YBX1 inhibits mitochondrial-mediated apoptosis in ischemic heart through the PI3K/AKT signaling pathway

Background:Myocardial infarction(MI)is associated with higher morbidity and mortality in the world,especially in cold weather.YBX1 is an RNA-binding protein that is required for pathological growth of cardiomyocyte by regulating cell growth and protein synthesis.But YBX1,as an individual RNA-binding protein,regulates cardiomyocytes through signaling cascades during myocardial infarction remain largely unexplored.Methods:In vivo,the mouse MI model was induced by ligating the left anterior descending coronary artery(LAD),and randomly divided into sham operation group,MI group,MI+YBX1 knockdown/overexpression group and MI+negative control(NC)group.The protective effect of YBX1 was verified by echocardiography and triphenyltetrazolium chloride staining.In vitro,mitochondrial-dependent apoptosis was investigated by using CCK8,TUNEL staining,reactive oxygen species(ROS)staining and JC-1 staining in hypoxic neonatal mouse cardiomyocytes(NMCMs).Results:YBX1 expression of cardiomyocytes was downregulated in a mouse model and a cellular model on the ischemic condition.Compared to mice induced by MI,YBX1 overexpression mediated by adeno-associated virus serotype 9(AAV9)vector reduced the infarcted size and improved cardiac function.Knockdown of endogenous YBX1 by shRNA partially aggravated ischemia-induced cardiac dysfunction.In hypoxic cardiomyocytes,YBX1 overexpression decreased lactic dehydrogenase(LDH)release,increased cell viability,and inhibited apoptosis by affecting the expression of apoptosis related proteins,while knockdown of endogenous YBX1 by siRNA had the opposite effect.Overexpression of YBX1 restored mitochondrial dysfunction in hypoxic NMCMs by increasing mitochondrial membrane potential and ATP content and decreasing ROS.In hypoxic NMCMs,YBX1 overexpression increased the expression of phosphorylated phosphatidylinositol 3 kinase(PI3K)/AKT,and the anti-apoptosis effect of YBX1 was eliminated t by LY294002,PI3K/AKT inhibitor.Conclusion:YBX1 protected the heart from ischemic damage by inhibiting the mitochondrial-dependent apoptosis through PI3K/AKT pathway.It is anticipated that YBX1 may serve as a novel therapeutic target for MI.

Influence of CdS films synthesized by different methods on the photovoltaic performance of CdTe/CdS thin film solar cells

The cadmium sulphide (CdS) film is grown on cadmium telluride (CdTe) nanorods (NRs) arrays by different methods such as chemical bath deposition (CBD), magnetron sputtering (MS), and homogenous precipitation (HP) techniques. The impact of various deposition methods is explored in detail on the growth of CdTe/CdS composite film, the CdTe/CdS interface property, and solar cell efficiency. Compared to the CBD and HP methods, the MS method can improve the growth of the CdS on CdTe NRs with high crystalline quality. The device based on the CdS film prepared by the MS method demonstrates excellent photovoltaic performance, which has the potential for applications in solar cells.

Centromere repositioning and shifts in wheat evolution

The centromere is the region of a chromosome that directs its separation and plays an important role in cell division and reproduction of organisms.Elucidating the dynamics of centromeres is an alternative strategy for exploring the evolution of wheat.Here,we comprehensively analyzed centromeres from the de novoassembled common wheat cultivar Aikang58(AK58),Chinese Spring(CS),and all sequenced diploid and tetraploid ancestors by chromatin immunoprecipitation sequencing,whole-genome bisulfite sequencing,RNA sequencing,assay for transposase-accessible chromatin using sequencing,and comparative genomics.We found that centromere-associated sequences were concentrated during tetraploidization and hexaploidization.Centromeric repeats of wheat(CRWs)have undergone expansion during wheat evolution,with strong interweaving between the A and B subgenomes post tetraploidization.We found that CENH3 prefers to bind with younger CRWs,as directly supported by immunocolocalization on two chromosomes(1A and 2A)of wild emmer wheat with dicentromeric regions,only one of which bound with CENH3.In a comparison of AK58 with CS,obvious centromere repositioning was detected on chromosomes 1B,3D,and 4D.The active centromeres showed a unique combination of lower CG but higher CHH and CHG methylation levels.We also found that centromeric chromatin was more open than pericentromeric chromatin,with higher levels of gene expression but lower gene density.Frequent introgression between tetraploid and hexaploid wheat also had a strong influence on centromere position on the same chromosome.This study also showed that active wheat centromeres were genetically and epigenetically determined.

Resequencing of 145 Landmark Cultivars Reveals Asymmetric Sub-genome Selection and Strong Founder Genotype Effects on Wheat Breeding in China

Controlled pedigrees and the multi-decade timescale of national crop plant breeding programs offer a unique experimental context for examining how selection affects plant genomes.More than 3000 wheat cultivars have been registered,released,and documented since 1949 in China.In this study,a set of 145 elite cultivars selected from historical points of wheat breeding in China were re-sequenced.A total of 43.75 Tb of sequence data were generated with an average read depth of 17.94x for each cultivar,and more than 60.92 million SNPs and 2.54 million InDels were captured,based on the Chinese Spring RefSeq genome v1.0.Seventy years of breeder-driven selection led to dramatic changes in grain yield and related phenotypes,with distinct genomic regions and phenotypes tar-geted by different breeders across the decades.There are very clear instances illustrating how introduced Italian and otherforeign germplasm was integrated into Chinese wheat programs and reshaped the genomic landscape of local modern cultivars.Importantly,the resequencing data also highlighted significant asymmetric breeding selec-tion among the three sub-genomes:this was evident in both the collinear blocks for homeologous chromosomes and among sets of three homeologous genes.Accumulation of more newly assembled genes in newer cultivars implied the potential value of these genes in breeding.Conserved and extended sharing of linkage disequilibrium(LD)blocks was highlighted among pedigree-related cultivars,in which fewer haplotype differences were detected.Fixation or replacement of haplotypes from founder genotypes after generations of breeding was related to their breeding value.Based on the haplotype frequency changes in LD blocks of pedigree-related cultivars,we propose a strategy for evaluating the breeding value of any given line on the basis of the accumulation(pyramiding)of bene-ficial haplotypes.Collectively,our study demonstrates the influence of "founder genotypes" on the output of breeding efforts over many decades and also suggests that founder genotype perspectives are in fact more dy-namic when applied in the context of modern genomics-informed breeding.

A haplotype block associated with thousand-kernel weight on chromosome 5DS in common wheat(Triticum aestivum L.)

Spike number per unit area, number of grains per spike, and thousand-kernel weight（TKW） are important yield components for wheat（Triticum aestivum L.）. TKW has the highest heritability among the three components. We validated 27 simple sequence repeat（SSR） loci associated with TKW in an F2：5breeding population grown in four environments. A cfd78265 bpmarker on chromosome 5DS showed the strongest association with TKW and had a significantly positive effect on TKW compared to allele cfd78259 bp, with mean increases of 5.17, 3.63, 4.11, and 5.16 g in the four environments. Markers cfd67 and cfd40 flanking cfd78 also showed significantly positive associations with TKW with increases of 5.11, 3.29, 4.31, and 4.50 g for cfd67205, and4.98, 3.49, 4.06, and 4.84 g for cfd40187 compared with cfd67203 and cfd40190in the four environments, respectively. A major quantitative trait locus for TKW spanning 2.94 c M on chromosome 5DS was detected by association mapping.Strong linkage disequilibrium（LD）（r2〉 0.2） was detected Resear among the three linked markers, which formed three haplotype blocks in the F2：5breeding population. Mean TKW differences between Hap B-I and Hap B-II were 5.80, 4.41, 4.02,and 5.06 g in the four environments, respectively. Moreover,significant LD was detected only between cfd78 and cfd67 and between cfd67 and cfd40 in a germplasm collection. This study provides a base for cloning genes related to TKW on chromosome 5DS.