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1.
Ecol Evol ; 14(2): e11052, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38414570

ABSTRACT

Exploring how interactions between species evenness and dominant species identity affect litter decomposition processes is vital to understanding the relationship between biodiversity and ecosystem functioning in the context of global changes. We carried out a 127-day litter decomposition experiment under controlled conditions, with interactions of four species evenness types (high, medium, low and single species) and three dominant species identity (Leymus chinensis, Serratula centauroides, Artemisia capillaris). After collecting the remaining litter, we estimated how evenness and dominant species identity affected litter mass loss rate, carbon (C) loss rate, nitrogen (N) loss rate and remaining litter C/N directly or indirectly, and assessed relative mixture effects (RMEs) on litter mass loss. The main results are shown as follows. (1) By generalized linear models, litter mass loss rate was significantly affected by evenness after 69-day decomposition; N loss rate was affected by dominant species identity after 69-day decomposition, with treatment dominated by Serratula centauroides being at least 9.26% higher than that dominated by any of other species; and remaining litter C/N was affected by the interactions between evenness and dominant species identity after 30-, 69- and 127-day decomposition. (2) Twenty-three out of 27 RMEs were additive, and dominant species identity showed a significant effect on RMEs after 127-day decomposition. (3) By confirmatory path analyses, litter mass loss rate was affected by dominant species identity directly after 127-day decomposition, and by both species evenness and dominant species identity indirectly which was mediated by initial litter functional dispersion (FDis) after 30- and 69-day decomposition; remaining litter C/N was affected by evenness indirectly which was mediated by initial litter FDis after 127-day decomposition. These findings highlight the importance of evenness and dominant species identity on litter decomposition. The study provides insights into communities during retrogressive successions in semi-arid grasslands in the context of global changes.

2.
J Chem Ecol ; 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37917413

ABSTRACT

In plant-herbivore interactions, plant volatile organic compounds (VOCs) play an important role in anti-herbivore defense. Grasses and Epichloë endophytes often form defensive mutualistic symbioses. Most Epichloë species produce alkaloids to protect hosts from herbivores, but there is no strong evidence that endophytes can affect the insect resistance of their hosts by altering VOC emissions. In this study, a native dominant grass, sheepgrass (Leymus chinensis), and its herbivore, oriental migratory locust (Locusta migratoria), were used as experimental materials. We studied the effect of endophyte-associated VOC emissions on the insect resistance of L. chinensis. The results showed that endophyte infection enhanced insect resistance of the host, and locusts preferred the odor of endophyte-free (EF) leaves to that of endophyte-infected (EI) leaves. We determined the VOC profile of L. chinensis using gas chromatography-mass spectrometry (GC-MS), and found that endophyte infection decreased the pentadecane (an alkane) emission from uneaten plants, and increased the nonanal (an aldehyde) emission from eaten plants. The olfactory response experiment showed that locusts were attracted by high concentration of pentadecane, while repelled by high concentration of nonanal, indicating that Epichloë endophytes may increase locust resistance of L. chinensis by decreasing pentadecane while increasing nonanal emission. Our results suggest that endophytes can induce VOC-mediated defense in hosts in addition to producing alkaloids, contributing to a better understanding the endophyte-plant-herbivore interactions.

3.
Ecol Evol ; 13(9)2023 Sep.
Article in English | MEDLINE | ID: mdl-37664491

ABSTRACT

Understanding patterns of intraspecific trait variation can help us understand plant adaptability to environmental changes. To explore the underlying adaptation mechanisms of zonal plant species, we selected seven populations of Stipa krylovii, a dominant species in the Inner Mongolia Steppe of China, and evaluated the effects of phenotypic plasticity and genetic differentiation, the effects of climate variables on population trait differentiation, and traits coordinated patterns under each soil moisture treatment. We selected seeds from seven populations of S. krylovii in the Inner Mongolia Steppe, China, and carried out a soil moisture (2) × population origin (7) common garden experiment at Tianjin City, China, and measured ten plant traits of S. krylovii. General linear analyses were used to analyze how soil moisture and population origin affected each trait variation, Mantel tests were used to analyze population trait differentiation-geographic distance (or climatic difference) relationships, regression analyses were used to evaluate trait-climatic variable relationships, and plant trait networks (PTNs) were used to evaluate traits coordinated patterns. Both soil moisture and population origin showed significant effects on most of traits. Aboveground biomass, root-shoot ratio, leaf width, specific leaf area, and leaf nitrogen (N) content were significantly correlated with climate variables under the control condition. Specific leaf area and leaf N content were significantly correlated with climate variables under the drought condition. By PTNs, the hub trait(s) was plant height under the control condition and were aboveground biomass, root length, and specific leaf area under the drought condition. This study indicates that both phenotypic plasticity and genetic differentiation can significantly affect the adaptability of S. krylovii. In addition, soil moisture treatments show significant effects on trait-climate relationships and traits coordinated patterns. These findings provide new insights into the adaptive mechanisms of zonal species in the semiarid grassland region.

4.
Front Plant Sci ; 14: 1191904, 2023.
Article in English | MEDLINE | ID: mdl-37396649

ABSTRACT

Introduction: Increases in plant species diversity may increase the community diversity effect and produce community over-yielding. Epichloë endophytes, as symbiotic microorganisms, are also capable of regulating plant communities, but their effects on community diversity effects are often overlooked. Methods: In this experiment, we investigated the effects of endophytes on the diversity effects of host plant community biomass by constructing artificial communities with 1-species monocultures and 2- and 4-species mixtures of endophyte-infected (E+) and endophyte-free (E-) Achnatherum sibiricum and three common plants in its native habitat, which were potted in live and sterilized soil. Results and discussion: The results showed that endophyte infection significantly increased the belowground biomass and abundance of Cleistogenes squarrosa, marginally significantly increased the abundance of Stipa grandis and significantly increased the community diversity (evenness) of the 4-species mixtures. Endophyte infection also significantly increased the over-yielding effects on belowground biomass of the 4-species mixtures in the live soil, and the increase in diversity effects on belowground biomass was mainly due to the endophyte significantly increasing the complementary effects on belowground biomass. The effects of soil microorganisms on the diversity effects on belowground biomass of the 4-species mixtures were mainly derived from their influences on the complementary effects. The effects of endophytes and soil microorganisms on the diversity effects on belowground biomass of the 4-species communities were independent, and both contributed similarly to the complementary effects on belowground biomass. The finding that endophyte infection promotes belowground over-yielding in live soil at higher levels of species diversity suggests that endophytes may be one of the factors contributing to the positive relationship between species diversity and productivity and explains the stable co-existence of endophyte-infected Achnatherum sibiricum with a variety of plants in the Inner Mongolian grasslands.

5.
Sci Total Environ ; 892: 164534, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37268135

ABSTRACT

Exploring how plant-plant interactions between species and their neighbors vary with biotic and abiotic factors is vital to understanding community assembly mechanisms in the context of global changes. In this study, using a dominant species (Leymus chinensis (Trin.) Tzvel.) in the semiarid Inner Mongolia steppe as the target species and ten other species as neighbors, we carried out a microcosm experiment to evaluate how drought stress, neighbor richness and season affected the relative neighbor effect (Cint) (the ability to reduce growth of target species). The factor of season interactively affected the effect of drought stress or neighbor richness on Cint. In the summer, drought stress decreased Cint directly and indirectly by decreasing SLA hierarchical distance and neighbor biomass. In the subsequent spring, drought stress increased Cint, and neighbor richness increased Cint directly and indirectly by increasing neighbor community functional dispersion (FDis) and neighbor biomass. Specifically, SLA hierarchical distance was positively associated with neighbor biomass, while height hierarchical distance was negatively associated with neighbor biomass in both seasons, which increased Cint. These findings show that the relative importance of drought stress and neighbor richness on Cint shifted over seasons, which provides strong empirical evidence of how plant-plant interactions respond to changes in biotic and abiotic factors in the semiarid Inner Mongolia steppe over a short-term time. Furthermore, this study provides novel insight into community assembly mechanisms in the context of climatic aridity and biodiversity loss in semiarid regions.


Subject(s)
Biodiversity , Droughts , Biomass , Poaceae , Seasons , Ecosystem , Grassland
6.
J Fungi (Basel) ; 8(6)2022 Jun 10.
Article in English | MEDLINE | ID: mdl-35736102

ABSTRACT

Achnatherum sibiricum can be infected by two species of fungal endophytes, Epichloë gansuensis (Eg) and Epichloë sibirica (Es). In this study, the metabolites of Eg, Es, and their infected plants were studied by GC−MS analysis. The results showed that the metabolic profiles of Eg and Es were similar in general, and only six differential metabolites were detected. The direct effect of endophyte infection on the metabolites in A. sibiricum was that endophyte-infected plants could produce mannitol, which was not present in uninfected plants. Epichloë infection indirectly caused an increase in the soluble sugars in A. sibiricum related to growth and metabolites related to the defense against pathogens and herbivores, such as α-tocopherol, α-linolenic acid and aromatic amino acids. Epichloë infection could regulate galactose metabolism, starch and sucrose metabolism, tyrosine metabolism and phenylalanine metabolism of host grass. In addition, there was a significant positive correlation in the metabolite contents between the endophyte and the host.

7.
Phytopathology ; 112(11): 2310-2320, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35704677

ABSTRACT

Epichloë endophytes can improve the resistance of host grasses to pathogenic fungi, but the underlying mechanisms remain largely unknown. Here, we used phytohormone quantifications, gene expression analysis, and pathogenicity experiments to investigate the effect of Epichloë sibirica on the resistance of Achnatherum sibiricum to Curvularia lunata pathogens. Comparison of gene expression patterns between endophyte-infected and endophyte-free leaves revealed that endophyte infection was associated with significant induction of 1,758 and 765 differentially expressed genes in the host before and after pathogen inoculation, respectively. Functional analysis of the differentially expressed genes suggested that endophyte infection could activate the constitutive resistance of the host by increasing photosynthesis, enhancing the ability to scavenge reactive oxygen species, and actively regulating the expression of genes with function related to disease resistance. We found that endophyte infection was associated with induction of the expression of genes involved in the biosynthesis pathways of jasmonic acid, ethylene, and pipecolic acid and amplified the defense response of the jasmonic acid/ethylene co-regulated EIN/ERF1 transduction pathway and Pip-mediated TGA transduction pathway. Phytohormone quantifications showed that endophyte infection was associated with significant accumulation of jasmonic acid, ethylene, and pipecolic acid after pathogen inoculation. Exogenous phytohormone treatments confirmed that the disease index of plants was negatively related to both jasmonic acid and ethylene concentrations. Our results demonstrate that endophyte infection can not only improve the constitutive resistance of the host to phytopathogens before pathogen inoculation but also be associated with enhanced systemic resistance of the host to necrotrophs after C. lunata inoculation.


Subject(s)
Epichloe , Epichloe/genetics , Epichloe/metabolism , Poaceae/genetics , Poaceae/microbiology , Plant Growth Regulators/metabolism , Symbiosis/genetics , Plant Diseases/microbiology , Endophytes/physiology , Signal Transduction , Hormones/metabolism , Ethylenes/metabolism
8.
Sci Total Environ ; 826: 154134, 2022 Jun 20.
Article in English | MEDLINE | ID: mdl-35219658

ABSTRACT

Biodiversity changes in terrestrial communities continue in the context of global changes. However, the interactive effects of the changes in diversity at inter- and intraspecific levels as well as cascading effects from plant to soil microorganisms on ecosystem functioning under climate changes remains largely unexplored. Using grassland species in the semi-arid Inner Mongolia Steppe, we conducted a microcosm experiment to assess how drought treatment (non-drought and drought conditions), species diversity (2, 4, and 7 species) and genotypic diversity of the dominant species Leymus chinensis (1, 3, and 6 genotypes) affected ecosystem functions directly or indirectly via regulating plant community functional structure [community-weighted mean (CWM) and functional dispersion (FDis)] and soil microbial diversity (Shannon-Wiener index). Drought treatment, species and genotypic diversity significantly and interactively affected soil N, P cycle and soil multifunctionality as well as soil microbial diversity. Drought treatment significantly affected biomass, soil C cycle, CWM and soil microbial diversity. Species diversity significantly affected soil N cycle, CWM and FDis, and genotypic diversity significantly affected all soil functions and soil microbial diversity. CWM regulated the responses of all ecosystem functions except soil N cycle to the changes in soil moisture and species diversity, which supports the mass ratio hypothesis. The cascading effect from genotypic diversity to soil microbial diversity was significant on belowground biomass but not on any of the other ecosystem functions observed in this study. These findings highlight the importance of genotypic diversity of the dominant species L. chinensis in affecting belowground ecosystem functioning as well as soil microbial diversity, which should not be ignored for grassland protection and management. This study provides further insights into biodiversity and ecosystem functioning mechanisms in semi-arid grasslands in the context of global climate changes.


Subject(s)
Ecosystem , Grassland , Biodiversity , Biomass , China , Soil/chemistry
9.
Sci Total Environ ; 803: 149950, 2022 Jan 10.
Article in English | MEDLINE | ID: mdl-34487904

ABSTRACT

Understanding relationships between biodiversity and ecosystem functions (BEF) and the way in which ecosystem functions respond to changing climatic conditions or community composition is useful for predicting ecological consequences of global changes. However, how soil moisture condition, plant species richness interactively affect ecosystem functions in shrub-encroached grasslands is poorly understood. We conducted a soil moisture × species richness microcosm experiment using semi-arid grassland species with a N-fixing shrub Caragana microphylla Lam. as the dominant species to evaluate how soil moisture and plant species richness affected ecosystem functions directly or indirectly via regulating community functional structure, such as community-weighted mean values (CWM) and functional dispersion (FDis). Soil moisture and species richness interactively affected soil functions (soil C-, N-, P cycles and soil multifunctionality), with greater species richness buffering the adverse effects of soil drought. Soil moisture and species richness showed opposite effects on FDis but similar effects on CWM. FDis mediated the indirect effect of soil moisture and species richness on ecosystem functions, while CWM only mediated the indirect effect of soil moisture. More specifically, both soil moisture and plant species richness were negatively associated with soil P cycle, and the CWMPC1 contributed by traits related to resource-conservative strategy was positively associated with soil N cycle. Species richness showed a positive direct effect on total shoot biomass, which was mainly contributed by the complementarity effect of neighbor species richness. This study provides strong empirical support of how biomass and soil nutrient cycles respond to the changes of soil moisture and plant species richness in C. microphylla shrub-encroached grasslands, and insights on the mechanisms underlying the interactive effects of soil condition and community species composition on multiple ecosystem functions in N-fixing shrub encroached grasslands in semi-arid grassland regions.


Subject(s)
Ecosystem , Soil , Biodiversity , Biomass , Desert Climate , Grassland
10.
Ecol Evol ; 11(20): 14125-14134, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34707845

ABSTRACT

Both species (interspecific) richness and genotype (intraspecific) richness of dominant species have significant effects on ecosystem functioning directly or indirectly by regulating plant community functional structure. However, the similarities and differences of the effects between inter- and intraspecific levels are poorly understood. In this study, we selected the main species in the semi-arid Eurasian typical steppe as study objects and simultaneously carried out a species richness experiment and a genotype richness experiment of Stipa grandis which is one of the dominant species in this region. We investigated how plants at each of the two richness levels affected multiple ecosystem functions (biomass, soil C, N and P cycles) directly and indirectly by regulating community functional structure, including community-weighted mean trait values (CWM) and functional dispersion (FDis). Both species richness and genotype richness showed significant direct effects on soil P cycle, and FDis significantly mediated the responses of aboveground biomass and soil N cycle to the changes of species richness and the response of belowground biomass to the changes of genotype richness in S. grandis. CWM showed significant effects on biomass in the species richness experiment and soil nutrient cycles in the genotype richness experiment, independently of the levels of plant richness. These findings provide experimental insights of intraspecific richness effects into the relationships between biodiversity and ecosystem functioning, and highlight the importance of conserving the intraspecific diversity of dominant species in the semi-arid steppe regions.

11.
Sci Rep ; 9(1): 16289, 2019 11 08.
Article in English | MEDLINE | ID: mdl-31705024

ABSTRACT

Understanding community assembly mechanisms is helpful to predict community dynamics. To explore which community assembly mechanism(s) drive(s) the grassland restoration in semi-arid region, we investigated the relationships between plant trait and species relative abundance (SRA), and estimated community functional diversity indices for each community under different treatments (enclosure, grazing and mowing treatment) in a restoration region of Stipa grandis - Leymus chinensis communities in the northern China from 2010 to 2012. There was a high fraction of significant relationships between trait value and SRA, suggesting that niche theory structured the grassland restoration in this region. The functional richness was higher and the functional divergence was lower in the enclosure community than that in the grazing or mowing community, and significantly positive plant height - SRA relationship was found in the enclosure community. These findings demonstrated that limiting similarity based on niche theory was more important in structuring the enclosure community and that environmental filtering based on niche theory played a more important role in driving the grazing or mowing community. Only the factor of year significantly affected the functional evenness (FEve), and the lowest FEve in 2011 implied that the relatively lower precipitation could enhance the effect of limiting similarity on community assembly in the semi-arid grassland.


Subject(s)
Biodiversity , Ecosystem , Grassland , Poaceae , Phenotype , Quantitative Trait, Heritable
12.
Small ; 15(22): e1900903, 2019 05.
Article in English | MEDLINE | ID: mdl-31026116

ABSTRACT

Natural killer (NK) cells are a key component of the innate immune system as they can attack cancer cells without prior sensitization. However, due to lack of cell-specific receptors, NK cells are not innately able to perform targeted cancer immunotherapy. Aptamers are short single-stranded oligonucleotides that specifically recognize their targets with high affinity in a similar manner to antibodies. To render NK cells with target-specificity, synthetic CD30-specific aptamers are anchored on cell surfaces to produce aptamer-engineered NK cells (ApEn-NK) without genetic alteration or cell damage. Under surface-anchored aptamer guidance, ApEn-NK specifically bind to CD30-expressing lymphoma cells but do not react to off-target cells. The resulting specific cell binding of ApEn-NK triggers higher apoptosis/death rates of lymphoma cells compared to parental NK cells. Additionally, experiments with primary human NK cells demonstrate the potential of ApEn-NK to specifically target and kill lymphoma cells, thus presenting a potential new approach for targeted immunotherapy by NK cells.


Subject(s)
Aptamers, Nucleotide/metabolism , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Adaptive Immunity/genetics , Adaptive Immunity/physiology , Aptamers, Nucleotide/genetics , Cell Line, Tumor , Cell Proliferation/physiology , Cells, Cultured , Humans , Immunotherapy/methods , Ki-1 Antigen/metabolism , Lymphoma/immunology , Lymphoma/metabolism
13.
Sci Total Environ ; 666: 490-498, 2019 May 20.
Article in English | MEDLINE | ID: mdl-30802664

ABSTRACT

Studies have indicated that plant litter diversity can affect litter decomposition at both species diversity and genotypic diversity level within a species. However, the essence and relative importance of these two diversity levels on litter decomposition remain unknown. Here, two independent one-factor experiments, litter species diversity and litter genotypic diversity of the dominant species-Stipa grandis, were carried out to explore the effects of initial litter quality, litter composition and diversity on decomposition of mass, nitrogen (N), carbon (C) and phosphorus (P) simultaneously. The results showed that: (1) there were significant relationships between the initial litter N, C/N, lignin/N and the decomposition rate of N, between the initial litter P, N/P and the decomposition rate of P, and the litter composition significantly influenced litter mass, N, C and P remaining in both litter species and genotypic diversity experiments; and (2) litter species diversity significantly affected litter mass, N, C and P remaining, and non-additive relative mixture effects were mainly contributed by synergistic effects especially in 6-species mixtures; however, similar patterns were not found in litter genotypic diversity experiment. The present results emphasized that initial litter quality played the most important role in influencing litter decomposition of mass N, C and P, and suggested that litter species mixtures rather than litter genotypic mixtures of a dominant species could favor nutrient cycling in ecosystem of the semi-arid Inner Mongolia Steppe of China.


Subject(s)
Biodiversity , Grassland , Poaceae/genetics , China , Genotype , Plants , Poaceae/growth & development
14.
Sci Rep ; 8(1): 3148, 2018 02 16.
Article in English | MEDLINE | ID: mdl-29453378

ABSTRACT

Whether plants are able to adapt to environmental changes depends on their genetic characteristics and phenotypic plastic responses. We investigated the phenotypic responses of 7 populations of an important dominant species in semi-arid steppe of China - Stipa grandis, and then distinguished which adaptive mechanism(s), phenotypic plasticity or local adaptation, was/were involved in this species to adapt to environmental changes. (1) All traits were significantly influenced by the interaction of population and growth condition and by population in each condition, and inter-population variability (CVinter) was larger in the field than in the common garden for 8/9 traits, indicating that both phenotypic plasticity and genetic differentiation controlled the phenotypic differences of S. grandis. (2) From a functional standpoint, the significant relationships between the values of traits in the common garden and the environmental variables in their original habitats couldn't support local habitat adaptation of these traits. (3) Low CVintra, low quantitative differentiation among populations (Q ST ), and low plasticity shown in the western populations indicated the very low adaptive potential of S. grandis to environmental changes. (4) From the original habitats to the common garden which is far away from S. grandis distribution region, positive phenotypic responses were found in several populations, indicating that some original habitats have become unfavorable for S. grandis.


Subject(s)
Adaptation, Physiological , Ecosystem , Poaceae/physiology , China , Climate , Droughts , Poaceae/growth & development , Principal Component Analysis
15.
Ecol Evol ; 8(23): 11954-11963, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30598790

ABSTRACT

Plant-plant interactions play a key role in the function and structure of communities. The combined effect of drought stress and grazing disturbance on shaping plant-plant interactions is still poorly understood, while this combination is common in semiarid ecosystems. Four species including Stipa grandis, which is dominant in the typical steppe, and Stipa krylovii, Artemisia frigida, and Cleistogenes squarrosa, which are dominant species in the S. grandis degraded communities, were selected as study targets. We conducted a competition experiment (uniformly dense monoculture or mixture, respectively) under controlled conditions, including both drought stress and mowing disturbance, and calculated the relative interaction index (RII) of tiller number and RII of biomass for each species under each condition. (a) Under the same condition, the RII of tiller number and that of biomass for the same species usually showed reverse trends. (b) Mowing disturbance rather than drought stress played a negative role in influencing S. grandis' or S. krylovii's RII of tiller number and played a positive role in influencing A. frigida's RII of biomass. (c) Drought stress rather than mowing disturbance played a positive role in influencing C. squarrosa's RII of tiller number. (d) Neighbor species significantly influenced S. grandis' RII of tiller number, S. krylovii's RII of tiller number, A. frigida's RII of tiller number and biomass, and C. squarrosa's RII of biomass. These results could provide an explanation for why S. krylovii, A. frigida, and C. squarrosa can replace S. grandis and become the dominant species when S. grandis communities undergo a process of degradation due to overgrazing or climatic drought in natural communities. The present study provided powerful evidences for species replacement in the typical steppe of Inner Mongolia and elucidated the driving mechanisms of S. grandis communities' retrogressive succession.

16.
Small ; 14(4)2018 01.
Article in English | MEDLINE | ID: mdl-29205808

ABSTRACT

Chemotherapy is the mainstream treatment of anaplastic large cell lymphoma (ALCL). However, chemotherapy can cause severe adverse effects in patients because it is not ALCL-specific. In this study, a multifunctional aptamer-nanomedicine (Apt-NMed) achieving targeted chemotherapy and gene therapy of ALCL is developed. Apt-NMed is formulated by self-assembly of synthetic oligonucleotides containing CD30-specific aptamer and anaplastic lymphoma kinase (ALK)-specific siRNA followed by self-loading of the chemotherapeutic drug doxorubicin (DOX). Apt-NMed exhibits a well-defined nanostructure (diameter 59 mm) and stability in human serum. Under aptamer guidance, Apt-NMed specifically binds and internalizes targeted ALCL cells. Intracellular delivery of Apt-NMed triggers rapid DOX release for targeted ALCL chemotherapy and intracellular delivery of the ALK-specific siRNA induced ALK oncogene silencing, resulting in combined therapeutic effects. Animal model studies reveal that upon systemic administration, Apt-NMed specifically targets and selectively accumulates in ALCL tumor site, but does not react with off-target tumors in the same xenograft mouse. Importantly, Apt-NMed not only induces significantly higher inhibition in ALCL tumor growth, but also causes fewer or no side effects in treated mice compared to free DOX. Moreover, Apt-NMed treatment markedly improves the survival rate of treated mice, opening a new avenue for precision treatment of ALCL.


Subject(s)
Aptamers, Nucleotide/chemistry , Nanomedicine/methods , Animals , Doxorubicin/chemistry , Doxorubicin/therapeutic use , Genetic Therapy/methods , Humans , Lymphoma, Large-Cell, Anaplastic/drug therapy , Lymphoma, Large-Cell, Anaplastic/mortality , Lymphoma, Large-Cell, Anaplastic/therapy , Mice , Mice, SCID , Microscopy, Electron, Scanning , Microscopy, Fluorescence , Nanostructures/chemistry , RNA, Small Interfering/genetics , RNA, Small Interfering/physiology , Survival Rate , U937 Cells
17.
Theranostics ; 7(5): 1204-1213, 2017.
Article in English | MEDLINE | ID: mdl-28435459

ABSTRACT

The goal of precision therapy is to efficiently treat cancer without side effects. Aptamers are a class of small ligands composed of single-stranded oligonucleotides that bind to their targets with high affinity and specificity. In this study, we identified an ssDNA aptamer specifically targeting Maver-1 lymphoma cells with high binding affinity (Kd = 70±8 pmol/L). Interestingly, cellular cycle studies revealed that exposure of Maver-1 cells to synthetic aptamers triggered S-phase arrest of 40% of the cells (vs. 18% baseline). Confocal microscopy confirmed specific cell binding of aptamers and the resultant endocytosis into Maver-1 cells. Subsequent functional assays validated the fact that aptamer internalization into targeted cells is a prerequisite for Maver-1 cell growth inhibition. Importantly, aptamer-induced S-phase arrest induced enhanced chemotherapeutic results involving cytarabine, which primarily kills lymphoma cells at S-phase. Combination treatments revealed that aptamer re-exposure considerably primed Maver-1 cells for cytarabine chemotherapy, thus achieving a synergistic killing effect by reaching cell death rates as high as 61% (vs. 13% or 14% induced by aptamer or cytarabine treatment alone). These findings demonstrated that aptamers do not only act as molecular ligands but can also function as biotherapeutic agents by inducing S-phase arrest of lymphoma cells. In addition, logical combination of aptamer and cytarabine treatments ushers the way to a unique approach in precision lymphoma chemotherapy.


Subject(s)
Antimetabolites, Antineoplastic/metabolism , Aptamers, Nucleotide/metabolism , B-Lymphocytes/drug effects , Cell Cycle Checkpoints , Cytarabine/metabolism , Endocytosis , B-Lymphocytes/physiology , Cell Line, Tumor , Cell Proliferation/drug effects , Humans
18.
Sci Rep ; 7: 44525, 2017 03 27.
Article in English | MEDLINE | ID: mdl-28344355

ABSTRACT

Enclosures (fenced, grazing or clipping) within a certain period of years are the most common tools for restoration of degraded grasslands in temperate regions. Short-term enclosures can improve biodiversity and productivity by effectively relieving grazing pressure, while long-term enclosures can reduce species diversity. We therefore carried out a field experiment to investigate the specific causes of the reduced species diversity in Hulunbeier grassland of northern China. After eight years of enclosure, the significantly increased soil available nitrogen (AN) and available phosphorus (AvP) in enclosure community reduced nitrogen (N) limitation but most vegetation was still N limited. Many environmental factors led to decreased species richness, but increased soil AN and decreased light intensity at the community bottom were the most significant ones. Community density decreased independently of soil nutrition but significantly related to decreased species richness. Density of dominant canopy species increased, while dominant understory species decreased during assemblage-level thinning; therefore, the random-loss hypothesis was not supported. The dominant understory species responded to lower light availability by increasing their height, leaf area, and chlorophyll content. Moreover, our results were expected to provide some specific guidance for the restoration mode selection of degraded grasslands in northern China.


Subject(s)
Carbon/metabolism , Conservation of Natural Resources/methods , Nitrogen/metabolism , Poaceae/physiology , Soil/chemistry , Biodiversity , Biomass , China , Grassland , Herbivory , Light , Poaceae/radiation effects
19.
Ecol Evol ; 7(1): 14-25, 2017 01.
Article in English | MEDLINE | ID: mdl-28070271

ABSTRACT

Increasing attention has been paid to the relationship between biodiversity and ecosystem functioning (BEF) because of the rapid increase in species loss. However, over the past 20 years, most BEF studies only focused on the effect of species diversity on one or a few ecosystem functions, and only a few studies focused on ecosystem multifunctionality (i.e., the simultaneous provision of several ecosystem functions). Grassland ecosystems have important economic, environmental, and esthetic value; thus, this study focused on the heterogeneous microcommunities in grasslands under three management modes. The multifunctionality index (M-index) was assessed at community and microcommunity scales, and the relationship between species diversity and multifunctionality was investigated. The communities were found to be respectively composed of one, three, and six microcommunities in grazing, clipping, and enclosure management, based on a two-way indicator species analysis (TWINSPAN) and detrended correspondence analysis (DCA) for community structure. Biodiversity and soil indicators showed an apparent degradation of the grazing community, which had the worst M-index. Clipping and enclosure communities showed no significant difference in biodiversity indices, soil variables, and M-index; however, these indices were clearly different among microcommunities. Therefore, the microcommunity scale may be suitable to investigate the relationship between vegetation and multifunctionality in seminatural grassland ecosystems. Dominant species richness had more explanatory power for ecosystem multifunctionality than subdominant species richness, rare species richness, and the number of all species. Therefore, it is important to distinguish the role and rank of different species in the species richness-multifunctionality model; otherwise, the model might include redundant and unclear information. Communities with more codominant species whose distribution is also even might have better multifunctionality.

20.
Biomaterials ; 67: 42-51, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26204224

ABSTRACT

Oligonucleotide aptamers can specifically bind biomarkers on cancer cells and can be readily chemically modified with different functional molecules for personalized medicine. To target acute myeloid leukemia (AML) cells, we developed a single-strand DNA aptamer specific for the biomarker CD117, which is highly expressed on AML cells. Sequence alignment revealed that the aptamer contained a G-rich core region with a well-conserved functional G-quadruplex structure. Functional assays demonstrated that this synthetic aptamer was able to specifically precipitate CD117 proteins from cell lysates, selectively bound cultured and patient primary AML cells with high affinity (Kd < 5 nM), and was specifically internalized into CD117-expressing cells. For targeted AML treatment, aptamer-drug conjugates were fabricated by chemical synthesis of aptamer (Apt) with methotrexate (MTX), a central drug used in AML chemotherapy regimens. The formed Apt-MTX conjugates specifically inhibited AML cell growth, triggered cell apoptosis, and induced cell cycle arrest in G1 phase. Importantly, Apt-MTX had little effect on CD117-negative cells under the same treatment conditions. Moreover, exposure of patient marrow specimens to Apt-MTX resulted in selective growth inhibition of primary AML cells and had no toxicity to off-target background normal marrow cells within the same specimens. These findings indicate the potential clinical value of Apt-MTX for targeted AML therapy with minimal to no side effects in patients, and also open an avenue to chemical synthesis of new, targeted biotherapeutics.


Subject(s)
Aptamers, Nucleotide/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Methotrexate/therapeutic use , Molecular Targeted Therapy , Aptamers, Nucleotide/pharmacology , Base Sequence , Bone Marrow/drug effects , Bone Marrow/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , DNA, Single-Stranded , Humans , Leukemia, Myeloid, Acute/pathology , Methotrexate/chemistry , Methotrexate/pharmacology , Molecular Sequence Data , Proto-Oncogene Proteins c-kit/metabolism
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