Whole-genome sequencing of a worldwide collection of sugarcane cultivars (Saccharum spp.) reveals the genetic basis of cultivar improvement.

Sugarcane is the main source of sugar worldwide, and 80% of the sucrose production comes from sugarcane. However, the genetic differentiation and basis of agronomic traits remain obscure. Here, we sequenced the whole-genome of 219 elite worldwide sugarcane cultivar accessions. A total of approximately 6 million high-quality genome-wide single nucleotide polymorphisms (SNPs) were detected. A genome-wide association study identified a total of 2198 SNPs that were significantly associated with sucrose content, stalk number, plant height, stalk diameter, cane yield, and sugar yield. We observed homozygous tendency of favor alleles of these loci, and over 80% of cultivar accessions carried the favor alleles of the SNPs or haplotypes associated with sucrose content. Gene introgression analysis showed that the number of chromosome segments from Saccharum spontaneum decreased with the breeding time of cultivars, while those from S. officinarum increased in recent cultivars. A series of selection signatures were identified in sugarcane improvement procession, of which 104 were simultaneously associated with agronomic traits and 45 of them were mainly associated with sucrose content. We further proposed that as per sugarcane transgenic experiments, ShN/AINV3.1 plays a positive role in increasing stalk number, plant height, and stalk diameter. These findings provide comprehensive resources for understanding the genetic basis of agronomic traits and will be beneficial to germplasm innovation, screening molecular markers, and future sugarcane cultivar improvement.

Genome-wide identification and expression analysis of the cyclic nucleotide-gated ion channel (CNGC) gene family in Saccharum spontaneum.

BACKGROUND: Cyclic nucleotide-gated ion channels (CNGCs) are nonselective cation channels that are ubiquitous in eukaryotic organisms. As Ca2+ channels, some CNGCs have also proven to be K+-permeable and involved in plant development and responses to environmental stimuli. Sugarcane is an important sugar and energy crop worldwide. However, reports on CNGC genes in sugarcane are limited. RESULTS: In this study, 16 CNGC genes and their alleles were identified from Saccharum spontaneum and classified into 5 groups based on phylogenetic analysis. Investigation of gene duplication and syntenic relationships between S. spontaneum and both rice and Arabidopsis demonstrated that the CNGC gene family in S. spontaneum expanded primarily by segmental duplication events. Many SsCNGCs showed variable expression during growth and development as well as in tissues, suggesting functional divergence. Light-responsive cis-acting elements were discovered in the promoters of all the identified SsCNGCs, and the expression of most of the SsCNGCs showed a diurnal rhythm. In sugarcane, the expression of some SsCNGCs was regulated by low-K+ treatment. Notably, SsCNGC13 may be involved in both sugarcane development and its response to environmental stimuli, including response to low-K+ stress. CONCLUSION: This study identified the CNGC genes in S. spontaneum and provided insights into the transcriptional regulation of these SsCNGCs during development, circadian rhythm and under low-K+ stress. These findings lay a theoretical foundation for future investigations of the CNGC gene family in sugarcane.

Upgrading the genome of an elite japonica rice variety Kongyu 131 for lodging resistance improvement.

Developing a new rice variety requires tremendous efforts and years of input. To improve the defect traits of the excellent varieties becomes more cost and time efficient than breeding a completely new variety. Kongyu 131 is a high-performing japonica variety with early maturity, high yield, wide adaptability and cold resistance, but the poor-lodging resistance hinders the industrial production of Kongyu 131 in the Northeastern China. In this study, we attempted to improve the lodging resistance of Kongyu 131 from perspectives of both gene and trait. On the one hand, by QTL analysis and fine mapping we discovered the candidate gene loci. The following CRISPR/Cas9 and transgenic complementation study confirmed that Sd1 dominated the lodging resistance and favourable allele was mined for precise introduction and improvement. On the other hand, the Sd1 allelic variant was identified in Kongyu 131 by sequence alignment, then introduced another excellent allelic variation by backcrossing. Then, the two new resulting Kongyu 131 went through the field evaluation under different environments, planting densities and nitrogen fertilizer conditions. The results showed that the plant height of upgraded Kongyu 131 was 17%-26% lower than Kongyu 131 without penalty in yield. This study demonstrated a precise and targeted way to update the rice genome and upgrade the elite rice varieties by improving only a few gene defects from the perspective of breeding.

Genome-wide identification and transcriptional analysis of ammonium transporters in Saccharum.

Ammonium transporters (AMTs) are plasma membrane proteins that exclusively transport ammonium/ammonia. It is essential for the nitrogen demand of plantsby AMT-mediated acquisition of ammonium from soils. The molecular characteristics and evolutionary history of AMTs in Saccharum spp. remain unclear. We comprehensively evaluated the AMT gene family in the latest release of the S. spontaneum genome and identified 6 novel AMT genes. These genes belong to 3 clusters: AMT2 (2 genes), AMT3 (3 genes), and AMT4 (one gene). Evolutionary analyses suggested that the S. spontaneum AMT gene family may have expanded via whole-genome duplication events. All of the 6 AMT genes are located on 5 chromosomes of S. spontaneum. Expression analyses revealed that AMT3;2 was highly expressed in leaves and in the daytime, and AMT2;1/3;2/4 were dynamic expressed in different leaf segments, as well as AMT2;1/3;2 demonstrated a high transcript accumulation level in leaves and roots and were significantly dynamic expressed under low-nitrogen conditions. The results suggest the functional roles of AMT genes on tissue expression and ammonium absorption in Saccharum. This study will provide some reference information for further elucidation of the functional mechanism and regulation of expression of the AMT gene family in Saccharum.

Comparative phylogenetic analysis of CBL reveals the gene family evolution and functional divergence in Saccharum spontaneum.

BACKGROUND: The identification and functional analysis of genes that improve tolerance to low potassium stress in S. spontaneum is crucial for breeding sugarcane cultivars with efficient potassium utilization. Calcineurin B-like (CBL) protein is a calcium sensor that interacts with specific CBL-interacting protein kinases (CIPKs) upon plants' exposure to various abiotic stresses. RESULTS: In this study, nine CBL genes were identified from S. spontaneum. Phylogenetic analysis of 113 CBLs from 13 representative plants showed gene expansion and strong purifying selection in the CBL family. Analysis of CBL expression patterns revealed that SsCBL01 was the most commonly expressed gene in various tissues at different developmental stages. Expression analysis of SsCBLs under low K+ stress indicated that potassium deficiency moderately altered the transcription of SsCBLs. Subcellular localization showed that SsCBL01 is a plasma membrane protein and heterologous expression in yeast suggested that, while SsCBL01 alone could not absorb K+, it positively regulated K+ absorption mediated by the potassium transporter SsHAK1. CONCLUSIONS: This study provided insights into the evolution of the CBL gene family and preliminarily demonstrated that the plasma membrane protein SsCBL01 was involved in the response to low K+ stress in S. spontaneum.

Genome-wide systematic characterization of the HAK/KUP/KT gene family and its expression profile during plant growth and in response to low-K+ stress in Saccharum.

BACKGROUND: Plant genomes contain a large number of HAK/KUP/KT transporters, which play important roles in potassium uptake and translocation, osmotic potential regulation, salt tolerance, root morphogenesis and plant development. Potassium deficiency in the soil of a sugarcane planting area is serious. However, the HAK/KUP/KT gene family remains to be characterized in sugarcane (Saccharum). RESULTS: In this study, 30 HAK/KUP/KT genes were identified in Saccharum spontaneum. Phylogenetics, duplication events, gene structures and expression patterns were analyzed. Phylogenetic analysis of the HAK/KUP/KT genes from 15 representative plants showed that this gene family is divided into four groups (clades I-IV). Both ancient whole-genome duplication (WGD) and recent gene duplication contributed to the expansion of the HAK/KUP/KT gene family. Nonsynonymous to synonymous substitution ratio (Ka/Ks) analysis showed that purifying selection was the main force driving the evolution of HAK/KUP/KT genes. The divergence time of the HAK/KUP/KT gene family was estimated to range from 134.8 to 233.7 Mya based on Ks analysis, suggesting that it is an ancient gene family in plants. Gene structure analysis showed that the HAK/KUP/KT genes were accompanied by intron gain/loss in the process of evolution. RNA-seq data analysis demonstrated that the HAK/KUP/KT genes from clades II and III were mainly constitutively expressed in various tissues, while most genes from clades I and IV had no or very low expression in the tested tissues at different developmental stages. The expression of SsHAK1 and SsHAK21 was upregulated in response to low-K+ stress. Yeast functional complementation analysis revealed that SsHAK1 and SsHAK21 could rescue K+ uptake in a yeast mutant. CONCLUSIONS: This study provided insights into the evolutionary history of HAK/KUP/KT genes. HAK7/9/18 were mainly expressed in the upper photosynthetic zone and mature zone of the stem. HAK7/9/18/25 were regulated by sunlight. SsHAK1 and SsHAK21 played important roles in mediating potassium acquisition under limited K+ supply. Our results provide valuable information and key candidate genes for further studies on the function of HAK/KUP/KT genes in Saccharum.

Plasma microRNA detection standardization test.

BACKGROUND: MicroRNAs (miRNAs) can be used for early diagnosis of myocardial infarction. However, due to a lack of standardized operating procedures, their value for clinical application is low. METHODS: Detection of plasma miRNAs was optimized by analyzing factors influencing miRNA variance and myocardial infarction risk scores during analysis (extraction, reverse transcription, and real-time PCR) and pre-analysis (dietary status, anticoagulants, storage conditions, and hemolysis). RESULTS: Regarding variable factors during analysis, the centrifugal column method was superior to Trizol LS reagent when extracting miRNA from plasma. Recovery rate was highest with plasma volumes of 200 and 300 µL. During analysis, the main source of miRNA detection inaccuracy was derived from RNA extraction (mainly organic extraction), and not reverse transcription or PCR. MiRNA variance could be reduced by use of an internal reference. During analysis, 95% of risk score variation fluctuated within a range of 6.267. The variable factors pre-analysis mainly involved dietary status, anticoagulant selection, and storage conditions. Hemolysis positively correlated with miRNA levels, but there was no significant change in risk score after internal reference calibration. CONCLUSION: Preliminary standardization for miRNA detection provides a reference for clinical blood testing of miRNAs.

Improving the blast resistance of the elite rice variety Kongyu-131 by updating the pi21 locus.

BACKGROUND: As an elite japonica rice variety, Kongyu-131 has been cultivated for over 20 years in the third accumulated temperature zone of Heilongjiang Province, China. However, the cultivated area of Kongyu-131 has decreased each year due to extensive outbreaks of rice blast. To achieve the goals of improving blast resistance and preserving other desirable traits in Kongyu-131, a genome-updating method similar to repairing a bug in a computer program was adopted in this study. A new allele of the broad-spectrum blast resistance gene pi21 in the upland rice variety GKGH was mined by genetic analysis and introgressed into the genome of Kongyu-131 to upgrade its blast resistance. RESULT: QTL analysis was performed with an F2 population derived from a cross between Kongyu-131 and GKGH, and a blast resistance QTL was detected near the pi21 locus. Parental Pi21 sequence alignment showed that the pi21 of the donor (GKGH) was a new allele. By 5 InDel or SNP markers designed based on the sequence within and around pi21, the introgressed chromosome segment was shortened to less than 634 kb to minimize linkage drag by screening recombinants in the target region. The RRPG was 99.92%, calculated according to 201 SNP markers evenly distributed on 12 chromosomes. Artificial inoculation at the seedling stage showed that the blast resistance of the new Kongyu-131 was improved significantly. Field experiments also indicated that the improved Kongyu-131 had enhanced field resistance to rice blast and grain-quality traits similar to those of the original Kongyu-131. CONCLUSIONS: It is feasible to improve resistance to rice blast and preserve other desirable traits by precisely improving the Pi21 locus of Kongyu-131. Linkage drag can be eliminated effectively via recombinant selection on both sides of the target gene.

Limited potential of harvest index improvement to reduce methane emissions from rice paddies.

Rice is a staple food for nearly half of the world's population, but rice paddies constitute a major source of anthropogenic CH4 emissions. Root exudates from growing rice plants are an important substrate for methane-producing microorganisms. Therefore, breeding efforts optimizing rice plant photosynthate allocation to grains, i.e., increasing harvest index (HI), are widely expected to reduce CH4 emissions with higher yield. Here we show, by combining a series of experiments, meta-analyses and an expert survey, that the potential of CH4 mitigation from rice paddies through HI improvement is in fact small. Whereas HI improvement reduced CH4 emissions under continuously flooded (CF) irrigation, it did not affect CH4 emissions in systems with intermittent irrigation (II). We estimate that future plant breeding efforts aimed at HI improvement to the theoretical maximum value will reduce CH4 emissions in CF systems by 4.4%. However, CF systems currently make up only a small fraction of the total rice growing area (i.e., 27% of the Chinese rice paddy area). Thus, to achieve substantial CH4 mitigation from rice agriculture, alternative plant breeding strategies may be needed, along with alternative management.

Setd2 regulates quiescence and differentiation of adult hematopoietic stem cells by restricting RNA polymerase II elongation.

SET domain containing 2 (Setd2), encoding a histone methyltransferase, is associated with many hematopoietic diseases when mutated. By generating a novel exon 6 conditional knockout mouse model, we describe an essential role of Setd2 in maintaining the adult hematopoietic stem cells. Loss of Setd2 results in leukopenia, anemia, and increased platelets accompanied by hypocellularity, erythroid dysplasia, and mild fibrosis in bone marrow. Setd2 knockout mice show significantly decreased hematopoietic stem and progenitor cells except for erythroid progenitors. Setd2 knockout hematopoietic stem cells fail to establish long-term bone marrow reconstitution after transplantation because of the loss of quiescence, increased apoptosis, and reduced multiple-lineage terminal differentiation potential. Bioinformatic analysis revealed that the hematopoietic stem cells exit from quiescence and commit to differentiation, which lead to hematopoietic stem cell exhaustion. Mechanistically, we attribute an important Setd2 function in murine adult hematopoietic stem cells to the inhibition of the Nsd1/2/3 transcriptional complex, which recruits super elongation complex and controls RNA polymerase II elongation on a subset of target genes, including Myc Our results reveal a critical role of Setd2 in regulating quiescence and differentiation of hematopoietic stem cells through restricting the NSDs/SEC mediated RNA polymerase II elongation.

Culture-Dependent and -Independent Methods to Investigate the Predominant Microorganisms Associated with Wet Processed Coffee.

The fermentation process of Yunnan arabica coffee is a typical wet fermentation. Its excellent quality is closely related to microbes in the process of fermentation. The purpose of this study was to isolate and identify the microorganisms in the wet method of coffee processing in Yunnan Province, China. Microbial community structure and dominant bacterial species were evaluated by traditional cultivated separation method and PCR-DGGE technology, and were further analyzed in combination with the changes of organic acid content, activity of pectinase, and physical parameters (pH and temperature). A large number of microorganisms which can produce pectinase were found. Among them, Enterobacter cowanii, Pantoea agglomerans, Enterobacteriaceae bacterium, and Rahnella aquatilis were the predominant gram-negative bacteria, Bacillus cereus was the predominant gram-positive bacterium, Pichia kluyveri, Hanseniaspora uvarum, and Pichia fermentans were the predominant yeasts, and all those are pectinase-producing microorganisms. As for the contents of organic acids, oxalic was the highest, followed by acetic and lactic acids. Butyrate and propionate, which were unfavorable during the fermentation period, were barely discovered.

Sphingomonas qilianensis sp. nov., Isolated from Surface Soil in the Permafrost Region of Qilian Mountains, China.

A Gram-stain-negative, strictly aerobic, non-motile and rod-shaped bacterial strain, designated X1(T), was isolated from the permafrost region of Qilian Mountains in northwest of China. Phylogenetic analyses of 16S rRNA gene sequence revealed that strain X1(T) was a member of the genus Sphingomonas and shared the highest 16S rRNA gene sequence similarity with Sphingomonas oligophenolica JCM 12082(T) (96.9%), followed by Sphingomonas glacialis CGMCC 1.8957(T) (96.7%) and Sphingomonas alpina DSM 22537(T) (96.4%). Strain X1(T) was able to grow at 15-30 °C, pH 6.0-10.0 and with 0-0.3% NaCl (w/v). The DNA G+C content of the isolate was 64.8 mol%. Strain X1(T)-contained Q-10 as the dominant ubiquinone and C(18:1)ω7c, C(16:1)ω7c, C(16:0) and C(14:0) 2-OH as the dominant fatty acids. The polar lipid profile of strain XI(T)-contained sphingoglycolipid, phosphatidylglycerol, phosphatidylethanolamine, one unidentified glycolipid and two unidentified phospholipid. Due to the phenotypic and genetic distinctiveness and other characteristic studied in this article, we consider X1(T) as a novel species of the genus Sphingomonas and propose to name it Sphingomonas qilianensis sp. nov. The type strain is X1(T) (=CGMCC 1.15349(T) = KCTC 42862(T)).

Flavobacterium buctense sp. nov., isolated from freshwater.

A gram-negative, non-gliding motile, aerobic bacterium, designated as strain T7(T), was isolated from freshwater of Chishui River flowing through Maotai town, Guizhou Province, southwest of China. Based on the 16S rRNA gene sequence analysis, the isolate was identified as a member of the genus Flavobacterium and that shared less than 97 % sequence similarities with recognized Flavobacterium species. Its closest phylogenetic relative was Flavobacterium dankookense (96.9 %), followed by Flavobacterium cheonhonense (96.8 %) and Flavobacterium macrobrachii (96.7 %). The strain formed smooth yellow colonies on R2A plates, and cells were observed to be short rods. Strain T7(T) was found to be able to grow at 15-30 °C (optimum 25 °C), at NaCl concentration of 0-0.5 % (optimum 0 %) and at pH 6.5-9.5 (optimum pH 7.5). Catalase and oxidase tests were positive. Polar lipids of strain T7(T) included phosphatidylethanolamine, four unidentified polar lipids, one unidentified phospholipid and one unidentified aminolipid. Chemotaxonomic analysis revealed menaquinone-6 as the dominant respiratory quinone and C(15:0), iso-C(15:0) and iso-C(15:1) as the major fatty acids. The DNA G+C content of strain T7(T) was determined to be 38.2 mol%. On the basis of phylogenetic, phenotypic and genetic data obtained in this study, strain T7(T) represents a novel species of the genus Flavobacterium, for which the name Flavobacterium buctense sp. nov. is proposed. The type strain is T7(T) (=JCM 30750=CGMCC 1.15216).

Polymorphobacter fuscus sp. nov., isolated from permafrost soil, and emended description of the genus Polymorphobacter.

Strain D40PT, representing a novel Gram-stain-negative, obligately aerobic, bacteriochlorophyll a-containing bacterium of the α-4 subgroup of the phylum Proteobacteria, was isolated from permafrost soil of Kunlun mountains gap, Qinghai-Tibet plateau. Cells were non-motile rod-cocci and formed brown-pigmented colonies. According to the absorption spectrum, carotenoids and two different photosynthetic light-harvesting complexes, an LHI complex and a B800-835-type peripheral LHII complex, were present in the cells. The strain was oxidase-negative and catalase-positive. The predominant fatty acids of strain D40PT were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C17 : 1ω6c and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The main polar lipids were phosphatidylethanolamine, phosphatidylglycerol, unidentified phospholipid, two glycolipids and sphingoglycolipid. The major respiratory quinone was ubiquinone-10, whereas ubiquinone-9 was present in smaller amounts. The 16S rRNA gene sequence similarity to the closest phylogenetic relative, Polymorphobacter multimanifer JCM 18140T, was 97.5 %. DNA-DNA relatedness (ΔTm) between strain D40PT and P. multimanifer was 12.4 °C. The G+C content of the genomic DNA of strain D40PT was 67.4 mol%. Accordingly, the strain represents a novel species, for which the name Polymorphobacter fuscus sp. nov. is proposed. The type strain is D40PT ( = CGMCC 1.12714T = JCM 19740T). An emended description of the genus Polymorphobacter is also proposed.

Qipengyuania sediminis gen. nov., sp. nov., a member of the family Erythrobacteraceae isolated from subterrestrial sediment.

A Gram-reaction-negative, non-motile, facultatively aerobic bacterium, designated strain M1T, was isolated from a subterrestrial sediment sample of Qiangtang Basin in Qinghai-Tibetan plateau, China. The strain formed rough yellow colonies on R2A plates. Cells were oval or short rod-shaped, catalase-positive and oxidase-negative. Phylogenetic analyses based on 16S rRNA gene sequences indicated that the isolate belonged to the family Erythrobacteraceae and showed 96.2­96.4 % 16S rRNA gene sequence similarities to its closest relatives. Chemotaxonomic analysis revealed ubiquinone-10 (Q10) as the dominant respiratory quinone of strain M1T and C17 : 1ω6c (44.2 %) and C18 : 1ω7c (13.7 %) as the major fatty acids. The major polar lipids were phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, sphingoglycolipid, three unidentified glycolipids, one unidentified phosphoglycolipid and one unidentified lipid. The DNA G+C content of strain M1T was 73.7 mol%. On the basis of phenotypic, phylogenetic and genotypic data presented in this study, strain M1T represents a novel species of a new genus in the family Erythrobacteraceae, for which the name Qipengyuania sediminis gen. nov., sp. nov. is proposed. The type strain of the type species is M1T ( = CGMCC 1.12928T = JCM 30182T).

Sphingomonas arantia sp. nov., isolated from Hoh Xil basin, China.

A Gram-negative, rod-shaped, non-motile, non-spore forming, aerobic, orange-pigmented bacterium, designated strain 6P(T), was isolated from a soil sample collected from the Hoh Xil basin, China. Strain 6P(T) grew optimally at 25 °C, pH 7.0-7.5 and NaCl concentration of 0-1 % (w/v). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 6P(T) belongs to the genus Sphingomonas, with high sequence similarity (97.1 %) to Sphingomonas fennica. The DNA-DNA hybridization homology with S. fennica DSM 13665(T) was 45.3 %. The DNA G+C content of the novel strain is 65.3 mol%. The isolate contained Q-10 as the only respiratory quinone. The major polar lipids are diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC) and sphingoglycolipid (SGL). C18:1 ω7c and C16:1 ω7c are the major fatty acids. On the basis of the polyphasic evidence presented, strain 6P(T) represents a novel species of the genus Sphingomonas, for which the name Sphingomonas arantia sp. nov. is proposed. The type strain is 6P(T) (=CGMCC 1.12702(T) = JCM 19855(T)).

Transcription Factor STAT3-Activated LDHB Promotes Tumor Properties of Endometrial Cancer Cells by Inducing MDH2 Expression.

The pathogenesis of endometrial cancer (EC) involves the regulation of lactate dehydrogenases. However, the role and mechanism of lactate dehydrogenase-B (LDHB) in EC progression have not been studied. The mRNA levels of LDHB and malate dehydrogenase 2 (MDH2) were detected by quantitative real-time polymerase chain reaction. Protein expression was checked by western blotting and immunohistochemistry assays. Cell proliferation, apoptosis, and invasion were analyzed by 5-Ethynyl-2'-deoxyuridine, transwell, and flow cytometry assay, respectively. Glycolysis was investigated using Glucose Assay Kit, CheKine™ Micro Lactate Assay Kit, and ADP/ATP ratio assay kit. An in vivo tumor formation assay was conducted to disclose the effect of LDHB on tumor growth in vivo. The associations among signal transducer and activator of transcription 3 (STAT3), LDHB, and MDH2 were predicted through JASPAR or GeneMANIA online database and identified by chromatin immunoprecipitation assay, dual-luciferase reporter assay, and co-immunoprecipitation assay. LDHB expression was increased in EC tissues and cells in comparison with normal endometrial tissues and human endometrial stromal cells. LDHB had the potential as a biomarker to predict the prognosis of EC patients. In addition, LDHB knockdown inhibited the proliferation, invasion, and glycolysis and promoted apoptosis of RL95-2 and Ishikawa cells. LDHB knockdown inhibited tumor property of Ishikawa cells in vivo. STAT3 bound to the promoter region of LDHB, and STAT3 silencing-induced effects were relieved after LDHB upregulation. LDHB interacted with and regulated MDH2 expression. Moreover, MDH2 overexpression rescued LDHB knockdown-induced effects on EC cell phenotypes. STAT3-activated LDHB promoted endometrial cancer cell malignancy by inducing MDH2 production.

Ectopic expression of the transcription factor ONECUT3 drives a complex karyotype in myelodysplastic syndromes.

Chromosomal instability is a prominent biological feature of myelodysplastic syndromes (MDS), with over 50% of patients with MDS harboring chromosomal abnormalities or a complex karyotype (CK). Despite this observation, the mechanisms underlying mitotic and chromosomal defects in MDS remain elusive. In this study, we identified ectopic expression of the transcription factor ONECUT3, which is associated with CKs and poorer survival outcomes in MDS. ONECUT3-overexpressing cell models exhibited enrichment of several notable pathways, including signatures of sister chromosome exchange separation and mitotic nuclear division with the upregulation of INCENP and CDCA8 genes. Notably, dysregulation of chromosome passenger complex (CPC) accumulation, besides the cell equator and midbody, during mitotic phases consequently caused cytokinesis failure and defective chromosome segregation. Mechanistically, the homeobox (HOX) domain of ONECUT3, serving as the DNA binding domain, occupied the unique genomic regions of INCENP and CDCA8 and transcriptionally activated these 2 genes. We identified a lead compound, C5484617, that functionally targeted the HOX domain of ONECUT3, inhibiting its transcriptional activity on downstream genes, and synergistically resensitized MDS cells to hypomethylating agents. This study revealed that ONECUT3 promoted chromosomal instability by transcriptional activation of INCENP and CDCA8, suggesting potential prognostic and therapeutic roles for targeting high-risk MDS patients with a CK.

General combining ability of most yield-related traits had a genetic basis different from their corresponding traits per se in a set of maize introgression lines.

Evaluation of combining ability is a crucial process in hybrid breeding, and dissection of the genetic basis of combining ability will facilitate hybrid breeding. In this study, molecular markers significantly associated with general combining ability (GCA) of seven yield-related traits and the traits per se were detected in a set of maize introgression lines (ILs) under three environments. Totally 25 and 31 significant loci for GCA and the traits per se were commonly detected under multiple environments, respectively. Correlation analysis and comparison among these significant loci revealed that the genetic basis of GCA of these yield-related traits was generally different from that of the traits per se except for the trait of ear row number. In addition, GCA of the ILs was positively and significantly correlated to the total relative effects of significant GCA loci in the ILs in general, implying that the GCA loci identified in this study would be useful in molecular breeding. Correlation analysis also showed that the GCA of yield per plant was strongly correlated to the GCA of kernel number per row, ear length and 100-kernel-weight, thus these traits were more important in genetic improvement for GCA. Results in this study would provide useful information for hybrid breeding in maize.

Relationship between cancer-related fatigue and personality in patients with breast cancer after chemotherapy.

BACKGROUND: This study aimed to explore the relationship between cancer-related fatigue (CRF) and personality in patients with breast cancer after chemotherapy. METHODS: A cross-sectional study was conducted to study the relationship between CRF and personality in breast cancer patients after chemotherapy. CRF and personality were measured by the cancer fatigue score and the Eysenck Personality Questionnaire, respectively. RESULTS: A total of 300 breast cancer patients who had received chemotherapy were recruited to this study. Eysenck Personality Questionnaire scores of psychoticism, introversion, and extroversion in the patients were lower than the norm level (p < 0.01), but those of neuroticism and lie were higher than the norm level (p < 0.01). Multivariate analyses showed positive correlation between psychoticism and affective fatigue, neuroticism and total fatigue, and physical fatigue and cognitive fatigue. Multivariate analyses also showed negative correlation between introversion or extroversion and total fatigue, physical fatigue or affective fatigue, and lie and total fatigue or cognitive fatigue. CONCLUSIONS: There was CRF in patients with breast cancer after chemotherapy. Psychoticism, extroversion/introversion, neuroticism, and lie are correlated with CRF in breast cancer patients after chemotherapy.