Publications by authors named "Juanjuan Ma"

60 Publications

Sleep disturbance mediates the relationship between depressive symptoms and cognitive function in older adults with mild cognitive impairment.

Geriatr Nurs 2021 Jul 10;42(5):1019-1023. Epub 2021 Jul 10.

Shenzhen Qianhai Shekou Free Trade Zone Hospital, No.36, 7th Industrial Road, Nanshan District, Shenzhen City, Guangdong province, 518067, China. Electronic address:

This study examined whether and to what extent sleep disturbance mediates the effects of depressive symptoms on the cognition of individuals with mild cognitive impairment (MCI), who represent a high-risk group for developing dementia. Cross-sectional data were obtained from a sample of 204 Chinese community-dwelling older adults with MCI. MCI subjects were screened using the Montreal Cognitive Assessment, sleep quality was measured using the Pittsburgh Sleep Quality Index, and depressive symptoms were assessed using the Geriatric Depression Scale. Mediation analysis was conducted using the PROCESS macro with 10,000 bootstrap samples. The significant mediating effect of sleep quality on the association between depressive symptoms and cognition (Beta = -0.025; 95% CI, -0.054 to -0.007) explains 26% of the total effect of depressive symptoms on cognition and implies that the timely detection and management of sleep disturbance among the MCI population is highly important, especially for those with depressive symptoms.
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http://dx.doi.org/10.1016/j.gerinurse.2021.06.004DOI Listing
July 2021

Molecular mechanism of MdWUS2-MdTCP12 interaction in mediating cytokinin signaling to control axillary bud outgrowth.

J Exp Bot 2021 Jun;72(13):4822-4838

College of Life Science, Northwest A & F University, Yangling, Shaanxi 712100, China.

Shoot branching is an important factor that influences the architecture of apple trees and cytokinin is known to promote axillary bud outgrowth. The cultivar 'Fuji', which is grown on ~75% of the apple-producing area in China, exhibits poor natural branching. The TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) family genes BRANCHED1/2 (BRC1/2) are involved in integrating diverse factors that function locally to inhibit shoot branching; however, the molecular mechanism underlying the cytokinin-mediated promotion of branching that involves the repression of BRC1/2 remains unclear. In this study, we found that apple WUSCHEL2 (MdWUS2), which interacts with the co-repressor TOPLESS-RELATED9 (MdTPR9), is activated by cytokinin and regulates branching by inhibiting the activity of MdTCP12 (a BRC2 homolog). Overexpressing MdWUS2 in Arabidopsis or Nicotiana benthamiana resulted in enhanced branching. Overexpression of MdTCP12 inhibited axillary bud outgrowth in Arabidopsis, indicating that it contributes to the regulation of branching. In addition, we found that MdWUS2 interacted with MdTCP12 in vivo and in vitro and suppressed the ability of MdTCP12 to activate the transcription of its target gene, HOMEOBOX PROTEIN 53b (MdHB53b). Our results therefore suggest that MdWUS2 is involved in the cytokinin-mediated inhibition of MdTCP12 that controls bud outgrowth, and hence provide new insights into the regulation of shoot branching by cytokinin.
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http://dx.doi.org/10.1093/jxb/erab163DOI Listing
June 2021

Seasonal variations in water flux compositions controlled by leaf development: isotopic insights at the canopy-atmosphere interface.

Int J Biometeorol 2021 Apr 13. Epub 2021 Apr 13.

State Key Laboratory of Earth Surface Processes and Resource Ecology, Faculty of Geographical Science, Beijing Normal University, Beijing, 100875, China.

Water-stable isotopes provide a valuable tool for tracing plant-water interactions, particularly evapotranspiration (ET) partitioning and leaf water dynamics at the plant-atmosphere interface. However, process-based investigations of plant/leaf development and the associated isotopic dynamics of water fluxes involving isotope enrichment at plant-atmosphere interfaces at the ecosystem scale remain challenging. In this study, in situ isotopic measurements and tracer-aided models were used to study the dynamic interactions between vegetation growth and the isotopic dynamics of water fluxes (ET, soil evaporation, and transpiration) involving isotope enrichment in canopy leaves in a multispecies grassland ecosystem. The day-to-day variations in the isotopic compositions of ET flux were mainly controlled by plant growth, which could be explained by the significant logarithmic relationship determined between the leaf area index and transpiration fraction. Leaf development promoted a significant increase in the isotopic composition of ET and led to a slight decrease in the isotopic composition of water in canopy leaves. The transpiration (evaporation) isoflux acted to increase (decrease) the δO of water vapor, and the total isoflux impacts depended on the seasonal tradeoffs between transpiration and evaporation. The isotopic evidence in ET fluxes demonstrates the biotic controls on day-to-day variations in water/energy flux partitioning through transpiration activity. This study emphasizes that stable isotopes of hydrogen and oxygen are effective tools for quantitative evaluations of the hydrological component partitioning of ecosystems and plant-climate interactions.
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http://dx.doi.org/10.1007/s00484-021-02126-9DOI Listing
April 2021

Experiences of Families Following Organ Donation Consent: A Qualitative Systematic Review.

Transplant Proc 2021 Mar 19;53(2):501-512. Epub 2021 Jan 19.

Union Shenzhen Hospital (Nanshan Hospital), Shenzhen, China.

Objective: This systematic review synthesizes qualitative evidence on the experiences of donor families after consent to organ donation.

Methods: This robust, qualitative systematic review included an exhaustive search of electronic databases, including PubMed, Scopus, EBSCO PsycINFO, and CINAHL Complete. Manual searches of reference lists and gray literature were conducted to achieve a comprehensive identification of all relevant research. A qualitative study design served to capture the experiences of donor families after organ donation consent.

Results: A total of 6 articles that met the eligibility criteria were identified and included in this review. Three key themes emerged from the primary research: 1. family members were ambivalent about consent due to the ambiguity of brain death; 2. conversations about donation requirements proved uncomfortable; and 3. support is needed after donation.

Conclusions: Family members demonstrated ongoing ambivalence and distress that lasted for weeks after organ donation due to the ambiguity of brain death. Some family members were unhappy with having been approached for a conversation about organ donation. Donor families were not always able to deal with the difficulties they faced after their decision about organ donation. Health care professionals should provide ongoing care and updated information to family members. This review helped to identify family members' needs for both psychological and financial assistance.
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http://dx.doi.org/10.1016/j.transproceed.2020.09.016DOI Listing
March 2021

MdKNOX19, a class II knotted-like transcription factor of apple, plays roles in ABA signalling/sensitivity by targeting ABI5 during organ development.

Plant Sci 2021 Jan 9;302:110701. Epub 2020 Oct 9.

College of Horticulture, Northwest Agriculture and Forestry University, Yangling, Shaanxi, 712100, China; College of Life Sciences, Northwest Agriculture and Forestry University, Yangling, Shaanxi, 712100, China. Electronic address:

The ABI5 transcription factor, which is a core component of the ABA signaling pathway, affects various plant processes, including seed development and germination and responses to environmental cues. The knotted1-like homeobox (KNOX) transcription factor has crucial functions related to plant development, including the regulation of various hormones. In this study, an ABA-responsive KNOX gene, MdKNOX19, was identified in apple (Malus domestica). The overexpression of MdKNOX19 increased the ABA sensitivity of apple calli, resulting in a dramatic up-regulation in the transcription of the Arabidopsis ABI5-like MdABI5 gene. Additionally, MdKNOX19 overexpression in Micro-Tom adversely affected fruit size and seed yield as well as enhanced ABA sensitivity and up-regulated SlABI5 transcription during seed germination and early seedling development. An examination of MdKNOX19-overexpressing Arabidopsis plants also revealed severe defects in seed development and up-regulated expression of ABA-responsive genes. Furthermore, we further confirmed that MdKNOX19 binds directly to the MdABI5 promoter to activate expression. Our findings suggest MdKNOX19 is a positive regulator of ABI5 expression, and the conserved module MdKNOX19-MdABI5-ABA may contribute to organ development.
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http://dx.doi.org/10.1016/j.plantsci.2020.110701DOI Listing
January 2021

Construction of a high-density SNP-based genetic map and identification of fruit-related QTLs and candidate genes in peach [Prunus persica (L.) Batsch].

BMC Plant Biol 2020 Sep 23;20(1):438. Epub 2020 Sep 23.

College of horticulture, Northwest A&F University, Yangling, 712100, Shaanxi, China.

Background: High-density genetic mapping is a valuable tool for mapping loci that control specific traits for perennial fruit trees. Peach is an economically important fruit tree and a model Rosaceae species for genomic and genetic research. In peach, even though many molecular markers, genetic maps and QTL mappings have been reported, further research on the improvement of marker numbers, map densities, QTL accuracy and candidate gene identification is still warranted.

Results: A high-density single nucleotide polymorphism (SNP)-based peach linkage map was constructed using specific locus amplified fragment sequencing (SLAF-seq). This genetic map consisted of 7998 SLAF markers, spanning 1098.79 cM with an average distance of 0.17 cM between adjacent markers. A total of 40 QTLs and 885 annotated candidate genes were detected for 10 fruit-related traits, including fruit weight (FW), fruit diameter (FD), percentage of red skin colour (PSC), eating quality (EQ), fruit flavour (FV), red in flesh (RF), red around pit (RP), adherence to pit (AP), fruit development period (FDP) and fruit fibre content (FFC). Eighteen QTLs for soluble solid content (SSC) were identified along LGs 1, 4, 5, and 6 in 2015 and 2016, and 540 genes were annotated in QTL intervals. Thirty-two QTLs for fruit acidity content (FA) were detected on LG1, and 2, 4, 5, 6, and 1232 candidate genes were identified. The expression profiles of 2 candidate genes for SSC and 4 for FA were analysed in parents and their offspring.

Conclusions: We constructed a high-density genetic map in peach based on SLAF-seq, which may contribute to the identification of important agronomic trait loci. Ninety QTLs for 12 fruit-related traits were identified, most of which overlapped with previous reports, and some new QTLs were obtained. A large number of candidate genes for fruit-related traits were screened and identified. These results may improve our understanding of the genetic control of fruit quality traits and provide useful information in marker-assisted selection for fruit quality in peach breeding programmes.
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http://dx.doi.org/10.1186/s12870-020-02557-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510285PMC
September 2020

Genome-wide identification and expression profiling of the YUCCA gene family in Malus domestica.

Sci Rep 2020 07 2;10(1):10866. Epub 2020 Jul 2.

College of Horticulture, Northwest A&F University, Yangling, Shaanxi, 712100, China.

The plant hormone auxin is essential for plant growth and development. YUCCA proteins catalyse the rate-limiting step for endogenous auxin biosynthesis. In this study, we isolated 20 MdYUCCA genes from apple genome. MdYUCCA6a, MdYUCCA8a, and MdYUCCA10a were expressed in most organs and could support whole plant basal auxin synthesis. MdYUCCA4a, MdYUCCA10b, and MdYUCCA11a expression indicated roles for these genes in auxin biosynthesis in vegetative organs. MdYUCCA2b, MdYUCCA11b, and MdYUCCA11d were mainly expressed in flower organs. High temperature induced the expression of MdYUCCA4a, MdYUCCA6a, MdYUCCA8a, and MdYUCCA10a, and down-regulated the expression of MdYUCCA2b and MdYUCCA6b. Dual-luciferase assay indicated that MdPIF4 could trans-activate the MdYUCCA8a promoter. Overexpression of MdYUCCA8a increased IAA content, increased stem height, enhanced apical dominance, and led to silique malformation. These results provide a foundation for further investigation of the biological functions of apple MdYUCCAs.
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http://dx.doi.org/10.1038/s41598-020-66483-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331580PMC
July 2020

Development Of Novel Liposome-Encapsulated Combretastatin A4 Acylated Derivatives: Prodrug Approach For Improving Antitumor Efficacy.

Int J Nanomedicine 2019 7;14:8805-8818. Epub 2019 Nov 7.

Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian 350108, People's Republic of China.

Purpose: The objective of the present study was to develop a liposomal drug delivery system based on combretastatin A4 (CA4) prodrugs modified with varying alkyl chains and investigate the in vitro drug conversion from prodrug and in vivo antitumor effect.

Methods: The prodrug of CA4 was synthesized with stearyl chloride (18-carbon chain), palmitoyl chloride (16-carbon chain), myristoyl chloride (14-carbon chain), decanoyl chloride (10-carbon chain), and hexanoyl chloride (6-carbon chain) at the 3'-position of the CA4. Subsequently, it was encapsulated with liposomes through the thin-film evaporation method. Furthermore, the characteristics of prodrug-liposome were evaluated using in vitro drug release, conversion, and cytotoxicity assays, as well as in vivo pharmacokinetic, antitumor, and biodistribution studies.

Results: The liposome system with loaded CA4 derivatives was successfully developed with nano-size and electronegative particles. The rate of in vitro drug release and conversion was reduced as the fatty acid carbon chain lengthened. On the contrary, in vivo antitumor effects were improved with the enlargement of the fatty acid carbon chain. The results of the in vivo pharmacokinetic and tissue distribution studies indicated that the reduced rate of CA4 release with a long carbon chain could prolong the circulation time and increase the drug concentration in the tumor tissue.

Conclusion: These results suggested that the release or hydrolysis of the parent drug from the prodrug was closely related with the in vitro and in vivo properties. The slow drug release of CA4 modified with longer acyl chain could prolong the circulation time and increase the concentration of the drug in the tumor tissue. These effects play a critical role in increasing the antitumor efficacy.
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http://dx.doi.org/10.2147/IJN.S210938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844228PMC
March 2020

Being bullied and depressive symptoms in Chinese high school students: The role of social support.

Psychiatry Res 2020 02 4;284:112676. Epub 2019 Nov 4.

Community Health Service Center, Huazhong University of Science and Technology, Wuhan, 430074, PR China.

The aims of this study were to: 1) examine the relationship between being bullied and depressive symptoms; 2) explore whether the three mentioned sources of social support moderated this association; and 3) examine gender differences in the moderating effects of social support on bullying-associated depressive symptoms among Chinese high school students. A total of 1252 students were selected from three high schools in Zhenping County of Henan Province in China. The results suggest that bullying victimization is significantly associated with depressive symptoms among high school students. In addition, we found that only school-type social support had a moderating effect on depressive symptoms. Those who had been bullied but who had high levels of school support had lower levels of depressive symptoms than those with less school support. However, moderating effects of this support were only found for girls, not for boys. This study empirically supports that programs aimed at boosting social support for students from teachers and classmates, could help protect high school students from depressive symptoms.
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http://dx.doi.org/10.1016/j.psychres.2019.112676DOI Listing
February 2020

Structural Elucidation of a Novel Pectin-Polysaccharide from the Petal of Saussurea laniceps and the Mechanism of its Anti-HBV Activity.

Carbohydr Polym 2019 Nov 16;223:115077. Epub 2019 Jul 16.

College of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong Province, 510640, China. Electronic address:

A novel polysaccharide designated SLP-4 with the Mw of 19681 Da was purified from the petal of Saussurea laniceps. Monosaccharide composition analysis indicated that SLP-4 was composed of mannose, rhamnose, galacturonic acid, glucose, galactose, xylose and arabinose in a molar ratio of 0.825:2.030:14.998:0.841:8.260:4.039:6.009. Structural features indicated that SLP-4 was a typical pectin polysaccharide with a backbone containing →3,6)-Galp-(1→, →4)-GalpA-(1→, →6)-Galp-(1→, →4, 6)-Galp-(1→ and →2, 4)-Rhap-(1→ with the branches of →4)-Galp-(1→, T-Galp-(1→, →3)-Galp-(1→, T-Rhap-(1→, T-Araf-(1→, →5)-Araf-(1→, T-Glcp-(1→, →4)-Xylp-(1→ and →4)-Manp-(1→. Additionally, SLP-4 could effectively inhibit the secretion of HBsAg and HBeAg in HepG2.2.15 cells, but had little effect on the replication of HBV DNA. This inhibition didn't involve cellular pathways, and was due to the interaction between SLP-4 and HBsAg or HBeAg, which may block the ELISA detection of HBsAg and HBeAg. The present study may provide useful information for further study of SLP-4 and understanding of anti-HBV activity of polysaccharides.
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http://dx.doi.org/10.1016/j.carbpol.2019.115077DOI Listing
November 2019

Transcriptome Analysis Reveals New Insights into -Mediated Plant Growth in .

J Agric Food Chem 2019 Sep 21;67(35):9757-9771. Epub 2019 Aug 21.

effects on plant stress responses have been well documented, but little is known regarding its effects on plant growth. In this study, we functionally characterized . Overexpressing in and apple trees promoted growth. Longitudinal stem cells were longer in transgenic plants than in wild-type plants. The size and number of cells and the area of the transverse stem were greater in the transgenic lines than in the wild-type plants. Moreover, transgenic and apple plants were more sensitive to an exogenous brassinosteroid. A transcriptome analysis of wild-type and transgenic apple revealed that overexpression activated the brassinosteroid and ethylene signals, xylem production, and stress responses. Trend and Venn analyses indicated that carbohydrate, energy, and hormone metabolic activities were greater in transgenic plants during different periods. Moreover, a weighted gene coexpression network analysis proved that carbohydrate, hormone, and xylem metabolism as well as cell growth may be critical for -mediated apple tree growth and development. Compared with the corresponding levels in wild-type plants, the endogenous brassinosteroid, cytokinin, starch, sucrose, trehalose, glucose, fructose, and total sugar contents were considerably different in transgenic plants. Our results imply that helps to regulate the growth of apple tree through the above-mentioned pathways. These findings provide new information regarding the effects of onplant growth and development.
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http://dx.doi.org/10.1021/acs.jafc.9b02467DOI Listing
September 2019

Knocking out lca5 in zebrafish causes cone-rod dystrophy due to impaired outer segment protein trafficking.

Biochim Biophys Acta Mol Basis Dis 2019 10 23;1865(10):2694-2705. Epub 2019 Jul 23.

Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China. Electronic address:

Leber congenital amaurosis (LCA) is the most serious form of inherited retinal dystrophy that leads to blindness or severe visual impairment within a few months after birth. Approximately 1-2% of the reported cases are caused by mutations in the LCA5 gene. This gene encodes a ciliary protein called LCA5 that is localized to the connecting cilium of photoreceptors. The retinal phenotypes caused by LCA5 mutations and the underlying pathological mechanisms are still not well understood. In this study, we knocked out the lca5 gene in zebrafish using CRISPR/Cas9 technology. An early onset visual defect is detected by the ERG in 7 dpf lca5 zebrafish. Histological analysis by HE staining and immunofluorescence reveal progressive degeneration of rod and cone photoreceptors, with a pattern that cones are more severely affected than rods. In addition, ultrastructural analysis by transmission electron microscopy shows disordered and broken membrane discs in rods' and cones' outer segments, respectively. In our lca5 zebrafish, the red-cone opsin and cone α-transducin are selectively mislocalized to the inner segment and synaptic terminal. Moreover, we found that Ift88, a key component of the intraflagellar transport complex, is retained in the outer segments. These data suggest that the intraflagellar transport complex-mediated outer segment protein trafficking might be impaired due to lca5 deletion, which finally leads to a type of retinal degeneration mimicking the phenotype of cone-rod dystrophy in human. Our work provides a novel animal model to study the physiological function of LCA5 and develop potential treatments of LCA.
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http://dx.doi.org/10.1016/j.bbadis.2019.07.009DOI Listing
October 2019

Sequencing of a Wild Apple (Malus baccata) Genome Unravels the Differences Between Cultivated and Wild Apple Species Regarding Disease Resistance and Cold Tolerance.

G3 (Bethesda) 2019 Jul;9(7):2051-2060

College of Life Sciences, Northwest A&F University, Yangling 712100, Shannxi, China.

Malus baccata is one of four wild apple species that can hybridize with the cultivated apple species (Malus domestica). It is widely used in high-latitude apple-producing areas as a rootstock and breeding resource because of its disease resistance, and cold tolerance. A lack of a reference genome has limited the application of M. baccata for apple breeding. We present a draft reference genome for M. baccata. The assembled sequence consisting of 665 Mb, with a scaffold N50 value of 452 kb, included transposable elements (413 Mb) and 46,114 high-quality protein-coding genes. According to a genetic map derived from 390 sibling lines, 72% of the assembly and 85% of the putative genes were anchored to 17 linkage groups. Many of the M. baccata genes under positive selection pressure were associated with plant-pathogen interaction pathways. We identified 2,345 Transcription factor-encoding genes in 58 families in the M. baccata genome. Genes related to disease defense and cold tolerance were also identified. A total of 462 putative nucleotide-binding site (NBS)-leucine-rich-repeat (LRR) genes, 177 Receptor-like kinase (RLK) and 51 receptor-like proteins (RLP) genes were identified in this genome assembly. The M. baccata genome contained 3978 cold-regulated genes, and 50% of these gene promoter containing DREB motif which can be induced by CBF gene. We herein present the first M. baccata genome assembly, which may be useful for exploring genetic variations in diverse apple germplasm, and for facilitating marker-assisted breeding of new apple cultivars exhibiting resistance to disease and cold stress.
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http://dx.doi.org/10.1534/g3.119.400245DOI Listing
July 2019

Role of Cytokinin, Strigolactone, and Auxin Export on Outgrowth of Axillary Buds in Apple.

Front Plant Sci 2019 15;10:616. Epub 2019 May 15.

College of Life Science, Northwest A&F University, Yangling, China.

Shoot branching is regulated by phytohormones, including cytokinin (CK), strigolactone (SL), and auxin in axillary buds. The correlative importance of these phytohormones in the outgrowth of apple axillary buds remains unclear. In this study, the outgrowth dynamics of axillary buds of a more-branching mutant (MB) and its wild-type (WT) of were assessed using exogenous chemical treatments, transcriptome analysis, paraffin section, and reverse transcription-quantitative PCR analysis (RT-qPCR). High contents of CK and abscisic acid coincided in MB axillary buds. Exogenous CK promoted axillary bud outgrowth in the WT but not in MB, whereas exogenous gibberellic had no significant effect on bud outgrowth in the WT. Functional analysis of transcriptome data and RT-qPCR analysis of gene transcripts revealed that MB branching were associated with CK signaling, auxin transport, and SL signaling. Transcription of the SL-related genes , and in the axillary buds of MB was generally upregulated during bud outgrowth, whereas / were generally downregulated both in WT and MB. Exogenous SL inhibited outgrowth of axillary buds in the WT and the apple varieties T337, M26, and Nagafu 2, whereas axillary buds of the MB were insensitive to SL treatment. Treatment with -1-naphthylphalamic acid (NPA; an auxin transport inhibitor) inhibited bud outgrowth in plants of the WT and MB. The transcript abundance of was generally decreased in response to NPA and SL treatments, and increased in CK and decapitation treatments, whereas no consistent pattern was observed for and . Collectively, the present results suggest that in apple auxin transport from the axillary bud to the stem may be essential for the outgrowth of axillary buds, and at least, is involved in the process of bud outgrowth.
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http://dx.doi.org/10.3389/fpls.2019.00616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530649PMC
May 2019

Sequencing of a Wild Apple () Genome Unravels the Differences Between Cultivated and Wild Apple Species Regarding Disease Resistance and Cold Tolerance.

G3 (Bethesda) 2019 07 9;9(7):2051-2060. Epub 2019 Jul 9.

College of Life Sciences, Northwest A&F University, Yangling 712100, Shannxi, China

is one of four wild apple species that can hybridize with the cultivated apple species (). It is widely used in high-latitude apple-producing areas as a rootstock and breeding resource because of its disease resistance, and cold tolerance. A lack of a reference genome has limited the application of for apple breeding. We present a draft reference genome for The assembled sequence consisting of 665 Mb, with a scaffold N50 value of 452 kb, included transposable elements (413 Mb) and 46,114 high-quality protein-coding genes. According to a genetic map derived from 390 sibling lines, 72% of the assembly and 85% of the putative genes were anchored to 17 linkage groups. Many of the genes under positive selection pressure were associated with plant-pathogen interaction pathways. We identified 2,345 Transcription factor-encoding genes in 58 families in the genome. Genes related to disease defense and cold tolerance were also identified. A total of 462 putative nucleotide-binding site (NBS)-leucine-rich-repeat (LRR) genes, 177 Receptor-like kinase (RLK) and 51 receptor-like proteins (RLP) genes were identified in this genome assembly. The genome contained 3978 cold-regulated genes, and 50% of these gene promoter containing DREB motif which can be induced by gene. We herein present the first genome assembly, which may be useful for exploring genetic variations in diverse apple germplasm, and for facilitating marker-assisted breeding of new apple cultivars exhibiting resistance to disease and cold stress.
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http://dx.doi.org/10.1534/g3.119.400245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643876PMC
July 2019

Novel SN38 derivative-based liposome as anticancer prodrug: an in vitro and in vivo study.

Int J Nanomedicine 2019 20;14:75-85. Epub 2018 Dec 20.

Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433, People's Republic of China,

Background: Many novel drug delivery systems have been extensively studied to exploit the full therapeutic potential of SN38, which is one of the most potent antitumor analogs of camptothecins (CPTs), whose clinical application is seriously hindered by poor water solubility, low plasmatic stability, and severe toxicity, but results are always unsatisfactory.

Methods: In this study, combining the advantages of prodrug and nanotechnology, a lipophilic prodrug of SN38, SN38-PA, was developed by conjugating palmitic acid to SN38 via ester bond at C position, and then the lipophilic prodrug was encapsulated into a long-circulating liposomal carrier by film dispersion method.

Results: The SN38-PA liposomes were characterized as follows: an average particle size of 80.13 nm, an average zeta potential of -33.53 mv, and the entrapment efficiency of 99%. Compared with CPT-11, SN38-PA liposome was more stable in close lactone form, more efficient in conversion rate to SN38, and more potent in cytotoxicity against tumor cells. Pharmacokinetic study showed that SN38-PA liposome had significantly enhanced plasma half-life (t) value of SN38 and increased area under the curve (AUC) of SN38, which was 7.5-fold higher than that of CPT-11. Biodistribution study showed that SN38-PA liposome had more active metabolite SN38 in each tissue. Finally, the pharmacodynamic study showed that SN38-PA liposome had higher antitumor effect with the antitumor inhibition rate of 1.61 times than that of CPT-11.

Conclusion: These encouraging data merit further investigation on this novel SN38-PA liposome.
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http://dx.doi.org/10.2147/IJN.S187906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304248PMC
February 2019

Genome-wide identification of SERK genes in apple and analyses of their role in stress responses and growth.

BMC Genomics 2018 Dec 27;19(1):962. Epub 2018 Dec 27.

College of Horticulture, Northwest Agriculture & Forestry University, Yangling, 712100, Shaanxi, China.

Background: Somatic embryogenesis receptor-like kinases (SERKs) are leucine-rich repeat receptor-like kinases associated with various signaling pathways. These kinases have a relationship with stress signals, and they are also believed to be important for regulating plant growth. However, information about this protein family in apple is limited.

Results: Twelve apple SERK genes distributed across eight chromosomes were identified. These genes clustered into three distinct groups in a phylogenetic analysis. All of the encoded proteins contained typical SERK domains. The chromosomal locations, gene/protein structures, synteny, promoter sequences, protein-protein interactions, and physicochemical characteristics of MdSERK genes were analyzed. Bioinformatics analyses demonstrated that gene duplications have likely contributed to the expansion and evolution of SERK genes in the apple genome. Six homologs of SERK genes were identified between apple and Arabidopsis. Quantitative real-time PCR analyses revealed that the MdSERK genes showed different expression patterns in various tissues. Eight MdSERK genes were responsive to stress signals, such as methyl jasmonate, salicylic acid, abscisic acid, and salt (NaCl). The application of exogenous brassinosteroid and auxin increased the growth and endogenous hormone contents of Malus hupehensis seedlings. The expression levels of seven MdSERK genes were significantly upregulated by brassinosteroid and auxin. In addition, several MdSERK genes showed higher expression levels in standard trees of 'Nagafu 2' (CF)/CF than in dwarf trees of CF/'Malling 9' (M.9), and in CF than in the spur-type bud mutation "Yanfu 6" (YF).

Conclusion: This study represents the first comprehensive investigation of the apple SERK gene family. These data indicate that apple SERKs may function in adaptation to adverse environmental conditions and may also play roles in controlling apple tree growth.
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http://dx.doi.org/10.1186/s12864-018-5342-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307271PMC
December 2018

Expression of genes in the potential regulatory pathways controlling alternate bearing in 'Fuji' (Malus domestica Borkh.) apple trees during flower induction.

Plant Physiol Biochem 2018 Nov 9;132:579-589. Epub 2018 Oct 9.

College of Horticulture, Northwest A & F University, Yangling, Shaanxi, 712100, China. Electronic address:

Most perennial fruit trees have an alternate bearing problem where a heavy fruit load is produced one year (ON year) but few flowers and fruits produced the next year (OFF year), resulting in a significant fluctuation in production. In the present study, comparative transcriptome analysis of terminal buds of apple (Malus domestica Borkh., cv. Nagafu No. 2) trees was conducted during the floral induction period in the ON and OFF years to identify the potential regulatory pathways controlling alternate bearing. A total of 1027 differentially expressed genes (DEGs), most of which were involved in secondary metabolism, sugar metabolism, plant hormone pathways, were identified. The analysis focused on differences in sugar content and hormone levels between the ON and OFF trees. Sucrose content, zeatin-riboside (ZR), and abscisic acid (ABA) levels were lower in ON-year buds than in OFF-year buds. ON buds also had elevated levels of gibberellins (GAs), with a higher expression of GA20 oxidase (GA20ox) and a significant lower level of RGA-like2 (RGL2). Expression analyses also revealed a significantly higher level of SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE genes (MdSPL1, MdSPL6 and MdSPL12) transcripts levels in buds of OFF trees at 45 days after full bloom (DAFB). LEAFY (LFY) expression increased significantly prior to flower induction in OFF buds. These findings provide new information of the role of hormones in alternate bearing, as well as other processes, and provide new insights into the molecular mechanisms regulating alternate bearing in perennial fruit trees.
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http://dx.doi.org/10.1016/j.plaphy.2018.10.003DOI Listing
November 2018

Molecular role of cytokinin in bud activation and outgrowth in apple branching based on transcriptomic analysis.

Plant Mol Biol 2018 Oct 11;98(3):261-274. Epub 2018 Oct 11.

Department of Horticulture College, Northwest Agriculture & Forestry University, Yangling, 712100, Shaanxi, China.

Key Message: Axillary bud activation and outgrowth were dependent on local cytokinin, and that bud activation preceded the activation of cell cycle and cell growth genes in apple branching. Cytokinin is often applied to apple trees to produce more shoot branches in apple seedlings. The molecular response of apple to the application of cytokinin, and the relationship between bud activation and cell cycle in apple branching, however, are poorly understood. In this study, RNA sequencing was used to characterize differential expression genes in axillary buds of 1-year grafted "Fuji" apple at 4 and 96 h after cytokinin application. And comparative gene expression analyses were performed in buds of decapitated shoots and buds of the treatment of biosynthetic inhibitor of cytokinin (Lovastatin) on decapitated shoots. Results indicated that decapitation and cytokinin increased ZR content in buds and internodes at 4-8 h, and induced bud elongation at 96 h after treatment, relative to buds in shoots receiving the Lovastatin treatment. RNA-seq analysis indicated that differential expression genes in auxin and cytokinin signal transduction were significantly enriched at 4 h, and DNA replication was enriched at 96 h. Cytokinin-responsive type-A response regulator, auxin polar transport, and axillary meristem-related genes were up-regulated at 4 h in the cytokinin and decapitation treatments, while qRT-PCR analysis showed that cell cycle and cell growth genes were up-regulated after 8 h. Collectively, the data indicated that bud activation and outgrowth might be dependent on local cytokinin synthesis in axillary buds or stems, and that bud activation preceded the activation of cell cycle genes during the outgrowth of ABs in apple shoots.
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http://dx.doi.org/10.1007/s11103-018-0781-2DOI Listing
October 2018

Genome-wide identification and expression analysis of brassinosteroid biosynthesis and metabolism genes regulating apple tree shoot and lateral root growth.

J Plant Physiol 2018 Dec 10;231:68-85. Epub 2018 Sep 10.

College of Horticulture, Northwest A&F University, Yangling, Shaanxi 712100, China; College of Life Science, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address:

In plants, brassinosteroid biosynthesis and metabolism genes affect endogenous brassinosteroid metabolic processes as well as stem and root growth. However, there is little information available regarding these genes in apple. In this study, 22 brassinosteroid biosynthesis and metabolism genes were identified in apple (Malus domestica). These genes were named according to their chromosomal locations and the Arabidopsis thaliana homologs. Their conserved characteristic domains, evolutionary relationships, syntenic relationships, chemical characteristics, gene/protein structures, interactions among the encoded proteins, promoter sequences, and functions were investigated. These 22 genes were clustered with their A. thaliana homologs based on bioinformatics analyses, which suggested they are functionally similar in apple and A. thaliana. Tissue-specific expression levels revealed that most of these genes are important for stem growth and development, while several of these genes affect lateral root formation. The transcription patterns of these genes in shoot tips were investigated following diverse treatments [brassinosteroid (shoot tips and roots), brassinazole, auxin, and temperature]. Gene expression levels were also examined in different grafting combinations ('Nagafu No. 2'/Malling 9 and 'Nagafu No. 2'/'Nagafu No. 2') and shoot varieties ('Yanfu No. 6' and 'Nagafu No. 2'). The results indicated that these genes may be involved in apple stem and root growth. The comprehensive genome-wide analysis of brassinosteroid biosynthesis and metabolism genes presented herein may be useful for breeding new apple cultivars with increased vigor. The data also represent a rich genetic resource for future apple gene functional investigations that may have implications for the genetic improvement of apple tree species.
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http://dx.doi.org/10.1016/j.jplph.2018.09.002DOI Listing
December 2018

Two novel polysaccharides from the torus of Saussurea laniceps protect against AAPH-induced oxidative damage in human erythrocytes.

Carbohydr Polym 2018 Nov 7;200:446-455. Epub 2018 Aug 7.

College of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong Province 510640, China. Electronic address:

Two major polysaccharides (SLT-3, SLT-4) were isolated from the torus of Saussurea laniceps. Their molecular weight, monosaccharide compositions and the ability to protect human erythrocytes from oxidative damage induced by AAPH were assessed. Results showed that the Mw of SLT-3 and SLT-4 were 10,113 Da and 12,392 Da. SLT-3 was composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, xylose, and arabinose in a molar ratio of 0.25:0.53:0.19:15.35:0.51:1.10:0.63:1.73, whereas SLT-4 was composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose in a molar ratio of 0.92:5.61:0.93:19.50:2.42:5.27:3.01. Pretreatment with SLT-3 and SLT-4 reduced MDA content, inhibited the generation of intracellular ROS and maintained the balance of GSH and GSSG in AAPH-treated erythrocytes. Furthermore, the activities of intracellular antioxidant enzymes, such as SOD, GSH-Px and CAT, were attenuated in polysaccharide treated cells. The results provide an important basis for the development of S. laniceps as a natural antioxidant.
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http://dx.doi.org/10.1016/j.carbpol.2018.08.007DOI Listing
November 2018

Exogenous application of GA inactively regulates axillary bud outgrowth by influencing of branching-inhibitors and bud-regulating hormones in apple (Malus domestica Borkh.).

Mol Genet Genomics 2018 Dec 16;293(6):1547-1563. Epub 2018 Aug 16.

College of Horticulture, Northwest A & F University, Yangling, 712100, Shaanxi, China.

Although gibberellin (GA) has been reported to control branching, little is known about how GA mediates signals regulating the outgrowth of axillary buds (ABs). In the current study, the effect of the exogenous application of 5.0 mM GA on ABs outgrowth on 1-year-old 'Nagafu No. 2'/T337/M. robusta Rehd. apple trees was investigated and compared to the bud-activating treatments, 5 mM BA or decapitation. Additionally, the expression of genes related to bud-regulating signals and sucrose levels in ABs was examined. Results indicated that GA did not promote ABs' outgrowth, nor down-regulate the expression of branching repressors [MdTCP40, MdTCP33, and MdTCP16 (homologs of BRANCHED1 and BRC2)], which were significantly inhibited by the BA and decapitation treatments. MdSBP12 and MdSBP18, the putative transcriptional activators of these genes, which are expressed at lower levels in BA-treated and decapitated buds, were up-regulated in the GA treatment in comparison to the BA treatment. Additionally, GA did not up-regulate the expression of CK response- and auxin transport-related genes, which were immediately induced by the BA treatment. In addition, GA also up-regulated the expression of several Tre6P biosynthesis genes and reduced sucrose levels in ABs. Sucrose levels, however, were still higher than what was observed in BA-treated buds, indicating that sucrose may not be limiting in GA-controlled AB outgrowth. Although GA promoted cell division, it was not sufficient to induce AB outgrowth. Conclusively, some branching-inhibiting genes and bud-regulating hormones are associated with the inability of GA to activate AB outgrowth.
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http://dx.doi.org/10.1007/s00438-018-1481-yDOI Listing
December 2018

MicroRNA‑155 promotes ox‑LDL‑induced autophagy in human umbilical vein endothelial cells by targeting the PI3K/Akt/mTOR pathway.

Mol Med Rep 2018 Sep 29;18(3):2798-2806. Epub 2018 Jun 29.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.

Endothelial cell autophagy has a protective role in inhibiting inflammation and preventing the development of atherosclerosis, which may be regulated by microRNA (miR)‑155. The present study aimed to investigate the mechanisms of autophagy in the development of atherosclerosis. Human umbilical vein endothelial cells model in vitro and using oxidized low‑density lipoprotein (ox‑LDL) stimulated cells to simulate the atherosclerosis. MiR‑155 mimics, miR‑155 inhibitors, and a negative control were respectively transfected in human umbilical vein endothelial cells to analyzed alterations in the expression of miR‑155. It was demonstrated that overexpression of miR‑155 promoted autophagic activity in oxidized low‑density lipoprotein‑stimulated human umbilical vein endothelial cells, whereas inhibition of the expression of miR‑155 reduced autophagic activity. Overexpression of miR‑155 revealed that it regulated autophagy via the phosphatidylinositol‑3 kinase (PI3K)/RAC‑α serine/threonine‑protein kinase (Akt)/mechanistic target of rapamycin pathway (mTOR) signaling pathway. A luciferase reporter assay demonstrated that miR‑155 directly bound to the PI3K catalytic subunit a and Ras homolog enriched in brain 3'‑untranslated region and inhibited its luciferase activity. Therefore, the results of the present study suggested that miR‑155 promoted autophagy in vascular endothelial cells and that this may have occurred via targeting of the PI3K/Akt/mTOR pathway. Thus, miR‑155 may be considered as a potential therapeutic target for the treatment of atherosclerosis.
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http://dx.doi.org/10.3892/mmr.2018.9236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102700PMC
September 2018

Kinetics and thermodynamics of urea hydrolysis under the coupling of nitrogen application rate and temperature.

Environ Sci Pollut Res Int 2018 Sep 27;25(25):25413-25419. Epub 2018 Jun 27.

College of Water Science and Engineering, Taiyuan University of Technology, Taiyuan, 030024, China.

This study aimed to determine the coupled effects of temperature and urea application rate on kinetic and thermodynamic parameters to supplement the mechanism of urea hydrolysis and modify the Arrhenius model to improve the prediction accuracy of urea content. Laboratory experiments were conducted for sandy loam soil under different temperatures (T) (288, 293, 298, and 308 K) and urea application rates (F) (247, 309, 371, and 433 mg kg). Urea content was determined daily through high-performance liquid chromatography. Results showed that the interaction between temperature and urea application rate had a significant effect on reaction rate (K) and half-life (H), whereas no significant effect on activation degree (lgN), activation free energy (ΔG), activation enthalpy (ΔH), and activation entropy (ΔS). The new K(T)-2 model with a determination coefficient (R) = 0.990 was more accurate than the Arrhenius model with R = 0.965. The new U(T, F) model with a mean absolute percentage error (MAPE) = 3.62% was more accurate than the traditional U(T) model with a MAPE = 6.38%. The effects of T and F were observed mainly during the preparatory stage and the most critical transition stage of the chemical reaction, respectively. The findings ΔH > 0, ΔG > 0, and ΔS < 0 indicated that urea hydrolysis was endothermic and controlled by enthalpy. These results supplemented the mechanism of urea hydrolysis and improved the prediction accuracy of urea content.
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http://dx.doi.org/10.1007/s11356-018-2576-zDOI Listing
September 2018

Prediction of soil urea conversion and quantification of the importance degrees of influencing factors through a new combinatorial model based on cluster method and artificial neural network.

Chemosphere 2018 May 6;199:676-683. Epub 2018 Feb 6.

College of Water Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, China. Electronic address:

Quantitative prediction of soil urea conversion is crucial in determining the mechanism of nitrogen transformation and understanding the dynamics of soil nutrients. This study aimed to establish a combinatorial prediction model (MCA-F-ANN) for soil urea conversion and quantify the relative importance degrees (RIDs) of influencing factors with the MCA-F-ANN method. Data samples were obtained from laboratory culture experiments, and soil nitrogen content and physicochemical properties were measured every other day. Results showed that when MCA-F-ANN was used, the mean-absolute-percent error values of NH-N, NO-N, and NH contents were 3.180%, 2.756%, and 3.656%, respectively. MCA-F-ANN predicted urea transformation under multi-factor coupling conditions more accurately than traditional models did. The RIDs of reaction time (RT), electrical conductivity (EC), temperature (T), pH, nitrogen application rate (F), and moisture content (W) were 32.2%-36.5%, 24.0%-28.9%, 12.8%-15.2%, 9.8%-12.5%, 7.8%-11.0%, and 3.5%-6.0%, respectively. The RIDs of the influencing factors in a descending order showed the pattern RT > EC > T > pH > F > W. RT and EC were the key factors in the urea conversion process. The prediction accuracy of urea transformation process was improved, and the RIDs of the influencing factors were quantified.
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http://dx.doi.org/10.1016/j.chemosphere.2018.01.151DOI Listing
May 2018

Identification and expression analysis of the IPT and CKX gene families during axillary bud outgrowth in apple (Malus domestica Borkh.).

Gene 2018 Apr 1;651:106-117. Epub 2018 Feb 1.

College of Horticulture, Northwest A & F University, Yangling, Shaanxi 712100, China. Electronic address:

Cytokinins (CKs) play a crucial role in promoting axillary bud outgrowth and targeting the control of CK metabolism can be used to enhance branching in plants. CK levels are maintained mainly by CK biosynthesis (isopentenyl transferase, IPT) and degradation (dehydrogenase, CKX) genes in plants. A systematic study of the IPT and CKX gene families in apple, however, has not been conducted. In the present study, 12 MdIPTs and 12 MdCKXs were identified in the apple genome. Systematic phylogenetic, structural, and synteny analyses were performed. Expression analysis of these genes in different tissues was also assessed. MdIPT and MdCKX genes exhibit distinct expression patterns in different tissues. The response of MdIPT, MdCKX, and MdPIN1 genes to various treatments (6-BA, decapitation and Lovastatin, an inhibitor of CKs synthesis) that impact branching were also investigated. Results indicated that most of the MdIPT and MdCKX, and MdPIN1 genes were upregulated by 6-BA and decapitation treatment, but inhibited by Lovastatin, a compound that effectively suppresses axillary bud outgrowth induced by decapitation. These findings suggest that cytokinin biosynthesis is required for the activation of bud break and the export of auxin from buds in apple tree with intact primary shoot apex or decapitated apple tree. MdCKX8 and MdCKX10, however, exhibited little response to decapitation, but were significantly up-regulated by 6-BA and Lovastatin, a finding that warrants further investigation in order to understand their function in bud-outgrowth.
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http://dx.doi.org/10.1016/j.gene.2018.01.101DOI Listing
April 2018

Revealing critical mechanisms of BR-mediated apple nursery tree growth using iTRAQ-based proteomic analysis.

J Proteomics 2018 02 19;173:139-154. Epub 2017 Dec 19.

College of Horticulture, Northwest A & F University, Yangling, Shaanxi 712100, China. Electronic address:

Brassinosteroid is identified as an important hormone. However, information about brassinosteroid has not been fully elucidated, and few studies concerned its role in apple. The aim of this work was to study the role of brassinosteroid for apple tree growth. In our study, the effect of brassinosteroid on apple nursery tree was analyzed. The biomass, cell size and xylem content of apple nursery tree were obviously evaluated by brassinosteroid treatment; mineral elements contents, photosynthesis indexes, carbohydrate level and hormone contents were significantly high in brassinosteroid treated trees. To explore the molecular mechanisms of these phenotypic differences, iTRAQ-based quantitative proteomics were used to identify the expression profiles of proteins in apple nursery tree shoot tips in response to brassinosteroid at a key period (14days after brassinosteroid treatment). A total of 175 differentially expressed proteins were identified. They were mainly involved in chlorophyII biosynthesis, photosynthesis, carbohydrate metabolism, glycolysis, citric acid cycle, respiratory action, hormone signal, cell growth and ligin metabolism. The findings in this study indicate that brassinosteroid mediating apple nursery tree growth may be mainly through energy metabolism. Important biological processes identified here can be useful theoretical basis and provide new insights into the molecular mechanisms of brassinosteroid.

Biological Significance: Brassinosteroid is very important for plant growth and development. However, the molecular mechanism of brassinosteroid mediating growth process is not perfectly clear in plant, especially in apple nursery tree. We used a combination of physiological and bioinformatics analysis to investigate the effects of brassinosteroid on apple nursery tree growth and development. The data reported here demonstrated that brassinosteroid regulates apple nursery tree growth mainly through energy metabolism. Therefore it can provide a theoretical basis from energy points for developing dwarfed or compact apple trees. This will benefit for low orchard management cost as well as early bearing, and high fruit yield as well as quality.
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http://dx.doi.org/10.1016/j.jprot.2017.12.007DOI Listing
February 2018

Genome-wide analysis of carotenoid cleavage oxygenase genes and their responses to various phytohormones and abiotic stresses in apple (Malus domestica).

Plant Physiol Biochem 2018 Feb 5;123:81-93. Epub 2017 Dec 5.

College of Horticulture, Northwest A & F University, Yangling, Shaanxi, 712100, China. Electronic address:

Carotenoid cleavage oxygenases (CCOs) are able to cleave carotenoids to produce apocarotenoids and their derivatives, which are important for plant growth and development. In this study, 21 apple CCO genes were identified and divided into six groups based on their phylogenetic relationships. We further characterized the apple CCO genes in terms of chromosomal distribution, structure and the presence of cis-elements in the promoter. We also predicted the cellular localization of the encoded proteins. An analysis of the synteny within the apple genome revealed that tandem, segmental, and whole-genome duplication events likely contributed to the expansion of the apple carotenoid oxygenase gene family. An additional integrated synteny analysis identified orthologous carotenoid oxygenase genes between apple and Arabidopsis thaliana, which served as references for the functional analysis of the apple CCO genes. The net photosynthetic rate, transpiration rate, and stomatal conductance of leaves decreased, while leaf stomatal density increased under drought and saline conditions. Tissue-specific gene expression analyses revealed diverse spatiotemporal expression patterns. Finally, hormone and abiotic stress treatments indicated that many apple CCO genes are responsive to various phytohormones as well as drought and salinity stresses. The genome-wide identification of apple CCO genes and the analyses of their expression patterns described herein may provide a solid foundation for future studies examining the regulation and functions of this gene family.
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http://dx.doi.org/10.1016/j.plaphy.2017.12.001DOI Listing
February 2018

Autocrine parathyroid hormone-like hormone promotes intrahepatic cholangiocarcinoma cell proliferation via increased ERK/JNK-ATF2-cyclinD1 signaling.

J Transl Med 2017 Nov 25;15(1):238. Epub 2017 Nov 25.

Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou Avenue North, Baiyun District, Guangzhou, Guangdong, China.

Background And Aims: Intrahepatic cholangiocarcinoma (ICC) is an aggressive tumor with a high fatality rate. It was recently found that parathyroid hormone-like hormone (PTHLH) was frequently overexpressed in ICC compared with non-tumor tissue. This study aimed to elucidate the underlying mechanisms of PTHLH in ICC development.

Methods: The CCK-8 assay, colony formation assays, flow cytometry and a xenograft model were used to examine the role of PTHLH in ICC cells proliferation. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins. Luciferase reporter, chromatin immunoprecipitation (ChIP) and DNA pull-down assays were used to verify the transcription regulation of activating transcription factor-2 (ATF2).

Results: PTHLH was significantly upregulated in ICC compared with adjacent and normal tissues. Upregulation of PTHLH indicated a poor pathological differentiation and intrahepatic metastasis. Functional study demonstrated that PTHLH silencing markedly suppressed ICC cells growth, while specific overexpression of PTHLH has the opposite effect. Mechanistically, secreted PTHLH could promote ICC cell growth by activating extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and subsequently upregulated ATF2 and cyclinD1 expression. Further study found that the promoter activity of PTHLH were negatively regulated by ATF2, indicating that a negative feedback loop exists.

Conclusions: Our findings demonstrated that the ICC-secreted PTHLH plays a characteristic growth-promoting role through activating the canonical ERK/JNK-ATF2-cyclinD1 signaling pathways in ICC development. We identified a negative feedback loop formed by ATF2 and PTHLH. In this study, we explored the therapeutic implication for ICC patients.
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http://dx.doi.org/10.1186/s12967-017-1342-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702246PMC
November 2017

Comprehensive analysis of GASA family members in the Malus domestica genome: identification, characterization, and their expressions in response to apple flower induction.

BMC Genomics 2017 Oct 27;18(1):827. Epub 2017 Oct 27.

College of Horticulture, Northwest A&F University, Yangling, Shaanxi, 712100, People's Republic of China.

Background: The plant-specific gibberellic acid stimulated Arabidopsis (GASA) gene family is critical for plant development. However, little is known about these genes, particularly in fruit tree species.

Results: We identified 15 putative Arabidopsis thaliana GASA (AtGASA) and 26 apple GASA (MdGASA) genes. The identified genes were then characterized (e.g., chromosomal location, structure, and evolutionary relationships). All of the identified A. thaliana and apple GASA proteins included a conserved GASA domain and exhibited similar characteristics. Specifically, the MdGASA expression levels in various tissues and organs were analyzed based on an online gene expression profile and by qRT-PCR. These genes were more highly expressed in the leaves, buds, and fruits compared with the seeds, roots, and seedlings. MdGASA genes were also responsive to gibberellic acid (GA) and abscisic acid treatments. Additionally, transcriptome sequencing results revealed seven potential flowering-related MdGASA genes. We analyzed the expression levels of these genes in response to flowering-related treatments (GA, 6-benzylaminopurine, and sugar) and in apple varieties that differed in terms of flowering ('Nagafu No. 2' and 'Yanfu No. 6') during the flower induction period. These candidate MdGASA genes exhibited diverse expression patterns. The expression levels of six MdGASA genes were inhibited by GA, while the expression of one gene was up-regulated. Additionally, there were expression-level differences induced by the 6-benzylaminopurine and sugar treatments during the flower induction stage, as well as in the different flowering varieties.

Conclusion: This study represents the first comprehensive investigation of the A. thaliana and apple GASA gene families. Our data may provide useful clues for future studies and may support the hypotheses regarding the role of GASA proteins during the flower induction stage in fruit tree species.
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http://dx.doi.org/10.1186/s12864-017-4213-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658915PMC
October 2017
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