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Key message: QTLs for growth habit are identified on Arahy.15 and Arahy.06 in peanut, and diagnostic markers are developed and validated for further use in marker-assisted breeding. Peanut is a unique legume crop because its pods develop and mature underground. The pegs derive from flowers following pollination, then reach the ground and develop into pods in the soil. Pod number per plant is influenced by peanut growth habit (GH) that has been categorized into four types, including erect, bunch, spreading and prostrate. Restricting pod development at the plant base, as would be the case for peanut plants with upright lateral branches, would decrease pod yield. On the other hand, GH characterized by spreading lateral branches on the ground would facilitate pod formation on the nodes, thereby increasing yield potential. We describe herein an investigation into the GH traits of 521 peanut recombinant inbred lines grown in three distinct environments. Quantitative trait loci (QTLs) for GH were identified on linkage group (LG) 15 between 203.1 and 204.2 cM and on LG 16 from 139.1 to 139.3 cM. Analysis of resequencing data in the identified QTL regions revealed that single nucleotide polymorphism (SNP) or insertion and/or deletion (INDEL) at Arahy15.156854742, Arahy15.156931574, Arahy15.156976352 and Arahy06.111973258 may affect the functions of their respective candidate genes, Arahy.QV02Z8, Arahy.509QUQ, Arahy.ATH5WE and Arahy.SC7TJM. These SNPs and INDELs in relation to peanut GH were further developed for KASP genotyping and tested on a panel of 77 peanut accessions with distinct GH features. This study validates four diagnostic markers that may be used to distinguish erect/bunch peanuts from spreading/prostrate peanuts, thereby facilitating marker-assisted selection for GH traits in peanut breeding. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nasal filter obtained the actual inhaled PM 10 for urban individual women. • Air filter-based sampling underestimated the inhaled dose and health risk of PM 10. • Women closer to traffic emissions inhaled the most PM 10 and heavy metals. • Women exposed outdoors faced greater non-cancer and cancer risks. • Women who work outdoors are more likely to develop asthma during haze event. Urban populations, especially women, are vunerable to exposure to airborne pollution, particularly inhalable particulates (PM 10). Thus, more accurate measurement of PM 10 levels and evaluating their health effects is critical for guiding policy to improve human health. Previous studies obtained personal PM 10 with time-weighted average by air filter-based sampling (AFS), which ignores individual differences and behavioral patterns. Here, we used nasal filters instead of AFS to obtain actual inhaled PM 10 under short-term exposure for urban dwelling women during a severe haze event in Beijing in 2016. The levels of six heavy metals such as As, Cd, Ni, Cr, Pb, and Co in PM 10 were investigated, and carcinogenic and non-carcinogenic risks evaluated based on an adjusted US EPA health risk assessment model. The health endpoints for urban dwelling women were further assessed through an exposure-reponse model. We found that the hourly inhaled dose of PM 10 obtained through the nasal filter was about 2.5–17.6 times that obtained by AFS, which also resulted in 4.41–11.30 times more morbidity than estimated by AFS (p < 0.05). Proximity to traffic emissions resulted in greater exposure to particulate matter (>18.8 μg/kg·h) and heavy metals (>2.2 ng/kg·h), and these populations are therefore at greatest risk of developing non-cancer (HI = 4.16) and cancer (R t = 7.8 × 10−3) related morbities. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) viremia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The purpose of this study was to evaluate the impacts of early-onset EBV viremia in acute leukemia (AL) patients who underwent allo-HSCT with anti-thymocyte globulin (ATG)-containing myeloablative conditioning (MAC) regimen. Two hundred and ninety-six patients were included between January 2013 and December 2015. In 126 patients (42.6%) who developed early-onset EBV viremia, with a median time of 48 (range 18~99) days after allo-HSCT. The cumulative incidence of EBV viremia at 30 and 90 days after allo-HSCT were 4.1 and 39.9%, respectively. Prognostic analysis showed that the adjusted overall survival in early-EBVpos group was significantly lower than early-EBVneg group within the first 26.7 months after allo-HSCT [hazard ratio (HR), 1.63, P = 0.012], but significantly higher than those afterward (after 26.7 months: HR 0.11, P = 0.035); for the adjusted event-free survival, early-EBVpos group was significantly inferior in early-EBVpos group within the first 10.8 months after transplantation (HR: 1.55, P = 0.042), and this adverse effect was not detected any more after 10.8 months (HR: 0.58, P = 0.107). Compared with early-EBVneg group after adjusting by aGVHD and CMV viremia, HR for death from transplant-related mortality was 2.78-fold higher in patients with early-EBV viremia in piecewise constant Cox analysis (P = 0.006), and this adverse effect was not detected any more after the cut-point time (HR: 0.67, P = 0.361). No differences in terms of relapse and relapse mortality were observed between early-EBVpos and early-EBVneg group (P > 0.05). In conclusion, the impacts on transplant outcomes of early-EBV viremia were time-dependent, which may help to optimize management strategies for early-EBV viremia after allo-HSCT, especially in AL patients with ATG-containing MAC regimen. [ABSTRACT FROM AUTHOR]

The long-term trend and seasonal variability of sea surface temperature (SST) over tropical Indo-Pacific region under the global warming projection simulated by FIO-ESM model are analyzed. At seasonal time scale, significant warming trend over Indo-Pacific area is well captured by FIO-ESM model over the warm pool region under RCP8.5 scenario. The La Niña-like warming pattern is dominant in the tropical Pacific and the negative Indian Ocean Dipole warming pattern takes place in the Indian Ocean in global warming projection separately. The strength of SST warming trend is found to be seasonal dependent over Indo-Pacific region. The spatial distribution of calendar month where fastest/slowest SST warming trend take place in tropical Indo-Pacific has been assessed in FIO-ESM simulation, which is corresponded with the distribution of SST climatology closely in Pacific but not in Indian Ocean. [ABSTRACT FROM AUTHOR]

Aims. Using both data mining and network pharmacology methods, this paper aims to construct a molecule-target-disease network for medicines used for treating mastitis, mine out targets, and signaling pathways related to mastitis and explore the mechanism of Chinese materia medica (CMM) prescriptions in treating mastitis. Methods. A total of 131 CMM prescriptions for treating mastitis were collected from clinical practice and related literatures. A database of prescriptions for treating mastitis (DPTM) was then constructed. Based on data mining method, Traditional Chinese Medicine Inheritance Support System (TCMISS) was employed to mine out high-frequency CMM and key CMM combinations in DPTM. Subsequently, TCM Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Information Database (TCM-ID) were searched for the targets of ingredients of high-frequency CMM. Then, Bioinformatics Analysis Tool for Molecular Mechanism of TCM (BATMAN-TCM) was searched for diseases and signaling pathways corresponding to the targets of key CMM combinations. The obtained results were denoted as results 1. In addition, human disease database MalaCards was searched for targets and signaling pathways related to mastitis. The obtained results were denoted as results 2. Results 1 and 2 were compared to obtain targets and signaling pathways included in both results, namely, mastitis-related targets of TCMs and mastitis-related signaling pathways that CMM involves in. Then, the biological functions of these targets and signaling pathways were investigated, on which basis the mechanism of CMM prescriptions in treating mastitis was explored. Results. A total of 12 key TCM combinations were identified. Taraxaci Herba, Glycyrrhizae Radix et Rhizoma, Paeoniae Radix Alba, semen citri reticulatae, etc. were CMM with the highest frequency of use for treating mastitis. The potential targets of these high-frequency CMM in treating mastitis were intercellular adhesion molecule 1 (ICAM-1), interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP), and lactotransferrin. The potential signaling pathways that key CMM combinations may involve in during mastitis treatment were NF-κB signaling pathway, immune system, PI3K/Akt signaling pathway, and TNF signaling pathway. Conclusions. From a perspective of network pharmacology, molecule-target-disease analysis may serve as an entry point for the research of mechanism of CMM. On this basis, we studied the mechanism of CMM prescriptions in treating mastitis by data mining and comparison of results. Our work thus provides a new idea and method for studying the working mechanism of CMM prescriptions. [ABSTRACT FROM AUTHOR]

For peanut, the lack of stable cytological markers is a barrier to tracking specific chromosomes, elucidating the genetic relationships between genomes and identifying chromosomal variations. Chromosome mapping using single-copy oligonucleotide (oligo) probe libraries has unique advantages for identifying homologous chromosomes and chromosomal rearrangements. In this study, we developed two whole-chromosome single-copy oligo probe libraries, LS-7A and LS-8A, based on the reference genome sequences of chromosomes 7A and 8A of Arachis duranensis. Fluorescence in situ hybridization (FISH) analysis confirmed that the libraries could specifically paint chromosomes 7 and 8. In addition, sequential FISH and electronic localization of LS-7A and LS-8A in A. duranensis (AA) and A. ipaensis (BB) showed that chromosomes 7A and 8A contained translocations and inversions relative to chromosomes 7B and 8B. Analysis of the chromosomes of wild Arachis species using LS-8A confirmed that this library could accurately and effectively identify A genome species. Finally, LS-7A and LS-8A were used to paint the chromosomes of interspecific hybrids and their progenies, which verified the authenticity of the interspecific hybrids and identified a disomic addition line. This study provides a model for developing specific oligo probes to identify the structural variations of other chromosomes in Arachis and demonstrates the practical utility of LS-7A and LS-8A. [ABSTRACT FROM AUTHOR]

The main cause of second-generation antipsychotic (SGA)-induced obesity is considered due to the antagonism of serotonin 2c receptors (5-HT2cR) and activation of ghrelin receptor type 1a (GHSR1a) signalling. It is reported that 5-HT2cR interacted with GHSR1a, however it is unknown whether one of the SGA olanzapine alters the 5-HT2cR/GHSR1a interaction, affecting orexigenic neuropeptide signalling in the hypothalamus. We found that olanzapine treatment increased average energy intake and body weight gain in mice; olanzapine treatment also increased orexigenic neuropeptide (NPY) and GHSR1a signaling molecules, pAMPK, UCP2, FOXO1 and pCREB levels in the hypothalamus. By using confocal fluorescence resonance energy transfer (FRET) technology, we found that 5-HT2cR interacted/dimerised with the GHSR1a in the hypothalamic neurons. As 5-HT2cR antagonist, both olanzapine and S242084 decreased the interaction between 5-HT2cR and GHSR1a and activated GHSR1a signaling. The 5-HT2cR agonist lorcaserin counteracted olanzapine-induced attenuation of interaction between 5-HT2cR and GHSR1a and inhibited activation of GHSR1a signalling and NPY production. These findings suggest that 5-HT2cR antagonistic effect of olanzapine in inhibition of the interaction of 5-HT2cR and GHSR1a, activation GHSR1a downstream signaling and increasing hypothalamic NPY, which may be the important neuronal molecular mechanism underlying olanzapine-induced obesity and target for prevention metabolic side effects of antipsychotic management in psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background: This study aims to decipher the genetic basis governing yield components and quality attributes of peanuts, a critical aspect for advancing molecular breeding techniques. Integrating genotype re-sequencing and phenotypic evaluations of seven yield components and two grain quality traits across four distinct environments allowed for the execution of a genome-wide association study (GWAS). Results: The nine phenotypic traits were all continuous and followed a normal distribution. The broad heritability ranged from 88.09 to 98.08%, and the genotype-environment interaction effects were all significant. There was a highly significant negative correlation between protein content (PC) and oil content (OC). The 10× genome re-sequencing of 199 peanut accessions yielded a total of 631,988 high-quality single nucleotide polymorphisms (SNPs), with 374 significant SNP loci identified in association with the nine traits of interest. Notably, 66 of these pertinent SNPs were detected in multiple environments, and 48 of them were linked to multiple traits of interest. Five loci situated on chromosome 16 (Chr16) exhibited pleiotropic effects on yield traits, accounting for 17.64–32.61% of the observed phenotypic variation. Two loci on Chr08 were found to be strongly associated with protein and oil contents, accounting for 12.86% and 14.06% of their respective phenotypic variations, respectively. Linkage disequilibrium (LD) block analysis of these seven loci unraveled five nonsynonymous variants, leading to the identification of one yield-related candidate gene and two quality-related candidate genes. The correlation between phenotypic variation and SNP loci in these candidate genes was validated by Kompetitive allele-specific PCR (KASP) marker analysis. Conclusions: Overall, molecular markers were developed for genetic loci associated with yield and quality traits through a GWAS investigation of 199 peanut accessions across four distinct environments. These molecular tools can aid in the development of desirable peanut germplasm with an equilibrium of yield and quality through marker-assisted breeding. [ABSTRACT FROM AUTHOR]

Background: Bacterial wilt caused by Ralstonia solanacearum severely affects peanut (Arachis hypogaea L.) yields. The breeding of resistant cultivars is an efficient means of controlling plant diseases. Therefore, identification of resistance genes effective against bacterial wilt is a matter of urgency. The lack of a reference genome for a resistant genotype severely hinders the process of identification of resistance genes in peanut. In addition, limited information is available on disease resistance-related pathways in peanut. Results: Full-length transcriptome data were used to generate wilt-resistant and -susceptible transcript pools. In total, 253,869 transcripts were retained to form a reference transcriptome for RNA-sequencing data analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of differentially expressed genes revealed the plant-pathogen interaction pathway to be the main resistance-related pathway for peanut to prevent bacterial invasion and calcium plays an important role in this pathway. Glutathione metabolism was enriched in wilt-susceptible genotypes, which would promote glutathione synthesis in the early stages of pathogen invasion. Based on our previous quantitative trait locus (QTL) mapping results, the genes arahy.V6I7WA and arahy.MXY2PU, which encode nucleotide-binding site-leucine-rich repeat receptor proteins, were indicated to be associated with resistance to bacterial wilt. Conclusions: This study identified several pathways associated with resistance to bacterial wilt and identified candidate genes for bacterial wilt resistance in a major QTL region. These findings lay a foundation for investigation of the mechanism of resistance to bacterial wilt in peanut. [ABSTRACT FROM AUTHOR]

Phenylalanine ammonia-lyase (PAL) is an essential enzyme in the phenylpropanoid pathway, in which numerous aromatic intermediate metabolites play significant roles in plant growth, adaptation, and disease resistance. Cultivated peanuts are highly susceptible to Aspergillus flavus L. infection. Although PAL genes have been characterized in various major crops, no systematic studies have been conducted in cultivated peanuts, especially in response to A. flavus infection. In the present study, a systematic genome-wide analysis was conducted to identify PAL genes in the Arachis hypogaea L. genome. Ten AhPAL genes were distributed unevenly on nine A. hypogaea chromosomes. Based on phylogenetic analysis, the AhPAL proteins were classified into three groups. Structural and conserved motif analysis of PAL genes in A. hypogaea revealed that all peanut PAL genes contained one intron and ten motifs in the conserved domains. Furthermore, synteny analysis indicated that the ten AhPAL genes could be categorized into five pairs and that each AhPAL gene had a homologous gene in the wild-type peanut. Cis-element analysis revealed that the promoter region of the AhPAL gene family was rich in stress- and hormone-related elements. Expression analysis indicated that genes from Group I (AhPAL1 and AhPAL2), which had large number of ABRE, WUN, and ARE elements in the promoter, played a strong role in response to A. flavus stress. [ABSTRACT FROM AUTHOR]

The capability of embryogenic callus induction is a prerequisite for in vitro plant regeneration. However, embryogenic callus induction is strongly genotype-dependent, thus hindering the development of in vitro plant genetic engineering technology. In this study, to examine the genetic variation in embryogenic callus induction rate (CIR) in peanut (Arachis hypogaea L.) at the seventh, eighth, and ninth subcultures (T7, T8, and T9, respectively), we performed genome-wide association studies (GWAS) for CIR in a population of 353 peanut accessions. The coefficient of variation of CIR among the genotypes was high in the T7, T8, and T9 subcultures (33.06%, 34.18%, and 35.54%, respectively), and the average CIR ranged from 1.58 to 1.66. A total of 53 significant single-nucleotide polymorphisms (SNPs) were detected (based on the threshold value −log10(p) = 4.5). Among these SNPs, SNPB03-83801701 showed high phenotypic variance and neared a gene that encodes a peroxisomal ABC transporter 1. SNPA05-94095749, representing a nonsynonymous mutation, was located in the Arahy.MIX90M locus (encoding an auxin response factor 19 protein) at T8, which was associated with callus formation. These results provide guidance for future elucidation of the regulatory mechanism of embryogenic callus induction in peanut. [ABSTRACT FROM AUTHOR]

Background: Pod shell thickness (PST) is an important agronomic trait of peanut because it affects the ability of shells to resist pest infestations and pathogen attacks, while also influencing the peanut shelling process. However, very few studies have explored the genetic basis of PST. Results: An F2 segregating population derived from a cross between the thick-shelled cultivar Yueyou 18 (YY18) and the thin-shelled cultivar Weihua 8 (WH8) was used to identify the quantitative trait loci (QTLs) for PST. On the basis of a bulked segregant analysis sequencing (BSA-seq), four QTLs were preliminarily mapped to chromosomes 3, 8, 13, and 18. Using the genome resequencing data of YY18 and WH8, 22 kompetitive allele-specific PCR (KASP) markers were designed for the genotyping of the F2 population. Two major QTLs (qPSTA08 and qPSTA18) were identified and finely mapped, with qPSTA08 detected on chromosome 8 (0.69-Mb physical genomic region) and qPSTA18 detected on chromosome 18 (0.15-Mb physical genomic region). Moreover, qPSTA08 and qPSTA18 explained 31.1–32.3% and 16.7–16.8% of the phenotypic variation, respectively. Fifteen genes were detected in the two candidate regions, including three genes with nonsynonymous mutations in the exon region. Two molecular markers (Tif2_A08_31713024 and Tif2_A18_7198124) that were developed for the two major QTL regions effectively distinguished between thick-shelled and thin-shelled materials. Subsequently, the two markers were validated in four F2:3 lines selected. Conclusions: The QTLs identified and molecular markers developed in this study may lay the foundation for breeding cultivars with a shell thickness suitable for mechanized peanut shelling. [ABSTRACT FROM AUTHOR]

Background: Web blotch is one of the most important foliar diseases worldwide in peanut (Arachis hypogaea L.). The identification of quantitative trait loci (QTLs) for peanut web blotch resistance represents the basis for gene mining and the application of molecular breeding technologies. Results: In this study, a peanut recombinant inbred line (RIL) population was used to map QTLs for web blotch resistance based on high-throughput genome-wide sequencing. Frequency distributions of disease grade and disease index in five environments indicated wide phenotypic variations in response to web blotch among RILs. A high-density genetic map was constructed, containing 3634 bin markers distributed on 20 peanut linkage groups (LGs) with an average genetic distance of 0.5 cM. In total, eight QTLs were detected for peanut web blotch resistance in at least two environments, explaining from 2.8 to 15.1% of phenotypic variance. Two major QTLs qWBRA04 and qWBRA14 were detected in all five environments and were linked to 40 candidate genes encoding nucleotide-binding site leucine-rich repeat (NBS-LRR) or other proteins related to disease resistances. Conclusions: The results of this study provide a basis for breeding peanut cultivars with web blotch resistance. [ABSTRACT FROM AUTHOR]

Peanut (Arachis hypogaea L.) is an important oilseed crop worldwide. Improving its yield is crucial for sustainable peanut production to meet increasing food and industrial requirements. Deciphering the genetic control underlying peanut kernel weight and size, which are essential components of peanut yield, would facilitate high-yield breeding. A high-density single nucleotide polymorphism (SNP)-based linkage map was constructed using a recombinant inbred lines (RIL) population derived from a cross between the variety Yuanza9102 and a germplasm accession wt09-0023. Kernel weight and size quantitative trait loci (QTLs) were co-localized to a 0.16 Mb interval on Arahy07 using inclusive composite interval mapping (ICIM). Analysis of SNP, and Insertion or Deletion (INDEL) markers in the QTL interval revealed a gene encoding a pentatricopeptide repeat (PPR) superfamily protein as a candidate closely linked with kernel weight and size in cultivated peanut. Examination of the PPR gene family indicated a high degree of collinearity of PPR genes between A. hypogaea and its diploid progenitors, Arachis duranensis and Arachis ipaensis. The candidate PPR gene, Arahy.JX1V6X, displayed a constitutive expression pattern in developing seeds. These findings lay a foundation for further fine mapping of QTLs related to kernel weight and size, as well as validation of candidate genes in cultivated peanut. [ABSTRACT FROM AUTHOR]

Background: CD19-modified CAR-T cells greatly influence responses in patients with relapsed/refractory acute lymphoblastic leukemia (ALL). However, recurrence remains a challenge, and reinfusion of CAR-T cells is not always effective. Sequential infusion of humanized CD19-modified and CD22-modified CAR-T cells may overcome this issue and induce remission. Methods: We examined treatment with sequential infusion of humanized CD19-modified and CD22-modified CAR-T cells in a patient with relapsed ALL previously exposed to murine-derived anti-CD19 CAR-T cells. Results: At ~6 weeks after treatment, repeated bone marrow smear and flow cytometry analysis revealed no lymphoblasts. Conclusion: Our results suggest that sequential infusion of humanized CD19-modified and CD22-modified CAR-T cells is a valuable option for relapsed patients with prior infusion of murine-derived, CD19-directed CAR-T cells. [ABSTRACT FROM AUTHOR]

The El Niño event is an air-sea interaction phenomenon over the tropical Pacific region, which is classified by canonical El Niño, El Niño Modoki I, and El Niño Modoki II based on the distinct temporal and spatial distributions of sea surface temperature anomalies. This research reveals that different types of El Niño events present distinct effects on the variation of Wyrtki jets over the equatorial Indian Ocean in boreal autumn season. The autumn Wyrtki jets of the Indian Ocean are significantly weaken during the canonical El Niño event. While, during the El Niño Modoki I and II events, the Wyrtki jets are stronger than climatology. Further analysis illustrates the anomalous Walker Circulations associated with different types of El Niño events are responsible for the variation of Wyrtki jets via the modulation of sea surface wind forcing over the Indo-Pacific region. [ABSTRACT FROM AUTHOR]

Keywords: Peanut (Arachis hypogaea L.); CRISPR/Cas9; base-editing; ALS; herbicide-resistant EN Peanut (Arachis hypogaea L.) CRISPR/Cas9 base-editing ALS herbicide-resistant 1923 1925 3 09/20/23 20231001 NES 231001 Genome editing has been employed to introduce accurate and predictable genetic mutations in plants, gaining wide acceptance due to its high efficiency, precision, usability and significant potential for crop improvement (Manghwar I et al i ., [5]). The gained herbicide resistance appears to be gene dosage-dependent, whereby the T SB 2 sb plants with simultaneous base conversions in both I AhALS2-A i and I AhALS2-B i genes grew and thrived upon herbicide application, while those with mutations in only one I ALS i exhibited no newly grown leaves (Figure 1f). Creation of herbicide-resistance in allotetraploid peanut using CRISPR/Cas9-meditated cytosine base-editing. [Extracted from the article]

Background: Non-invasive detection of blood-based markers is a critical clinical need. Plasma has become the main sample type for clinical proteomics research because it is easy to obtain and contains measurable protein biomarkers that can reveal disease-related physiological and pathological changes. Many efforts have been made to improve the depth of its identification, while there is an increasing need to improve the throughput and reproducibility of plasma proteomics analysis in order to adapt to the clinical large-scale sample analysis. Methods: We have developed and optimized a robust plasma analysis workflow that combines an automated sample preparation platform with a micro-flow LC–MS-based detection method. The stability and reproducibility of the workflow were systematically evaluated and the workflow was applied to a proof-of-concept plasma proteome study of 30 colon cancer patients from three age groups. Results: This workflow can analyze dozens of samples simultaneously with high reproducibility. Without protein depletion and prefractionation, more than 300 protein groups can be identified in a single analysis with micro-flow LC–MS system on a Orbitrap Exploris 240 mass spectrometer, including quantification of 35 FDA approved disease markers. The quantitative precision of the entire workflow was acceptable with median CV of 9%. The preliminary proteomic analysis of colon cancer plasma from different age groups could be well separated with identification of potential colon cancer-related biomarkers. Conclusions: This workflow is suitable for the analysis of large-scale clinical plasma samples with its simple and time-saving operation, and the results demonstrate the feasibility of discovering significantly changed plasma proteins and distinguishing different patient groups. [ABSTRACT FROM AUTHOR]

Nitrogen, one of the essential elements, is a key determinant for improving peanut growth and yield. GATA zinc finger transcription factors have been found to be involved in regulation of nitrogen metabolism. However, a systematic characterization of the GATA gene family and patterns of their expression under different nitrogen levels remains elusive. In this study, a total of 45 GATA genes distributed among 17 chromosomes were identified in the peanut genome and classified into three subfamilies I, II and III with 26, 13 and 6 members, respectively, whose physicochemical characteristics, gene structures and conserved motifs were also analyzed. Furthermore, the optimal level of nitrogen fertilizer on the growth of peanut cultivar Yuhua 23 was determined by pod yield and value cost ratio from 2020 to 2022, and the results revealed that 150 kg hm−2 nitrogen was the best for cultivation of peanut Yuhua 23 because of its highest pod yield and relatively higher VCR of more than four. In addition, expression patterns of peanut GATA genes under different nitrogen levels were detected by real-time quantitative PCR and several GATA genes were significantly changed under a nitrogen level of 150 kg hm−2. Overall, the above results would be helpful for further understanding biological functions of the GATA gene family in cultivated peanut. [ABSTRACT FROM AUTHOR]

High oleic acid peanut (HOAP) is extensively embraced in China because of its high nutritional value and enhanced oxidative stability. However, its dissemination has been severely constrained in high altitude and high latitude areas due to chilling stress during sowing, resulting in significant yield loss in these regions. Despite the lack of understanding of the molecular mechanisms underlying low temperature germination (LTG) in HOAP, discovering the quantitative trait loci (QTL) that confer this trait will undoubtedly benefit breeding efforts. In the present study, we identified putative genomic regions and single nucleotide polymorphisms (SNPs) that govern LTG tolerance of HOAP in an F2 population derived from the cross of chilling-tolerant YH65 and chilling-sensitive FL14 using bulk segregant analysis (BSA). Analysis of ΔSNP-index and Euclidean distance (ED) value association pinpointed the overlapped region to a 2.29 Mb interval on chromosome A05. The candidate interval showed that 122 genes were significantly related to response to abiotic stress and plant–pathogen interaction. Furthermore, an SNP site associated with LTG tolerance was discovered. The SNP site was employed as a Kompetitive Allele Specific PCR (KASP) marker and validated in a universal peanut panel. These findings may provide valuable insight into the molecular mechanism underpinning LTG tolerance and facilitate marker-assisted selective breeding in HOAP. [ABSTRACT FROM AUTHOR]

Peanut (Arachis hypogaea) is an important economic crop that is susceptible to various foliar diseases. Web blotch, which is caused by Phoma arachidicola, is one of the most serious peanut foliar diseases because it affects the leaves and results in substantial yield losses. In this study, the P. arachidicola infection process and the response of peanut plants to infection were revealed through a cytological study of resistant and susceptible peanut varieties. Conidial germination rates, appressorium formation and resistance responses, including papillae formation and the hypersensitive response (HR), were analysed at different infection stages. Notably, the basal infection response of susceptible varieties resulted in limited papillae formation and a single HR, which was followed by programmed cell death. The papillae formation frequency and HR frequency were significantly greater in the resistant varieties than in the susceptible varieties at 84 h postinoculation. The primary difference between the two resistant varieties was the superior HR of Zheng8903 compared with that of Yuhua15. The complex amphidiploid peanut genome may explain the complexity and diversity of the resistance responses. The interactions of functional orthologs should be clarified and perhaps modulated in future investigations. The results of this study revealed the differences in the resistance responses among peanut germplasm and may be relevant for the breeding of new peanut varieties highly resistant to P. arachidicola. [ABSTRACT FROM AUTHOR]

The aim of this retrospective study was to evaluate the safety and efficacy of SEAM regimen followed by auto-SCT in lymphoma. We retrospectively reviewed the records of patients with lymphoma who underwent auto-SCT with SEAM conditioning regimen from January 2010 to June 2018 at our centre. In total, 97 patients were analysed. The median time to neutrophil engraftment and platelet engraftment was 9.5 days (range, 7–15 days) and 12 days (range, 7–25 days), respectively. Grade 3–4 nausea/vomiting, mucositis and diarrhoea were observed in 21.6%, 36.1%, and 11.3% of patients, respectively. Treatment-related mortality at 100 days occurred in 2 patients (2.1%). After a median follow-up time of 53.9 months, the 3-year incidence of disease relapse or progression was 34%. The estimated progression-free survival and overall survival at 3 years were 62% and 75%, respectively. Compared with previous studies using BEAM as the conditioning regimen, this study shows that the SEAM regimen has a comparable efficacy and safety profile. The SEAM regimen is feasible and might be an ideal alternative to BEAM regimen for lymphoma auto-SCT. [ABSTRACT FROM AUTHOR]

The gibberellic acid-stimulated Arabidopsis (GASA) gene family is essential for plant growth and development, hormone level control, and phytohormone signal transmission. Different plants have been shown to contain numerous GASA homologs. However, there is no knowledge about these proteins in peanuts. In the current study, we performed a thorough bioinformatics and expression analysis and found 20, 22, and 40 GASA genes by genome-wide analyses of A. hypogaea L., A. duranensis, and A. ipaensis, respectively. We analyzed and predicted the physical properties of these genes. Based on the results of our phylogenetic analysis, the evolutionary tree constructed from the 40 AhGASA proteins was divided into seven categories, forming a total of 14 gene pairs. According to our observations, tandem duplication is a significant factor in the expansion of the GASA gene family. AhGASA was unevenly distributed on 20 chromosomes, and 17 tandem duplicated genes were identified. A co-lineage analysis with the A/B subgenome identified 69 linear/parallel homologous gene pairs. A cis-element analysis revealed that the AhGASA protein is crucial for hormone responsiveness. In materials with different size traits at various stages of peanut pod development, transcriptomics and RT-qPCR analyses revealed that AhGASA genes are expressed at various levels and are tissue-specific. This finding suggests that some AhGASA genes may be involved in controlling peanut pod size. This study suggests that GASA genes are crucial for controlling the development of peanut pods and provides the first systematic identification and analysis of GASA genes in peanut. These findings will help future research into the function of the GASA gene in the cultivated peanut. [ABSTRACT FROM AUTHOR]

In summary, we described two cases of patients with symptoms resembling APL carrying the recurrent I NUP98-RARG i fusion but lacking a response to ATRA and/or ATO induction. (A) Bone-marrow morphology of the patient at initial diagnosis; (B) bone-marrow morphology of the patient after one course of chemotherapy; (C) G-banded karyotyping of the patient with 46,XY,add(1)(p22),? Identification of a recurrent fusion NUP98-RARG in acute myeloid leukaemia resembling acute promyelocytic leukaemia Acute promyelocytic leukaemia (APL) is a distinctive acute myeloid leukaemia (AML) subtype, which is triggered by a I PML i - I RARA i fusion caused by t(15,17)(q24;q21) translocation; the I PML i - I RARA i fusion has been proved to be a typical genetic marker in about 95% of the cases ofAPL.1 Recently, more and more cases of a morphology resembling APL carrying I RARG i fusions ( I NUP98-RARG i , I PML i - I RARG i , I CPSF6 i - I RARG i , I NPM1 i - I RARG i - I NPM1 i and I HNRNPC i - I RARG i ) without I RARA i rearrangements have been reported.2-6 I RARG i (retinoic acid receptor ), whose gene is located at chromosome 12q13, belongs to the RAR family, and acts as one of the retinoic acid receptors, and is highly homologous (90%) with RARA (retinoic acid receptor ) and RARB (retinoic acid receptor ).7 I RARA i -associated fusions are known to be associated with APL or atypical APL, but I RARG i fusions are rare. [Extracted from the article]

The peanut rich in oleic acid in seed oil, also known as high oleic peanut, renders its products superior in human healthy diet, long shelf life and high oxidative stability in food and oil processing. High oleic peanut varieties in China are derived from a handful of high oleic donors with limited genetic background. Improvement of high oleic peanut cultivars by integrating key target traits is crucial for both food security and germplasm enhancement. Several superior high oleic peanut lines have been developed by marker assisted backcrossing in our breeding program. The objective of present study is to characterize bacterial wilt disease resistance and yield related traits in these novel peanut lines. The two-year disease nursery survival rates were used as an indicator for bacterial wilt resistance, and the diagnostic markers identified by QTL mapping were used for molecular verification. Genetic background of high oleic peanut lines was estimated by 40 K genotyping by target sequencing (GBTS) SNP panel. Preliminary and regional yield tests were performed for selected breeding lines in 2021. As a result, an elite high oleic peanut accession Yuhua183 was identified, inheriting the superior characteristics of its recurrent parent such as resistance to bacterial wilt, high shelling percentage and early maturity. The development of Yuhua183 broadened the genetic background of high oleic peanut germplasm, providing valuable genetic resources for peanut breeding and further utilization. [ABSTRACT FROM AUTHOR]

Background: Patients with refractory central nervous system leukemia (CNSL) have a dismal prognosis and lack effective therapy. Case reports have shown that sorafenib is effective against brain metastases, including leukemia. Methods: To explore the efficacy of sorafenib combined with conventional therapies for refractory CNSL, a phase 2 study was conducted. The primary end point was the complete remission rate (CRR) within 8 weeks of treatment. Secondary end points included the overall response rate (ORR), event‐free survival (EFS), overall survival (OS), and adverse events (AEs). Results: Twenty‐six patients with refractory CNSL were enrolled; they included 17 with isolated CNSL, 7 with hematological relapse, and 2 with another extramedullary relapse. After 8 weeks of treatment, 21 patients achieved complete remission, 2 achieved partial remission, and 3 achieved no remission for a CRR of 80.8% (95% CI, 62.1%‐91.5%) and an ORR of 88.5% (95% CI, 71.0%‐96.0%). Twenty patients survived, and 6 died. The 2‐year EFS and OS rates were 75.0% (95% CI, 54.5%‐88.3%) and 76.9% (95% CI, 54.2%‐90.4%), respectively. Six patients experienced grade 3 or 4 treatment‐related AEs, including moderate chronic graft‐vs‐host disease (n = 3), grade 3 or 4 acute graft‐vs‐host disease (n = 2), and grade 3 skin rash (n = 1). No treatment‐related deaths occurred during the therapy of refractory CNSL. Conclusions: Sorafenib combined with conventional therapies is effective and safe for refractory CNSL. Lay Summary: Sorafenib combined with conventional therapies is effective and safe for refractory central nervous system leukemia. Sorafenib combined with conventional therapies is effective and safe for refractory central nervous system leukemia. [ABSTRACT FROM AUTHOR]

Key message: A major QTL, qBWA12, was fine mapped to a 216.68 kb physical region, and A12.4097252 was identified as a useful KASP marker for breeding peanut varieties resistant to bacterial wilt. Bacterial wilt, caused by Ralstonia solanacearum, is a major disease detrimental to peanut production in China. Breeding disease-resistant peanut varieties is the most economical and effective way to prevent the disease and yield loss. Fine mapping the QTLs for bacterial wilt resistance is critical for the marker-assisted breeding of disease-resistant varieties. A recombinant inbred population comprising 521 lines was used to construct a high-density genetic linkage map and to identify QTLs for bacterial wilt resistance following restriction-site-associated DNA sequencing. The genetic map, which included 5120 SNP markers, covered a length of 3179 cM with an average marker distance of 0.6 cM. Four QTLs for bacterial wilt resistance were mapped on four chromosomes. One major QTL, qBWA12, with LOD score of 32.8–66.0 and PVE of 31.2–44.8%, was stably detected in all four development stages investigated over the 3 trial years. Additionally, qBWA12 spanned a 2.7 cM region, corresponding to approximately 0.4 Mb and was fine mapped to a 216.7 kb region by applying KASP markers that were polymorphic between the two parents based on whole-genome resequencing data. In a large collection of breeding and germplasm lines, it was proved that KASP marker A12.4097252 can be applied for the marker-assisted breeding to develop peanut varieties resistant to bacterial wilt. Of the 19 candidate genes in the region covered by qBWA12, nine NBS-LRR genes should be further investigated regarding their potential contribution to the resistance of peanut against bacterial wilt. [ABSTRACT FROM AUTHOR]

• CoMn-LDH/ZIF-67/PANI with network structure was prepared. • The influence of CoMn-LDH on the stability of ZIF-67 was discussed. • The influence of PANI on the conductivity of CoMn-LDH/ZIF-67 was explored. • The specific capacitance of CoMn-LDH/ZIF-67/PANI can reach 1048 F g−1 at 1 A g−1. Metal-organic framework materials (MOFs) are widely used in electrochemical energy storage due to their abundant active sites and high redox activity. Especially in the field of supercapacitors, the porous structure of MOFs makes them the most promising candidates for composite electrode materials due to their vast specific surface area. However, the poor chemical stability of MOFs in alkaline electrolytes limits their application. Constructing and improving the stability of metal-organic backbone materials through rational structural design is the key to enhancing the electrochemical performance of capacitors. In this paper, the stability of ZIF-67 was enhanced by the complexing with bimetallic hydroxide (CoMn-LDH), and the conductivity is further enhanced by the mixing of polyaniline (PANI) to form a ''network structure'' morphology. As a result, the composite electrode material has a specific capacity of 1048 F g−1 at 1 A g−1 with a good cycle life (80.5 % capacity retention for 5000 cycles). The specific capacity of the CoMn-LDH/ZIF-67/PANI//AC asymmetric supercapacitor (ASC) was 164 F g−1 at 1 A g−1 in the voltage range of 0–1.5 V. The maximum energy density of the ASC was 51.25 Wh kg−1 at a power density of 2250 W kg−1. In addition, excellent cycling stability (71.2 % capacitance retention after 5000 cycles) was delivered. [Display omitted] [ABSTRACT FROM AUTHOR]

To solve the problems of difficult fault signal recognition and poor diagnosis effect of different damage in the same position in rolling mill bearing at low speed, a fault diagnosis method of rolling mill bearing based on integration of EEMD and DBN was proposed. The vibration signals in horizontal, axial, and vertical directions were decomposed and reconstructed by EEMD, and frequency domain analysis was carried out by using refined spectrum. Then, the signal's time-frequency domain index, rolling force, and torque component feature vector were input into genetic algorithm (GA) to optimize DBN model classification. In order to verify the effectiveness of the method, the experimental study was carried out on the two-high experimental rolling mill. The results show that EEMD combined with thinning spectrum can solve the problem of fault feature extraction well. Compared with time-frequency domain characteristic input, the prediction accuracy of DBN model is obviously improved. And the accuracy of GA-DBN model is higher, and the accuracy is 98.3%, and the time taken to diagnose is significantly reduced. Finally, the fault classification of different parts of bearings and the fault diagnosis of different damage in the same part are realized, which provides a good theoretical basis for the fault diagnosis of low-speed bearings and has important engineering significance. [ABSTRACT FROM AUTHOR]

Abstract: A multi-residue method developed for the analysis of triazine herbicides, simazine, atrazine, propazine and prometryne, in sheep liver is presented. The method is based on microwave-assisted extraction (MAE) of sheep liver using methanol as extractant and analysis of extracts by high performance liquid chromatography (HPLC) and ultraviolet detection. MAE operational parameters, the solvent type and volume, extraction temperature and time, were optimized in detail with respect to extraction efficiency of the target compounds from sheep liver. The recoveries of the method at two different spiked levels were assessed by analyzing spiked liver samples and were found to be in the range from 90 to 102% with good precision (<11%). [Copyright &y& Elsevier]

Peanut shell plays key roles in protecting the seed from diseases and pest infestation but also in the processing of peanut and is an important byproduct of peanut production. Most studies on peanut shell have focused on the utilization of its chemical applications, but the genetic basis of shell-related traits is largely unknown. A panel of 320 peanut (Arachis hypogaea) accessions including var. hypogaea, var. vulgaris, var. fastigiata and var. hirsuta was used to study the genetic basis of two physical and five microstructure-related traits in peanut shell. Significant phenotypic differences were revealed among the accessions of var. hypogaea, var. hirsuta, var. vulgaris and var. fastigiata for mechanical strength, thickness, three sclerenchymatous layer projections and main cell shape of the sclerenchymatous layer. We identified 10 significant single nucleotide polymorphisms (SNPs) through genome-wide association study (P < 5.0 × 10−6) combining the shell-related traits and high-quality SNPs. In total, 192 genes were located in physical proximity to the significantly associated SNPs, and 11 candidate genes were predicted related to their potential contribution to the development and structure of the peanut shell. All SNPs were detected on the B genome demonstrating the biased contribution of the B genome for the phenotypical make-up of peanut. Exploring the newly identified candidate genes will provide insight into the molecular pathways that regulate peanut shell-related traits and provide valuable information for molecular marker-assisted breeding of an improved peanut shell. [ABSTRACT FROM AUTHOR]

Background: Chromosomal variants play important roles in crop breeding and genetic research. The development of single-stranded oligonucleotide (oligo) probes simplifies the process of fluorescence in situ hybridization (FISH) and facilitates chromosomal identification in many species. Genome sequencing provides rich resources for the development of oligo probes. However, little progress has been made in peanut due to the lack of efficient chromosomal markers. Until now, the identification of chromosomal variants in peanut has remained a challenge. Results: A total of 114 new oligo probes were developed based on the genome-wide tandem repeats (TRs) identified from the reference sequences of the peanut variety Tifrunner (AABB, 2n = 4x = 40) and the diploid species Arachis ipaensis (BB, 2n = 2x = 20). These oligo probes were classified into 28 types based on their positions and overlapping signals in chromosomes. For each type, a representative oligo was selected and modified with green fluorescein 6-carboxyfluorescein (FAM) or red fluorescein 6-carboxytetramethylrhodamine (TAMRA). Two cocktails, Multiplex #3 and Multiplex #4, were developed by pooling the fluorophore conjugated probes. Multiplex #3 included FAM-modified oligo TIF-439, oligo TIF-185-1, oligo TIF-134-3 and oligo TIF-165. Multiplex #4 included TAMRA-modified oligo Ipa-1162, oligo Ipa-1137, oligo DP-1 and oligo DP-5. Each cocktail enabled the establishment of a genome map-based karyotype after sequential FISH/genomic in situ hybridization (GISH) and in silico mapping. Furthermore, we identified 14 chromosomal variants of the peanut induced by radiation exposure. A total of 28 representative probes were further chromosomally mapped onto the new karyotype. Among the probes, eight were mapped in the secondary constrictions, intercalary and terminal regions; four were B genome-specific; one was chromosome-specific; and the remaining 15 were extensively mapped in the pericentric regions of the chromosomes. Conclusions: The development of new oligo probes provides an effective set of tools which can be used to distinguish the various chromosomes of the peanut. Physical mapping by FISH reveals the genomic organization of repetitive oligos in peanut chromosomes. A genome map-based karyotype was established and used for the identification of chromosome variations in peanut following comparisons with their reference sequence positions. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) infection of the central nervous system (CNS) is a rare but life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Cases presentation: Two patients with drug-resistant CMV encephalitis after allo-HSCT were successfully treated with donor CMV-specific cytotoxic T lymphocytes (CTLs). In the first case, a 27-year-old male who received haploidentical transplantation to treat T-cell acute lymphoblastic leukemia (T-ALL), developed CMV encephalitis during the time of the ganciclovir maintenance treatment. After intravenous foscarnet and donor CMV-specific CTLs, CMV-DNA of CSF became undetectable and the abnormal signs of brain magnetic resonance imaging (MRI) were limited. Another case, a 57-year-old female with acute myeloid leukemia (AML) who underwent haploidentical transplantation, also developed CMV encephalitis during the maintenance treatment of the ganciclovir. After administering donor CMV-specific CTLs intrathecally, the CMV load of the CSF decreased. Conclusions: The intravenous/intratheca administration of donor CMV-specific CTLs may be a safe and effective treatment for CMV encephalitis, especially for patients who suffered from drug-resistant CMV infection. [ABSTRACT FROM AUTHOR]

Cytosolic acetyl-CoA is an intermediate of the synthesis of most secondary metabolites and the source of acetyl for protein acetylation. The formation of cytosolic acetyl-CoA from citrate is catalysed by ATP-citrate lyase (ACL). However, the function of ACL in global metabolite synthesis and global protein acetylation is not well known. Here, four genes, PaACLA1 , PaACLA2 , PaACLB1 , and PaACLB2 , which encode the ACLA and ACLB subunits of ACL in Petunia axillaris , were identified as the same sequences in Petunia hybrida 'Ultra'. Silencing of PaACLA1-A2 and PaACLB1-B2 led to abnormal leaf and flower development, reduced total anthocyanin content, and accelerated flower senescence in petunia 'Ultra'. Metabolome and acetylome analysis revealed that PaACLB1-B2 silencing increased the content of many downstream metabolites of acetyl-CoA metabolism and the levels of acetylation of many proteins in petunia corollas. Mechanistically, the metabolic stress induced by reduction of acetyl-CoA in PaACL -silenced petunia corollas caused global and specific changes in the transcriptome, the proteome, and the acetylome, with the effect of maintaining metabolic homeostasis. In addition, the global proteome and acetylome were negatively correlated under acetyl-CoA deficiency. Together, our results suggest that ACL acts as an important metabolic regulator that maintains metabolic homeostasis by promoting changes in the transcriptome, proteome. and acetylome. [ABSTRACT FROM AUTHOR]

The Sanz risk, which was originally used to predict the risk of acute promyelocytic leukemia (APL) relapse, is a recognized method to predict the prognosis of APL. About 570 de novo APL patients admitted to our center were randomly divided into a training cohort (N = 344) and validation cohort (N = 226). Multivariate analysis of training cohort demonstrated that age >52 (OR = 5.170, p =.002), white blood cell count >10 × 109/L (OR = 9.062, p <.001), PLT count ≤10 × 109/L (OR = 4.254, p <.001), and LDH level >500 U/L (OR= 3.002, p =.046) were independent risk factors for early death. A risk score (age >52: 1.5 points; WBC >10 × 109/L: 2 points; PLT ≤10 × 109/L: 1 point; LDH >500 U/L: 1 point) was used to predict early death risk. The model shows a better predictive power of early death in training cohort and validation cohort compared with Sanz risk stratification. [ABSTRACT FROM AUTHOR]

Key message: Groundnut has entered now in post-genome era enriched with optimum genomic and genetic resources to facilitate faster trait dissection, gene discovery and accelerated genetic improvement for developing climate-smart varieties. Cultivated groundnut or peanut (Arachis hypogaea), an allopolyploid oilseed crop with a large and complex genome, is one of the most nutritious food. This crop is grown in more than 100 countries, and the low productivity has remained the biggest challenge in the semiarid tropics. Recently, the groundnut research community has witnessed fast progress and achieved several key milestones in genomics research including genome sequence assemblies of wild diploid progenitors, wild tetraploid and both the subspecies of cultivated tetraploids, resequencing of diverse germplasm lines, genome-wide transcriptome atlas and cost-effective high and low-density genotyping assays. These genomic resources have enabled high-resolution trait mapping by using germplasm diversity panels and multi-parent genetic populations leading to precise gene discovery and diagnostic marker development. Furthermore, development and deployment of diagnostic markers have facilitated screening early generation populations as well as marker-assisted backcrossing breeding leading to development and commercialization of some molecular breeding products in groundnut. Several new genomics applications/technologies such as genomic selection, speed breeding, mid-density genotyping assay and genome editing are in pipeline. The integration of these new technologies hold great promise for developing climate-smart, high yielding and more nutritious groundnut varieties in the post-genome era. [ABSTRACT FROM AUTHOR]

Objectives: Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by CCND1/IGH rearrangement. We reported a case of MCL harboring both CCND1/IGH and MYC/IGH rearrangements that also presented with an aggressive clinical course.Methods: Biopsy specimens were evaluated by morphological staining, immunohistochemistry, flow cytometry, conventional cytogenetics, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS).Results: Morphological and immunohistochemical staining of gallbladder samples demonstrated blastoid variant MCL. However, in the bone marrow sample, FISH indicated rearrangements in CCND1/IGH and MYC/IGH. Flow cytometry identified two groups of malignant lymphocytes. We sorted these two groups of cells. NGS then revealed that both cell types carried CCND1/IGH rearrangements and TP53 mutations. Furthermore, the CD19+/CD10+ cells carried additional MYC/IGH rearrangement and NOTCH2 mutation.Conclusions: The rearrangement of MYC and a mutation in NOTCH2 probably induced the transformation of MCL cells in this patient. This uncommon double-hit MCL case clearly demonstrates a transformation process. [ABSTRACT FROM AUTHOR]

Forty-three chromosomal abnormalities in Philadelphia-negative metaphases (Ph–CAs) appeared in 35 of 432 patients in chronic phase chronic myeloid leukemia (CP-CML) undergoing tyrosine kinase inhibitor (TKI) treatments. These CAs were mostly common in trisomy-8 (16 cases), trisomy-Y (five cases), and monosomy-7 (five cases). Furthermore, Ph– CAs were significantly associated with higher platelet count (494 × 109/L vs. 326 × 109/L, p =.006), and higher incidence of true clonal evolution in Ph-positive metaphase (22.9% vs. 9.1%, p =.017). Additionally, patients with Ph– CAs had worse rates of complete cytogenetic remission (76% vs. 86%, p =.0091), major molecular remission (55% vs. 76%, p =.001), progression-free survival (47% vs. 86%, p <.001), but a similar overall survival rates compared to those in patients without Ph– CAs. In conclusion, Ph– CAs may predict worse response to TKI therapies and survival in patients with CP-CML, thus requiring close cytogenetic monitoring. [ABSTRACT FROM AUTHOR]

Central nervous system complications (CNSCs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are common and may be a significant source of morbidity and mortality. We performed a retrospective study of 153 pediatric patients who underwent allo-HSCT to determine CNSC type, incidence, and impact on survival. A total of 34 patients (22.2%) developed CNSCs. The cumulative incidence of CNSCs at 100 days and 3 years was 18.30 and 22.73%, respectively. The most common CNSC was calcineurin inhibitor (CNI)-associated neurotoxicity (50.0%). Risk factors for CNSCs were the time from diagnosis to HSCT ≥4.8 months (p = 0.032) and the development of acute graft-versus-host disease (aGVHD) grade III–IV (p = 0.002). CNSCs after allo-HSCT negatively impacted overall survival (hazard ratio [HR] 1.97, p = 0.043) and nonrelapse mortality (HR 4.84, p < 0.001). In conclusion, CNSCs after allo-HSCT are associated with poor outcomes; patients with severe aGVHD and/or late transplantation should be given more attention. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a fatal hematopoietic malignancy with poor clinical outcomes. To determine whether the expression of the long non-coding (lnc)RNA zinc finger E-box binding homeobox 2 (ZEB2) antisense RNA 1 (ZEB2-AS1) is associated with clinical outcomes, its expression was analyzed in a retrospective cohort of 62 AML and 10 non-malignant cases. The results revealed that the expression of ZEB2-AS1 lncRNA was notably high and closely associated with adverse clinical outcomes in AML cases compared with the non-malignant cases, based on either modified Medical Research Council or European Leukemia Net risk stratification systems. Univariate analyses indicated that patients with a higher expression of ZEB2-AS1 lncRNA had significantly shorter overall survival (OS) (P=0.036) and disease-free survival (DFS) rates (P=0.039) compared with patients with a lower expression of ZEB2-AS1 lncRNA. In addition, patients with a higher expression of ZEB2-AS1 lncRNA had a significant lower complete remission rate in response to induction by chemotherapy compared with patients with a lower expression of ZEB2-AS1 lncRNA (P=0.031). In cases with low levels of ZEB2-AS1 lncRNA, patients treated with allogenic hematopoietic stem cell transplantation had significantly longer OS and DFS rates compared with that of chemotherapy-treated patients (P=0.037 and P=0.049 respectively). Furthermore, the knockdown of ZEB2-AS1 lncRNA effectively inhibited AML cell invasion and migration, which was closely associated with the downregulation of ZEB2 and upregulation of E-cadherin expression. Collectively, although its independent prognostic value for survival was not rigorously determined, ZEB2-AS1 lncRNA may function as a candidate marker to improve conventional risk stratification systems and the evaluation of therapeutic responses for AML. [ABSTRACT FROM AUTHOR]

The aim of this study is to determine whether the modified BuCy (semustine, cytarabine, busulfan, and cyclophosphamide, mBuCy) conditioning regimen can be safely used as an alternative to the SEAM (semustine, etoposide, cytarabine, and melphalan) regimen by comparing the efficacy and toxicity of the mBuCy and SEAM regimens. We matched 34 pairs of patients with regard to disease status at the time of autologous stem cell transplantation (auto-SCT). We found no significant difference in the time of platelet engraftment between the two groups. Furthermore, neutrophil engraftment was somewhat faster in the mBuCy group than in the SEAM group (median: 9 days vs 10 days, p = 0.015). With regard to toxicity, the incidence of nausea/vomiting, hepatic impairment, renal impairment, pulmonary infection, and treatment-related mortality (TRM) was similar between the two groups. In addition, compared to patients conditioned with SEAM, patients conditioned with mBuCy were less likely to develop mucositis and diarrhea (p = 0.027; p = 0.050). The 2-year progression-free survival (PFS) rates in the mBuCy and SEAM groups were 79% and 70% (p = 0.378), respectively, and the 2-year overall survival (OS) rates were 81% and 78.0%, respectively (p = 0.789). These analyses showed that the mBuCy conditioning regimen was well tolerated and can be used as an alternative to the SEAM regimen for lymphoma. [ABSTRACT FROM AUTHOR]

Purpose: Multiple myeloma (MM) remains incurable. The MM microenvironment supports MM cells' survival and immune escape. Because myeloid-derived suppressor cells (MDSCs) is important in the MM microenvironment, and demethylating agent decitabine (DAC) can deplete MDSCs in vitro and in vivo, we hypothesized that DAC treatment could inhibit MM by depleting MDSCs in the MM microenvironment.Methods: In this study, we used the mouse IL6 secreting, myeloma cell line MPC11 as a model. MDSCs were sorted using magnetic beads and cultured. A transwell coculture assay was used to mimic the microenvironment in vitro. And MPC11-bearing mice model was used to observe the efficacy of DAC treatment in vivo.Results: In vitro coculture assay indicated that MPC11 cells showed significantly lower proliferation rate, less IL6 production and more apoptosis when they were cocultured with bone marrow cells without MDSCs (nonMDSCs) or DAC-treated bone marrow cells (DAC BMs) than with MDSCs or PBS-treated bone marrow cells (CTR BM). Supplementation with M-MDSCs rescued the inhibitory effect of DAC BMs, while additional NOHA supplementation further antagonized the rescue effect of M-MDSCs. In MPC11-bearing mice, the combined treatment of DAC with anti-Gr1 antibody showed synergistic effect on inhibiting tumor growth and promoting T cell infiltration in the tumor tissue. M-MDSC reinfusion also antagonized the efficacy of DAC treatment.Conclusions: DAC treatment can inhibit myeloma cell proliferation and induce enhanced autologous T cell immune response by depleting M-MDSCs in the MM microenvironment. We believe that DAC treatment could improve the prognosis of MM in future. [ABSTRACT FROM AUTHOR]

Late leaf spot (LLS) is a major foliar disease in peanut (A. hypogaea L.) worldwide, causing significant losses of potential yield in the absence of fungicide applications. Mutants are important materials to study the function of disease-related genes. In this study, the mutant line M14 was derived from cultivar Yuanza 9102 treated with EMS. Yuanza 9102 was selected from an interspecific cross of cultivar Baisha 1016 with A. diogoi, and is resistant to several fungal diseases. By contrast, the M14 was highly susceptible to late leaf spot. RNA-Seq analysis in the leaf tissues of the M14 and its wild type Yuanza 9102 under pathogen challenge showed 2219 differentially expressed genes including1317 up-regulated genes and 902 down-regulated genes. Of these genes, 1541, 1988, 1344, 643 and 533 unigenes were obtained and annotated by public protein databases of SwissPort, TrEMBL, gene ontology (GO), KEGG and clusters of orthologous groups (COG), respectively. Differentially expressed genes (DEGs) showed that expression of inducible pathogenesis-related (PR) proteins was significantly up-regulated; in the meantime DEGs related to photosynthesis were down-regulated in the susceptible M14 in comparison to the resistant WT. Moreover, the up-regulated WRKY transcription factors and down-regulated plant hormones related to plant growth were detected in the M14. The results suggest that down-regulated chloroplast genes, up-regulated WRKY transcription factors, and depressed plant hormones related to plant growth in the M14 might coordinately render the susceptibility though there was a significant high level of PRs. Those negative effectors might be triggered in the susceptible plant by fungal infection and resulted in reduction of photosynthesis and phytohormones and led to symptom formation. [ABSTRACT FROM AUTHOR]

Purpose: The immunoregulatory effect of demethylating agent decitabine (DAC) has been recognized recently. However, little is known about its impact on immune tolerance. In this study, we aimed to determine the impact of DAC on the immune tolerance induced by tumor cells. Methods: The effects of DAC on immune cells in vivo were measured by flow cytometry. Myeloid-derived suppressor cells (MDSCs) were sorted using magnetic beads and cultured in vitro. The mixed lymphocyte reaction was used to determine the immunoregulatory effect of DAC in vitro. An adoptive transfusion mouse model was established to evaluate the effect in vivo. Results: We found that DAC treatment significantly depleted MDSCs in vivo by inducing MDSCs apoptosis. When given at a low dose, the immune effector cells were less affected by the treatment, except for MDSCs. The mixed lymphocyte reaction in vitro showed that T-cell responses were enhanced when MDSCs were depleted. Supplementation of MDSCs would attenuate this T-cell activation effect. Using an adoptive transfusion mouse model, we further demonstrated in vivo that DAC treatment could induce autologous anti-tumor immune response by depleting MDSCs. Conclusions: This study is the first to illustrate DAC's immunoregulatory effect on immune tolerance. The disruption of immune tolerance is due to MDSCs depletion that induces an autologous immune response in vivo. By depleting MDSCs, DAC treatment removes one of the obstacles affecting anti-tumor immune activation and warrants further experimental and clinical studies to explore its potential utility in combination with various anti-tumor immunotherapies in the future. [ABSTRACT FROM AUTHOR]

Background: Acute graft-versus-host disease (aGVHD) remains a major obstacle against favorable clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T helper cells including Th17 play key roles in aGVHD pathogenesis. Donor regulatory T cell (Tregs) adoptive therapy reduces aGVHD without weakening graft-versus-leukemia effect (GVL) in both mouse and human, although the purification and ex vivo expansion of Tregs in clinical scenarios remain costly and technically demanding. Hypoxia-inducible factor 1 alpha (HIF-1α) is a key molecule switch that attenuates Treg but promotes Th17 development. However, whether pharmacological inhibition of HIF-1α reduces aGVHD via increasing Treg development and diminishing Th17 responses remains unexplored.Methods: By using alloantigen-specific mixed lymphocyte culture and murine models of aGVHD and GVL, we evaluated the impacts of HIF-1α inhibition by echinomycin on the alloantigen-specific CD4 T cell responses ex vivo, as well as on aGVHD and GVL effect following allo-HSCT.Results: Ex vivo echinomycin treatment resulted in increased number of Tregs in the culture as well as reduced alloantigen-specific Th17 and Th1 responses. In vivo echinomycin treatment reduced GVHD scores and prolonged survival of mice following allo-HSCT, which is associated with increased number of donor Tregs and reduced number of Th17 and Th1 in lymphoid tissues. In murine model of leukemia, echinomycin treatment preserved GVL effect and prolonged leukemia free survival following allo-HSCT.Conclusions: Echinomycin treatment reduces aGVHD and preserves GVL effect via increasing donor Treg development and diminishing alloantigen-specific Th17 and Th1 responses following allo-HSCT, presumably via direct inhibition of HIF-1α that results in preferential Treg differentiation during alloantigen-specific CD4 T cell responses. These findings highlight pharmacological inhibition of HIF-1α as a promising strategy in GVHD prophylaxis. [ABSTRACT FROM AUTHOR]

Studies have demonstrated that nucleotide-binding site–leucine-rich repeat (NBS–LRR) genes respond to pathogen attack in plants. Characterization of NBS–LRR genes in peanut is not well documented. The newly released whole genome sequences of Arachis duranensis and Arachis ipaënsis have allowed a global analysis of this important gene family in peanut to be conducted. In this study, we identified 393 (AdNBS) and 437 (AiNBS) NBS–LRR genes from A. duranensis and A. ipaënsis, respectively, using bioinformatics approaches. Full-length sequences of 278 AdNBS and 303 AiNBS were identified. Fifty-one orthologous, four AdNBS paralogous, and six AiNBS paralogous gene pairs were predicted. All paralogous gene pairs were located in the same chromosomes, indicating that tandem duplication was the most likely mechanism forming these paralogs. The paralogs mainly underwent purifying selection, but most LRR 8 domains underwent positive selection. More gene clusters were found in A. ipaënsis than in A. duranensis, possibly owing to tandem duplication events occurring more frequently in A. ipaënsis. The expression profile of NBS–LRR genes was different between A. duranensis and A. hypogaea after Aspergillus flavus infection. The up-regulated expression of NBS–LRR in A. duranensis was continuous, while these genes responded to the pathogen temporally in A. hypogaea. [ABSTRACT FROM AUTHOR]

Cultivated peanut is grown worldwide as rich-source of oil and protein. A broad genetic base is needed for cultivar improvement. The objectives of this study were to develop highly informative simple sequence repeat (SSR) markers and to assess the genetic diversity and population structure of peanut cultivars and breeding lines from different breeding programs in China, India and the US. A total of 111 SSR markers were selected for this study, resulting in a total of 472 alleles. The mean values of gene diversity and polymorphic information content (PIC) were 0.480 and 0.429, respectively. Country-wise analysis revealed that alleles per locus in three countries were similar. The mean gene diversity in the US, China and India was 0.363, 0.489 and 0.47 with an average PIC of 0.323, 0.43 and 0.412, respectively. Genetic analysis using the STRUCTURE divided these peanut lines into two populations (P1, P2), which was consistent with the dendrogram based on genetic distance (G1, G2) and the clustering of principal component analysis. The groupings were related to peanut market types and the geographic origin with a few admixtures. The results could be used by breeding programs to assess the genetic diversity of breeding materials to broaden the genetic base and for molecular genetics studies. [ABSTRACT FROM AUTHOR]

Bacterial wilt (BW) disease is a widespread disease in peanut ( Arachis hypogaea L.), reducing peanut production because of high susceptibility of most cultivated species. However, Arachis glabrata, a perennial wild relative, has high resistance to soil-borne diseases. MicroRNAs (miRNAs) have been characterized as important factors in plant growth, development, and biotic/abiotic stress responses. However, their roles in response to pathogen are still unknown in peanut. Here, we constructed four miRNA libraries from A. hypogaea and A. glabrata and identified 155 known miRNAs, 31 novel miRNAs, and 173 plausible candidates of novel miRNAs. After infected with BW, the expression of many known miRNA was induced or inhibited in both cultivated and wild-type peanuts. Many miRNAs displayed differential expression patterns in these two species, and the expression of some miRNAs was confirmed by quantitative real-time PCR (qRT-PCR) analysis. A total of 309 targets were predicted, among which 74 of them were confirmed by degradome sequencing. More than 10 % of the targets were defense response genes, such as hypersensitive-induced response protein, leucine-rich repeat (LRR) receptor-like serine/threonine-protein kinase, GRAS, aquaporin, lipid transfer protein, ARF, MYB transcription factors, and MLP-like protein. Our results indicate that diverse set of miRNAs of cultivated and wild peanut species is responsive to BW infection and suggests a possible role in peanut disease resistance. [ABSTRACT FROM AUTHOR]

The competitiveness of peanuts in domestic and global markets has been threatened by losses in productivity and quality that are attributed to diseases, pests, environmental stresses and allergy or food safety issues. Narrow genetic diversity and a deficiency of polymorphic DNA markers severely hindered construction of dense genetic maps and quantitative trait loci (QTL) mapping in order to deploy linked markers in marker-assisted peanut improvement. The U.S. Peanut Genome Initiative (PGI) was launched in 2004, and expanded to a global effort in 2006 to address these issues through coordination of international efforts in genome research beginning with molecular marker development and improvement of map resolution and coverage. Ultimately, a peanut genome sequencing project was launched in 2012 by the Peanut Genome Consortium (PGC). We reviewed the progress for accelerated development of peanut genomic resources in peanut, such as generation of expressed sequenced tags (ESTs) (252,832 ESTs as December 2012 in the public NCBI EST database), development of molecular markers (over 15,518 SSRs), and construction of peanut genetic linkage maps, in particular for cultivated peanut. Several consensus genetic maps have been constructed, and there are examples of recent international efforts to develop high density maps. An international reference consensus genetic map was developed recently with 897 marker loci based on 11 published mapping populations. Furthermore, a high-density integrated consensus map of cultivated peanut and wild diploid relatives also has been developed, which was enriched further with 3693 marker loci on a single map by adding information from five new genetic mapping populations to the published reference consensus map. [ABSTRACT FROM AUTHOR]