized by monocytes/macrophages.Second,by taking advantage of the tumor-tropic property of monocytes/macrophages,the drug-loaded PLGA NPs could be efficiently transported into the tumor bulk.After encapsulating vincristine(VIN)as the model drug,bE-NPs exhibited the most favorable antitumor effects in vitro and in vivo by the cell relay-delivery effect.These results demonstrate that the cell relay-delivery provides a potential method for improving tumor treatment efficacy.