ABSTRACT
Garlic, an asexually propagated crop, is the second important bulb crop after the onion and is used as a vegetable and medicinal plant. Abundant and diverse garlic resources have been formed over thousands of years of cultivation. However, genome variation, population structure and genetic architecture of garlic agronomic traits were still not well elucidated. Here, 1 100 258 single nucleotide polymorphisms (SNPs) were identified using genotyping-by-sequencing in 606 garlic accessions collected from 43 countries. Population structure, principal component and phylogenetic analysis showed that these accessions were divided into five subpopulations. Twenty agronomic traits, including above-ground growth traits, bulb-related and bolt-related traits in two consecutive years were implemented in a genome-wide association study. In total, 542 SNPs were associated with these agronomic traits, among which 188 SNPs were repeatedly associated with more than two traits. One SNP (chr6: 1896135972) was repeatedly associated with ten traits. These associated SNPs were located within or near 858 genes, 56 of which were transcription factors. Interestingly, one non-synonymous SNP (Chr4: 166524085) in ribosomal protein S5 was repeatedly associated with above-ground growth and bulb-related traits. Additionally, gene ontology enrichment analysis of candidate genes for genomic selection regions between complete-bolting and non-bolting accessions showed that these genes were significantly enriched in 'vegetative to reproductive phase transition of meristem', 'shoot system development', 'reproductive process', etc. These results provide valuable information for the reliable and efficient selection of candidate genes to achieve garlic genetic improvement and superior varieties.
ABSTRACT
Photoimmunotherapy has been acknowledged to be an unprecedented strategy to obtain significantly improved cancer treatment efficacy. In this regard, the exploitation of high-performance multimodal phototheranostic agents is highly desired. Apart from tailoring electron donors, acceptor engineering is gradually rising as a deliberate approach in this field. Herein, we rationally designed a family of aggregation-induced emission (AIE)-active compounds with the same donors but different acceptors based on the acceptor engineering. Through finely adjusting the functional groups on electron acceptors, the electron affinity of electron acceptors and the conformation of the compounds were simultaneously modulated. It was found that one of the molecules (named DCTIC), bearing a moderately electrophilic electron acceptor and the best planarity, exhibited optimal phototheranostic properties in terms of light-harvesting ability, fluorescence emission, reactive oxygen species (ROS) production, and photothermal performance. For the purpose of amplified therapeutic outcomes, DCTIC was fabricated into tumor and mitochondria dual-targeted DCTIC nanoparticles (NPs), which afforded good performance in the fluorescence/photoacoustic/photothermal trimodal imaging-guided photodynamic/photothermal-synergized cancer immunotherapy with the combination of programmed cell death protein-1 (PD-1) antibody. Not only the primary tumors were totally eradicated, but efficient growth inhibition of distant tumors was also realized.
Subject(s)
Nanoparticles , Neoplasms , Photochemotherapy , Humans , Phototherapy , Neoplasms/diagnostic imaging , Neoplasms/therapy , Immunotherapy , Mitochondria , Theranostic Nanomedicine , Oxidants , Multimodal Imaging , Cell Line, TumorABSTRACT
From highly aligned extracellular fibrils to the cells, a multilevel ordered hierarchy in valve leaflets is crucial for their biological function. Cardiac valve pathology most frequently involves a disruption in normal structure-function correlations through abnormal and complex interaction of cells, extracellular matrix, and their environment. At present, effective treatment for valve disease is limited and frequently ends with surgical repair or replacement with a mechanical or artificial biological cardiac valve, which comes with insuperable complications for many high-risk patients including aged and pediatric populations. Therefore, there is a critical need to fully appreciate the pathobiology of valve disease in order to develop better, alternative therapies. To date, the majority of studies have focused on delineating valve disease mechanisms at the cellular level. However, the cellular heterogeneity and function is still unclear. In this review, we summarize the body of work on valve cells, with a particular focus on the discoveries about valve cells heterogeneity and functions using single-cell RNA sequencing. We conclude by discussing state-of-the-art strategies for deciphering heterogeneity of these complex cell types, and argue this knowledge could translate into the improved personalized treatment of cardiac valve disease.
Subject(s)
Heart Valve Diseases , Heart Valve Prosthesis , Child , Humans , Aged , Heart Valve Diseases/surgery , Heart Valves , Sequence Analysis, RNA , BiologyABSTRACT
BACKGROUND: The nuclear receptor Rev-erbα/ß, a key component of the circadian clock, emerges as a drug target for heart diseases, but the function of cardiac Rev-erb has not been studied in vivo. Circadian disruption is implicated in heart diseases, but it is unknown whether cardiac molecular clock dysfunction is associated with the progression of any naturally occurring human heart diseases. Obesity paradox refers to the seemingly protective role of obesity for heart failure, but the mechanism is unclear. METHODS: We generated mouse lines with cardiac-specific Rev-erbα/ß knockout (KO), characterized cardiac phenotype, conducted multi-omics (RNA-sequencing, chromatin immunoprecipitation sequencing, proteomics, and metabolomics) analyses, and performed dietary and pharmacological rescue experiments to assess the time-of-the-day effects. We compared the temporal pattern of cardiac clock gene expression with the cardiac dilation severity in failing human hearts. RESULTS: KO mice display progressive dilated cardiomyopathy and lethal heart failure. Inducible ablation of Rev-erbα/ß in adult hearts causes similar phenotypes. Impaired fatty acid oxidation in the KO myocardium, in particular, in the light cycle, precedes contractile dysfunctions with a reciprocal overreliance on carbohydrate utilization, in particular, in the dark cycle. Increasing dietary lipid or sugar supply in the dark cycle does not affect cardiac dysfunctions in KO mice. However, obesity coupled with systemic insulin resistance paradoxically ameliorates cardiac dysfunctions in KO mice, associated with rescued expression of lipid oxidation genes only in the light cycle in phase with increased fatty acid availability from adipose lipolysis. Inhibition of glycolysis in the light cycle and lipid oxidation in the dark cycle, but not vice versa, ameliorate cardiac dysfunctions in KO mice. Altered temporal patterns of cardiac Rev-erb gene expression correlate with the cardiac dilation severity in human hearts with dilated cardiomyopathy. CONCLUSIONS: The study delineates temporal coordination between clock-mediated anticipation and nutrient-induced response in myocardial metabolism at multi-omics levels. The obesity paradox is attributable to increased cardiac lipid supply from adipose lipolysis in the fasting cycle due to systemic insulin resistance and adiposity. Cardiac molecular chronotypes may be involved in human dilated cardiomyopathy. Myocardial bioenergetics downstream of Rev-erb may be a chronotherapy target in treating heart failure and dilated cardiomyopathy.
Subject(s)
Circadian Rhythm/physiology , Myocardium/pathology , Obesity/physiopathology , Animals , Circadian Clocks , Heart Diseases , Humans , Mice , Mice, KnockoutABSTRACT
Garlic (Allium sativum L.) is an economically important vegetable crop which is used worldwide for culinary and medicinal purposes. Soil salinity constrains the yield components of garlic. Understanding the responsive mechanism of garlic to salinity is crucial to improve its tolerance. To address this problem, two garlic cultivars differing in salt tolerance were used to investigate the long-term adaptive responses to salt stress at phenotype and transcriptome levels. Phenotypic analysis showed four-week salt stress significantly decreased the yield components of salt-sensitive cultivar. Transcriptomes of garlics were de novo assembled and mined for transcriptional activities regulated by salt stress. The results showed that photosynthesis, energy allocation, and secondary metabolism were commonly enriched in both sensitive and tolerant genotypes. Moreover, distinct responsive patterns were also observed between the two genotypes. Compared with the salt-tolerant genotype, most transcripts encoding enzymes in the phenylpropanoid biosynthesis pathway were coordinately down regulated in the salt-sensitive genotype, resulting in alternation of the content and composition of lignin. Meanwhile, transcripts encoding the enzymes in the brassinosteroid (BR) biosynthesis pathway were also systematically down regulated in the salt-sensitive genotypes. Taken together, these results suggested that BR-mediated lignin accumulation possibly plays an important role in garlic adaption to salt stress. These findings expand the understanding of responsive mechanism of garlic to salt stress.
Subject(s)
Brassinosteroids/chemistry , Garlic/physiology , Lignin/chemistry , Salt Stress , Stress, Physiological , Transcriptome , Garlic/genetics , Gene Expression Profiling , Gene Expression Regulation, Plant , GenotypeABSTRACT
High callus production is a feasible way to improve the propagation coefficient of garlic. It remains unknown how genotypes and explants affect garlic callus formation. In the present investigation, we found that there were significant differences in callus formation among garlic varieties. Tip explants were the best calli-producing source, and 91.05% of the explants from four varieties, on average, formed calli after 45 d of primary culturing. Upper leaf parts explants produced lower values. Among the different varieties and explant types, tip explants of variety T141 induced calli in the shortest time and had the greatest callus fresh weight at 45 d. An endogenous hormone contents analysis showed that auxins (indole-3-acetic acid and methyl indole-3-acetic acetate), cytokinins (trans-zeatin and dihydrozeatin), gibberellins4, 9,15,19,24 and 53, abscisic acid, jasmonic acid, jasmonoyl-L-isoleucine, and dihydrojasmonic acid were significantly greater in the tips than those in the upper leaf parts. High endogenous jasmonic acid content might play important roles in callus formation. These results will help us not only establish an efficient garlic callus induction protocol that can be applied to large-scale callus multiplication and regeneration, and to genetically improvement of garlic production, but also understand endogenous hormone roles in tissue/organ differentiation and dedifferentiation.
Subject(s)
Garlic/growth & development , Garlic/genetics , Plant Growth Regulators/metabolism , Abscisic Acid/metabolism , Cytokinins/metabolism , Garlic/metabolism , Genotype , Gibberellins/metabolism , Indoleacetic Acids/metabolism , Organ Specificity , Plant Leaves/genetics , Plant Leaves/growth & development , Plant Leaves/metabolism , Primary Cell Culture/methodsABSTRACT
BACKGROUND: Garlic is the second largest allium crop after onion and is grown all over the world. The onion maggot (Delia antiqua M.) is a pest that seriously affects the yield and quality of garlic. Cultural controls and insecticides have several potential problems, including pesticide residue and development of resistance. Screening resistant varieties is an ideal alternative method. RESULTS: The resistance of 213 accessions of garlic clones against onion maggot was identified. The results showed that the pest index was between 5.56% and 91.11%, with classification into six groups by cluster analysis: HR (highly resistant), R (resistant), MR (moderately resistant), MS (moderately susceptible), S (susceptible) and HS (highly susceptible). Among these accessions, 9 and 30 were HR and R to onion maggot, respectively. Comparing the resistances of seven pairs of accessions between the original accessions and their progenies showed that single bulb clonal selection could be an effective way to improve allicin content, onion maggot resistance and most morphological traits. The relationship between allicin content and resistance was investigated, and a significant positive relationship was found. Accessions with a high content of allicin have great potential as resistant accessions. CONCLUSION: This study showed significant differences among garlic germplasm in their response to Delia antiqua M. Some accessions were highly resistant and tolerant. Utilization of these accessions will help minimize environmental pollution, preserve agro-ecosystems and biodiversity, and make management processes more economical. Furthermore, these accessions could be used in breeding programs to develop new maggot-resistant onion cultivars. © 2019 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Subject(s)
Antibiosis , Diptera/physiology , Garlic/physiology , Selection, Genetic , Sulfinic Acids/analysis , Animals , Diptera/growth & development , Disulfides , Larva/growth & development , Larva/physiologyABSTRACT
BACKGROUND: Garlic is one of the most important bulb vegetables and is mainly used as a spice or flavoring agent for foods. It is also cultivated for its medicinal properties, attributable to sulfur compounds, of which allicin is the most important. However, the stability of allicin in garlic extract is not well understood. In this study, using UPLC, the stability of allicin extracted in water from garlic was evaluated in phosphate buffer at different temperatures under light and dark conditions. RESULTS: At room temperature, allicin in aqueous extract was most stable at pH 5-6 but degraded quickly at lower or higher pH. It began to degrade within 0.5 h and was not detectable after 2 h when the pH was higher than 11 or lower than 1.5. It degraded quickly when the temperature was higher than 40 °C and especially higher than 70 °C. At room temperature, allicin in water could be stored for 5 days without obvious degradation. Higher concentrations of allicin in solution were somewhat more stable than low concentrations. CONCLUSION: Allicin extract was sensitive to pH and temperature of storage but not to light. Higher-concentration allicin solution was more stable.