Impact of pretransplant T2DM on left ventricular deformation and myocardial perfusion in heart transplanted recipients: a 3.0 T cardiac magnetic resonance study.

BACKGROUND: Pretransplant type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular and all-cause mortality after heart transplant (HT), but the underlying causes of this association remain unclear. The purpose of this research was to examine the impact of T2DM on left ventricular (LV) myocardial deformation and myocardial perfusion following heart transplantation using cardiovascular magnetic resonance imaging. METHODS: We investigated thirty-one HT recipients with pretransplant T2DM [HT(DM+)], thirty-four HT recipients without pretransplant T2DM [HT(DM-)] and thirty-six controls. LV myocardial strains, including the global longitudinal, radial, and circumferential strain (GLS, GRS and GCS, respectively), were calculated and compared among groups, as were resting myocardial perfusion indices, which included time to peak myocardial signal intensity (TTM), maximum signal intensity (MaxSI), and Upslope. The relationships between LV strain parameters or perfusion indices and biochemical indicators were determined through Spearman's analysis. The impact of T2DM on LV strains in HT recipients was assessed using multivariable linear regression analyses with backward stepwise selection. RESULTS: In the HT(DM+) group, the LV GLS, GRS, and GCS exhibited significantly lower magnitudes than those in both the HT(DM-) and control groups. TTM was higher in the HT(DM+) group than in both the HT(DM-) and control groups, while no significant differences were observed among the groups regarding Upslope and MaxSI. There was a negative correlation between glycated hemoglobin and the magnitude of strains (longitudinal, r = - 0.399; radial, r = - 0.362; circumferential, r = - 0.389) (all P < 0.05), and a positive correlation with TTM (r = 0.485, P < 0.001). Regression analyses that included both pretransplant T2DM and perfusion indices revealed that pretransplant T2DM, rather than perfusion indices, was an independent determinant of LV strain (ß = longitudinal, - 0.508; radial, - 0.370; circumferential, - 0.371) (all P < 0.05). CONCLUSION: In heart transplant recipients, pretransplant T2DM has a detrimental effect on subclinical left ventricular systolic function and could potentially impact myocardial microcirculation following HT.

Genome-wide identification and expression analysis of the AUX/IAA gene family in turnip (Brassica rapa ssp. rapa).

BACKGROUND: Auxin/indoleacetic acid (AUX/IAA) genes encoding short-lived proteins participate in AUX signaling transduction and play crucial roles in plant growth and development. Although the AUX/IAA gene family has been identified in many plants, a systematic analysis of AUX/IAA genes in Brassica rapa ssp. rapa has not yet been reported. RESULTS: We performed a comprehensive genome-wide analysis and found 89 AUX/IAA genes in turnip based on the conserved AUX/IAA domain (pfam02309). Phylogenetic analysis of AUX/IAA genes from turnip, Arabidopsis, and cabbage revealed that these genes cluster into six subgroups (A1, A2, A3, A4, B1, and B2). The motif distribution was also conservative among the internal members of the clade. Enhanced yellow fluorescent protein (EYFP) signals of BrrIAA-EYFPs showed that BrrIAA members functioned as nucleoproteins. Moreover, transcriptional analysis revealed that the expression patterns of AUX/IAA genes in turnip were tissue-dependent. Because orthologs have similar biological functions and interaction networks in plant growth and development, BrrIAA66 in turnip possibly played a role in embryo axis formation, vascular development, lateral root formation, and floral organ development by interacting with BrrARF19 and BrrTIR1. CONCLUSION: These results provide a theoretical basis for further investigation of BrrAUX/IAA genes and lay the foundation for functional analysis of BrrIAA66 in turnip.

A Single Amino Acid Substitution in STKc_GSK3 Kinase Conferring Semispherical Grains and Its Implications for the Origin of Triticum sphaerococcum.

Six subspecies of hexaploid wheat (Triticum aestivum) have been identified, but the origin of Indian dwarf wheat (Triticum sphaerococcum), the only subspecies with round grains, is currently unknown. Here, we isolated the grain-shape gene Tasg-D1 in T sphaerococcum via positional cloning. Tasg-D1 encodes a Ser/Thr protein kinase glycogen synthase kinase3 (STKc_GSK3) that negatively regulates brassinosteroid signaling. Expression of TaSG-D1 and the mutant form Tasg-D1 in Arabidopsis (Arabidopsis thaliana) suggested that a single amino acid substitution in the Thr-283-Arg-284-Glu-285-Glu-286 domain of TaSG-D1 enhances protein stability in response to brassinosteroids, likely leading to formation of round grains in wheat. This gain-of-function mutation has pleiotropic effects on plant architecture and exhibits incomplete dominance. Haplotype analysis of 898 wheat accessions indicated that the origin of T sphaerococcum in ancient India involved at least two independent mutations of TaSG-D1 Our results demonstrate that modest genetic changes in a single gene can induce dramatic phenotypic changes.

Multiparametric cardiovascular magnetic resonance characteristics and dynamic changes in asymptomatic heart-transplanted patients.

OBJECTIVES: To describe the dynamic changes in cardiac deformation and tissue characteristics using cardiac magnetic resonance (CMR) in asymptomatic patients during 12 months after heart transplantation (HT). METHODS: From April 2020 to January 2021, 21 consecutive HT patients without clinical symptoms were included in this prospective study. Multiparametric CMR was performed at 3, 6, and 12 months after HT. Twenty-five healthy volunteers served as controls. RESULTS: During follow-up, a decline in left ventricular (LV) global radial strain (GRS) (p = 0.020) and right ventricular (RV) global longitudinal strain (GLS) (p < 0.001) and an increase in post-contrast T1 (p = 0.024) and T2 (p < 0.001) in asymptomatic HT patients occurred at 3 months, which normalized at 6 months postoperatively, compared with those in healthy controls. A decline in LVGLS (p < 0.001) and LV global circumferential strain (GCS) (p < 0.001) and an increase in native T1 (p < 0.001), T2 (p < 0.001), and extracellular volume (ECV) (p < 0.001) occurred at 3 months. Although most parameters improved gradually, LVGLS, native T1, and ECV remained abnormal compared with those in healthy controls at 12 months; only T2 and LVGCS were normalized at 6 months and 12 months, respectively. ECV was significantly correlated with LVGLS, LVGCS, and LVGRS. CONCLUSION: Cardiac deformation and tissue characteristics were abnormal early after HT, although the patients were clinically asymptomatic. The dynamic changes in CMR characteristics demonstrate a gradual recovery of myocardial injury associated with transplantation during the first 12 months after HT. KEY POINTS: • Multiparametric CMR can detect the dynamic changes of transplantation-associated myocardial injury. • Post-contrast T1, T2, LVGRS, and RVGLS values are normalized at 6 months after HT. • Native T1, ECV, and LVGLS values remain abnormal compared with those in healthy controls at 12 months after HT.

Ringlike late gadolinium enhancement provides incremental prognostic value in non-classical arrhythmogenic cardiomyopathy.

BACKGROUND: The 2019 arrhythmogenic right ventricular cardiomyopathy (ARVC) risk model has proved insufficient in the capability of predicting ventricular arrhythmia (VA) risk in non-classical arrhythmogenic cardiomyopathy (ACM). Furthermore, the prognostic value of ringlike late gadolinium enhancement (LGE) of the left ventricle in non-classical ACM remains unknown. We aimed to assess the incremental value of ringlike LGE over the 2019 ARVC risk model in predicting sustained VA in patients with non-classical ACM. METHODS: In this retrospective study, consecutive patients with non-classical ACM who underwent CMR from January 2011 to January 2022 were included. The pattern of LGE was categorized as no, non-ringlike, and ringlike LGE. The primary outcome was defined as the occurrence of sustained VA. Univariable and multivariable Cox regression analysis was used to evaluate the impact of LGE patterns on sustained VA and area under curve (AUC) was calculated for the incremental value of ringlike LGE. RESULTS: A total of 73 patients were collected in the final cohort (mean age, 39.3 ± 14.4 years, 51 male), of whom 10 (13.7%) had no LGE, 33 (45.2%) had non-ringlike LGE, and 30 (41.1%) had ringlike LGE. There was no statistically significant difference in the 5-year risk score among the three groups (P = 0.190). During a median follow-up of 34 (13-56) months, 34 (46.6%) patients experienced sustained VA, including 1 (10.0%), 13 (39.4%) and 20 (66.7%) of patients with no, non-ringlike and ringlike LGE, respectively. After multivariable adjustment, ringlike LGE remained independently associated with the presence of sustained VA (adjusted hazard ratio: 6.91, 95% confidence intervals: 1.89-54.60; P = 0.036). Adding ringlike LGE to the 2019 ARVC risk model showed significantly incremental prognostic value for sustained VA (AUC: 0.80 vs. 0.67; P = 0.024). CONCLUSION: Ringlike LGE provides independent and incremental prognostic value over the 2019 ARVC risk model in patients with non-classical ACM.

A single nucleotide deletion in the third exon of FT-D1 increases the spikelet number and delays heading date in wheat (Triticum aestivum L.).

The spikelet number and heading date are two crucial and correlated traits for yield in wheat. Here, a quantitative trait locus (QTL) analysis was conducted in F8 recombinant inbred lines (RILs) derived from crossing two common wheats with different spikelet numbers. A total of 15 stable QTL influencing total spikelet number (TSN) and heading date (HD) were detected. Notably, FT-D1, a well-known flowering time gene in wheat, was located within the finely mapped interval of a major QTL on 7DS (QTsn/Hd.cau-7D). A causal indel of one G in the third exon of FT-D1 was significantly associated with total spikelet number and heading date. Consistently, CRISPR/Cas9 mutant lines with homozygous mutations in FT-D1 displayed an increase in total spikelet number and heading date when compared with wild type. Moreover, one simple and robust marker developed according to the polymorphic site of FT-D1 revealed that this one G indel had been preferentially selected to adapt to different environments. Collectively, these data provide further insights into the genetic basis of spikelet number and heading date, and the diagnostic marker of FT-D1 will be useful for marker-assisted pyramiding in wheat breeding.

Heat Stress Tolerance 2 confers basal heat stress tolerance in allohexaploid wheat (Triticum aestivum L.).

Heat stress substantially reduces the yield potential of wheat (Triticum aestivum L.), one of the most widely cultivated staple crops, and greatly threatens global food security in the context of global warming. However, few studies have explored the heat stress tolerance (HST)-related genetic resources in wheat. Here, we identified and fine-mapped a wheat HST locus, TaHST2, which is indispensable for HST in both the vegetative and reproductive stages of the wheat life cycle. The studied pair of near isogenic lines (NILs) exhibited diverse morphologies under heat stress, based on which we mapped TaHST2 to a 485 kb interval on chromosome arm 4DS. Under heat stress, TaHST2 confers a superior conversion rate from soluble sugars to starch in wheat grains, resulting in faster grain filling and a higher yield potential. A further exploration of genetic resources indicated that TaHST2 underwent strong artificial selection during wheat domestication, suggesting it is an essential locus for basal HST in wheat. Our findings provide deeper insights into the genetic basis of wheat HST and might be useful for global efforts to breed heat-stress-tolerant cultivars.

Identification and characterization of QTL for spike morphological traits, plant height and heading date derived from the D genome of natural and resynthetic allohexaploid wheat.

KEY MESSAGE: QHd.cau-7D.1 for heading date was delimited into the physical interval of approximately 17.38 Mb harboring three CONSTANS-like zinc finger genes. Spike morphological traits, plant height and heading date play important roles in yield improvement of wheat. To reveal the genetic factors that controlling spike morphological traits, plant height and heading date on the D genome, we conducted analysis of quantitative traits locus (QTL) using 198 F7:8 recombinant inbred lines (RILs) derived from a cross between the common wheat TAA10 and resynthesized allohexaploid wheat XX329 with similar AABB genomes. A total of 23 environmentally stable QTL on the D sub-genome for spike length (SL), fertile spikelet number per spike (FSN), sterile spikelet number per spike (SSN), total spikelet number per spike (TSN), spike compactness (SC), plant height (PHT) and heading date (HD) were detected, among which eight appeared to be novel QTL. Furthermore, QHd.cau-7D.1 and QPht.cau-7D.2 shared identical confidence interval and were delimited into the physical interval of approximately 17.38 Mb with 145 annotated genes, including three CONSTANS-like zinc finger genes (TraesCS7D02G209000, TraesCS7D02G213000 and TraesCS7D02G220300). This study will help elucidate the molecular mechanism of the seven traits (SL, FSN, SSN, TSN, SC, PHT and HD) and provide a potentially valuable resource for genetic improvement.

Phenotypic characterization of the glossy1 mutant and fine mapping of GLOSSY1 in common wheat (Triticum aestivum L.).

KEY MESSAGE: A novel wax locus GLOSSY1 was finely mapped to an approximately 308.1-kbp genomic interval on chromosome 2DS of wheat. The epicuticular wax, the outermost layer of aerial organs, gives plants their bluish-white (glaucous) appearance. Epicuticular wax is ubiquitous and provides an essential protective function against environmental stresses. In this study, we identified the glossy1 mutant on the basis of its glossy glume from an EMS population in the elite wheat (Triticum aestivum L.) cultivar Jimai22. The mutant had a dramatically different profile in total wax load and composition of individual wax constituents relative to the wild type, resulting in the increased cuticle permeability of glumes. The glossy glume phenotype was controlled by a single, semidominant locus mapping to the short arm of chromosome 2D, within a 308.1-kbp genomic interval that contained ten annotated protein-coding genes. These results pave the way for an in-depth analysis of the underlying genetic basis of wax formation patterns and enrich our understanding of mechanisms regulating wax metabolism.

Overexpression of BpCUC2 Influences Leaf Shape and Internode Development in Betula pendula.

The CUP-SHAPED COTYLEDON 2 (CUC2) gene, which is negatively regulated by microRNA164 (miR164), has been specifically linked to the regulation of leaf margin serration and the maintenance of phyllotaxy in model plants. However, few studies have investigated these effects in woody plants. In this study, we integrated genomic, transcriptomic, and physiology approaches to explore the function of BpCUC2 gene in Betula pendula growth and development. Our results showed that Betula pendula plants overexpressing BpCUC2, which is targeted by BpmiR164, exhibit shortened internodes and abnormal leaf shapes. Subsequent analysis indicated that the short internodes of BpCUC2 overexpressed transgenic lines and were due to decreased epidermal cell size. Moreover, transcriptome analysis, yeast one-hybrid assays, and ChIP-PCR suggested that BpCUC2 directly binds to the LTRECOREATCOR15 (CCGAC), CAREOSREP1 (CAACTC), and BIHD1OS (TGTCA) motifs of a series of IAA-related and cyclin-related genes to regulate expression. These results may be useful to our understanding of the functional role and genetic regulation of BpCUC2.

Transcriptome analysis reveals potential mechanisms for different grain size between natural and resynthesized allohexaploid wheats with near-identical AABB genomes.

BACKGROUND: Common wheat is a typical allohexaploid species (AABBDD) derived from the interspecific crossing between allotetraploid wheat (AABB) and Aegilops tauschii (DD). Wide variation in grain size and shape observed among Aegilops tauschii can be retained in synthetic allohexaploid wheats, but the underlying mechanism remains enigmatic. Here, the natural and resynthesized allohexaploid wheats with near-identical AB genomes and different D genomes (TAA10 and XX329) were employed for analysis. RESULTS: Significant differences in grain size and weight between TAA10 and XX329 were observed at the early stages of development, which could be mainly attributed to the higher growth rates of the pericarp and endosperm cells in XX329 compared to TAA10. Furthermore, comparative transcriptome analysis identified that 8891 of 69,711 unigenes (12.75%) were differentially expressed between grains at 6 days after pollination (DAP) of TAA10 and XX329, including 5314 up-regulated and 3577 down-regulated genes in XX329 compared to TAA10. The MapMan functional annotation and enrichment analysis revealed that the differentially expressed genes were significantly enriched in categories of cell wall, carbohydrate and hormone metabolism. Notably, consistent with the up-regulation of sucrose synthase genes in resynthesized relative to natural allohexaploid wheat, the resynthesized allohexaploid wheat accumulated much higher contents of glucose and fructose in 6-DAP grains than those of the natural allohexaploid wheat. CONCLUSIONS: These data indicated that the genetic variation of the D genome induced drastic alterations of gene expression in grains of the natural and resynthesized allohexaploid wheats, which may contribute to the observed differences in grain size and weight.

Overexpression of BpAP1 induces early flowering and produces dwarfism in Betula platyphylla × Betula pendula.

The involvement of APETALA1 (AP1) in the flowering transition has been the focus of much research. Here, we produced Betula platyphylla × Betula pendula (birch) lines that overexpressed BpAP1 using Agrobacterium-mediated transformation; we obtained five independent 35S::BpAP1 transgenic lines. Polymerase chain reaction (PCR), Southern, northern and western analyses were used to identify the transformants. As determined by quantitative real-time PCR (qRT-PCR), BpAP1 expression in roots, shoots, leaves and terminal buds of 35S::BpAP1 transgenic lines was significantly higher than that in the wild type (WT, P < 0.01). The average height of 2-year-old 35S::BpAP1 plants was significantly lower (41.17%) than that of non-transgenic plants. In the 35S::BpAP1 lines, inflorescences emerged successively beginning 2 months after transplanting. In addition, the length-diameter ratio of fully developed male and female inflorescences were both significantly less than those of the WT (P < 0.05), i.e. the morphological characteristic was stubby. The male inflorescences emerged early, with empty, draped anthers, and pollen was rarely produced, whereas the female floret structure was not different from WT. The pistils developed normally and could accept pollen, leading to the production of hybrid progeny (F1 ). F1 plants completed flowering within only 1 year after sowing. We demonstrate that BpAP1 can be inherited through sexual reproduction. Overexpression of BpAP1 caused early flowering and dwarfism; these lines had an obviously shortened juvenile phase. These results greatly increase our understanding of the mechanisms underlying the flowering transition and enhance genetic studies of birch traits, and they open up new possibilities for the breeding of birch and other woody plants.

DNA tetrahedral scaffold-corbelled 3D DNAzyme walker for electrochemiluminescent aflatoxin B1 detection.

The reaction efficiency of surface-based DNA walker can directly affect the properties of a biosensor. Herein, three-dimensional (3D) DNAzyme walker were first fixed on the top of DNA tetrahedral scaffold to improve the immobilization efficiency. Ferrocene (Fc) that labeled at substrate strand ends effectively quenched the electrochemiluminescence (ECL) signal of Ru(bpy)2(cpaphen)2+, yielding the sensor in a "signal-off" state. Upon the addition of aflatoxin B1 (AFB1), 3D DNAzyme walker was activated and fueled by Na+, accordingly releasing Fc and recovering the ECL signal of Ru(bpy)2(cpaphen)2+. Due to the high movement efficiency of such 3D DNAzyme walker, ultrasensitive detection of AFB1 was achieved in the range of 1.0 fg mL-1-10 ng mL-1, with a detection limit of 0.58 fg mL-1. Moreover, satisfactory results were obtained while detecting AFB1 in corn and peanut samples, suggesting it has a potential application in food safety analysis.

Two-step förster resonance energy transfer amplification for ratiometric detection of pathogenic bacteria in food samples.

We described a two-step förster resonance energy transfer (FRET) system for ratiometric Staphylococcus aureus (S. aureus) detection based on a dual-recognition proximity binding-induced toehold strand displacement reactions (TSDR). Ru(bpy)32+ and platinum nanoparticles (Pt NPs) labeled DNA (Ru-S3 and Pt NPs-S4) hybridized to enable the occurrence of the primary FRET using Ru(bpy)32+ as the energy donor and Pt NPs as the energy acceptor. TSDR happened by integrating vancomycin hydrochloride labeled S1 (Van-S1) and gold nanoclusters labeled S2-aptamer (Au NCs-S2-aptamer) with S. aureus. The single DNA segments of Van-S1 bond to the terminal toehold of Ru-S3, displacing Pt-S4, inducing the secondary FRET using Au NCs as the energy donor and Ru(bpy)32+ as the energy acceptor. This two-step FRET system efficiently improved the reaction efficiency of S. aureus with a detection limit of 1.0 CFU/mL. Furthermore, satisfactory results obtained while detecting S. aureus in food samples, indicating a great potential for food analysis.

Zettomole electrochemical HIV DNA detection using 2D DNA-Au nanowire structure, hemin/G-quadruplex and polymerase chain reaction multi-signal synergistic amplification.

Multi-signal synergistically amplified electrochemical sensing of HIV DNA was proposed based on two-dimensional (2D) DNA-Au nanowire structure coupled with hemin/G-quadruplex and polymerase chain reaction (PCR). In the design, by using target HIV DNA as the template, PCR generated numbers of double-stranded DNA (dsDNA) with free single-stranded DNA (ssDNA) tails on one side and free G-quadruplex sequences on the other side. Then, the ssDNA tails of the PCR products were hybridized with the capture probe (CP) to introduce the hemin/G-quadruplex to the electrode surface as a redox-active reporter and to amplify the electrochemical signal as mimic peroxidase catalysis in the presence of H2O2. Meanwhile, (+)AuNPs were electrostatically adsorbed onto dsDNA surface for the formation of 2D DNA-Au nanowire structure, amplifying the electrochemical signal further as another mimic peroxidase and electric conductor together. By effectively combining these signal amplification processes, ultrasensitive HIV DNA detection was achieved with a detection limit of 1.3 aM, indicating that it has potential application in clinical diagnosis.

Identification of QTL for Grain Size and Shape on the D Genome of Natural and Synthetic Allohexaploid Wheats with Near-Identical AABB Genomes.

Grain size and shape associated with yield and milling quality are important traits in wheat domestication and breeding. To reveal the genetic factors on the D genome that control grain size and shape variation, we conducted analysis of quantitative trait loci (QTL) using the F2 and F2:3 populations derived from a common allohexaploid wheat line TAA10 and a synthetic allohexaploid wheat XX329, which have near-identical AABB genomes and different DD genomes. Based on genotyping using wheat 660K single nucleotide polymorphism (SNP) array, TAA10 and XX329 exhibited 96.55, 98.10, and 66.26% genetic similarities of A, B, and D genomes, respectively. Phenotypic evaluation revealed that XX329 had higher thousand grain weight (TGW), grain length, width, area and perimeter than TAA10 across all environments, and the grain yield per plot of XX329 increased by 17.43-30.36% compared with that of TAA10 in two environments. A total of nine environmentally stable QTL associated with grain size and shape were mapped on chromosomes 2D and 7D and verified using near isogenic lines (NILs), with the synthetic allohexaploid wheat XX329 contributing favorable alleles. Notably, a novel QTL QTgw.cau-2D controlling grain weight was first identified from the synthetic allohexaploid wheat, which may be a more desirable target for genetic improvement in wheat breeding. Collectively, these results provide further insights into the genetic factors that shaped the grain morphology during wheat evolution and domestication.