Lipid catabolism in germinating seeds provides energy and substrates for initial seedling growth, but how this process is regulated is not well understood. Here, we show that an AT-hook ...motif-containing nuclear localized (AHL) protein regulates lipid mobilization and fatty acid β-oxidation during seed germination and seedling establishment. AHL4 was identified to directly interact with the lipid mediator phosphatidic acid (PA). Knockout (KO) of AHL4 enhanced, but overexpression (OE) of AHL4 attenuated, triacylglycerol (TAG) degradation and seedling growth. Normal seedling growth of the OE lines was restored by sucrose supplementation to the growth medium. AHL4-OE seedlings displayed decreased expression of genes involved in TAG hydrolysis and fatty acid oxidation, whereas the opposite was observed in AHL4-KOs. These genes contained AHL4-binding cis elements, and AHL4 was shown to bind to the promoter regions of genes encoding the TAG lipases SDP1 and DALL5 and acyl-thioesterase KAT5. These AHL4–DNA interactions were suppressed by PA species that bound to AHL4. These results indicate that AHL4 suppresses lipid catabolism by repressing the expression of specific genes involved in TAG hydrolysis and fatty acid oxidation, and that PA relieves AHL4-mediated suppression and promotes TAG degradation. Thus, AHL4 and PA together regulate lipid degradation during seed germination and seedling establishment.
This study shows that the transcription factor AHL4 (AT-hook motif-containing nuclear localized 4) suppresses the expression of specific genes involved in triacylglycerol (TAG) hydrolysis and fatty acid β-oxidation, whereas phosphatidic acid (PA), the glycerolipid metabolic intermediate and cellular mediator, binds to AHL4 and relieves the transcriptional suppression. Thus, PA and AHL4 together regulate TAG and fatty acid catabolism during seed germination and seedling establishment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
OBJECTIVESThe role of subcutaneous (SC) rituximab in the efficacy and safety to non-Hodgkin lymphoma (NHL) is not clear enough. The purpose of this study was to conduct a systematic review and ...meta-analysis, to assess the efficacy and safety of subcutaneous rituximab to NHL.METHODA full-scale search was carried out based on the set search terms in PubMed, Web of Science, Embase and Cochrane CENTRAL until 12 October 2022 to identify relevant studies of subcutaneous rituximab for NHL. The efficacy and safety outcomes included complete response (CR) plus unconfirmed complete response (CRu), adverse events (AEs), grade ≥3 AEs, serious adverse events (SAEs), administration-related reactions (ARRs), adverse reaction rates.RESULTSFrom a total of 758 studies, 9 trials were eligible. The CR/CRu of patients with NHL receiving SC rituximab was 57%, 55% for Diffuse large B-cell lymphoma (DLBCL) and 54% for Follicular lymphoma (FL). The meta-analysis performed on safety demonstrated that AEs of NHL patients with SC rituximab was 85%, grade ≥3 AEs was 38%, SAE was 27% and ARR was 33%. The result also showed that SC rituximab had a high risk of neutropenia and nausea.CONCLUSIONFor NHL patients, there is no significant difference in the efficacy between subcutaneous rituximab and conventional therapy, while subcutaneous injection can shorten exposure time in the hospital and reduce the risk of infection.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Stem rot caused by Sclerotinia sclerotiorum in many important dicotyledonous crops, including oilseed rape (Brassica napus), is one of the most devastating fungal diseases and imposes huge yield loss ...each year worldwide. Currently, breeding for Sclerotinia resistance in B. napus, as in other crops, can only rely on germplasms with quantitative resistance genes. Thus, the identification of quantitative trait locus (QTL) for S. sclerotiorum resistance/tolerance in this crop holds immediate promise for the genetic improvement of the disease resistance. In this study, ten QTLs for stem resistance (SR) at the mature plant stage and three QTLs for leaf resistance (LR) at the seedling stage in multiple environments were mapped on nine linkage groups (LGs) of a whole genome map for B. napus constructed with SSR markers. Two major QTLs, LRA9 on LG A9 and SRC6 on LG C6, were repeatedly detected across all environments and explained 8.54-15.86% and 29.01%-32.61% of the phenotypic variations, respectively. Genotypes containing resistant SRC6 or LRA9 allele showed a significant reduction in disease lesion after pathogen infection. Comparative mapping with Arabidopsis and data mining from previous gene profiling experiments identified that the Arabidopsis homologous gene of IGMT5 (At1g76790) was related to the SRC6 locus. Four copies of the IGMT5 gene in B. napus were isolated through homologous cloning, among which, only BnaC.IGMT5.a showed a polymorphism between parental lines and can be associated with the SRC6. Furthermore, two parental lines exhibited a differential expression pattern of the BnaC.IGMT5.a gene in responding to pathogen inoculation. Thus, our data suggested that BnaC.IGMT5.a was very likely a candidate gene of this major resistance QTL.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Vegetable oil is an essential constituent of the human diet and renewable raw material for industrial applications. Enhancing oil production by increasing seed oil content in oil crops is the most ...viable, environmentally friendly, and sustainable approach to meet the continuous demand for the supply of vegetable oil globally. An in-depth understanding of the gene networks involved in oil biosynthesis during seed development is a prerequisite for breeding high-oil-content varieties. Rapeseed (
) is one of the most important oil crops cultivated on multiple continents, contributing more than 15% of the world's edible oil supply. To understand the phasic nature of oil biosynthesis and the dynamic regulation of key pathways for effective oil accumulation in
, comparative transcriptomic profiling was performed with developing seeds and silique wall (SW) tissues of two contrasting inbred lines with ~13% difference in seed oil content. Differentially expressed genes (DEGs) between high- and low-oil content lines were identified across six key developmental stages, and gene enrichment analysis revealed that genes related to photosynthesis, metabolism, carbohydrates, lipids, phytohormones, transporters, and triacylglycerol and fatty acid synthesis tended to be upregulated in the high-oil-content line. Differentially regulated DEG patterns were revealed for the control of metabolite and photosynthate production in SW and oil biosynthesis and accumulation in seeds. Quantitative assays of carbohydrates and hormones during seed development together with gene expression profiling of relevant pathways revealed their fundamental effects on effective oil accumulation. Our results thus provide insights into the molecular basis of high seed oil content (SOC) and a new direction for developing high-SOC rapeseed and other oil crops.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Sclerotinia stem rot (SSR) caused by the necrotrophic fungus
is a major disease in rapeseed (
) worldwide. Breeding for SSR resistance in
, as in other crops, relies only on germplasms with ...quantitative resistance genes. A better understanding of the genetic basis for SSR resistance in
thus holds promise for the genetic improvement of disease resistance. In the present study, a genome-wide association study (GWAS) for SSR resistance in
were performed using an association panel of 448 accessions genotyped with the
60K Infinium
single-nucleotide polymorphism (SNP) array. A total of 26 SNPs corresponding to three loci,
,
, and
were associated with SSR resistance. Haplotype analysis showed that the three favorable alleles for SSR resistance exhibited cumulative effects. After aligning SSR resistance quantitative trait loci (QTL) identified in the present and previous studies to the
reference genome, one locus (
) was found to be located within the confidence interval of a QTL identified in previous QTL mapping studies and another two loci (
and
) were considered novel loci for SSR resistance. A total of 39 candidate genes were predicted for the three loci based on the GWAS combining with the differentially expressed genes identified in previous transcriptomics analyses.
Long noncoding RNAs (lncRNAs) are known to play a key role in chronic myelocytic leukemia (CML) development, and we aimed to identify the involvement of the lncRNA HOX antisense intergenic RNA ...(HOTAIR) in CML via binding to DNA methyltransferase 1 (DNMT1) to accelerate methylation of the phosphatase and tensin homolog (PTEN) gene promoter. Bone marrow samples from CML patients and normal bone marrow samples from healthy controls were collected. HOTAIR, DNMT1, DNMT3A, DNMT3B, and PTEN expression was detected. The biological characteristics of CML cells were detected. The relationship among HOTAIR, DNMT1, and PTEN was verified. Tumor volume and weight in mice injected with CML cells were tested. We found that HOTAIR and DNMT1 expression was increased and PTEN expression was decreased in CML. We also investigated whether downregulated HOTAIR or DNMT1 reduced proliferation, colony formation, invasion, and migration and increased the apoptosis rate of CML cells. Moreover, we tested whether low expression of HOTAIR or DNMT1 reduced the volume and weight of tumors in mice with CML. Collectively, the results of this studied showed that depleted HOTAIR demonstrated reduced binding to DNMT1 to suppress CML progression, which may be related to methylation of the PTEN promoter.
Lithium and its related products are important materials in modern society. A large amount of energy is consumed for the extracting or concentrating lithium salts from primary resources. In this ...study, electrodialysis (ED) was introduced to concentrate Li2SO4 solution. Effects of ion exchange membrane type, applied voltage drop across the ED stack, and especially the operating mode were investigated. Results indicated that Neosepta AMX/CMX membranes were more preferable than FKS/FAS and CJMC/MA membranes for lithium salt concentrating at the voltage drop of 6V. Additionally, it's found that the volume ratio of 1:3 was optimal choice for two-stage ED. The final Li2SO4 concentration could reach as high as 17.4wt% with two-stage electrodialysis (Vc:Vd=1:3); while the special energy demand could be as low as 30.9kWh/m3 in one-stage ED when the operate voltage was 4V. From the viewpoint of energy consumption, “a high volume ratio concentrating” with volume ratio of 1:10 was more competitive than “two-stage concentrating”. Naturally, electrodialysis is not only energy saving but also high-effective for lithium extraction and concentrating.
•ED was used to concentrate lithium salt from primary resource.•The highest mass fraction of Li2SO4 could reach 17.43wt%.•Multi-stage concentrating was competitive for Li2SO4 concentrating.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Myelodysplastic syndrome (MDS) is characterized by activated inflammatory signaling and affects prognosis. Targeting inflammatory signaling may provide a way to treat the disease. We were curious ...whether there were changes in A20 in peripheral blood mononuclear cells (PBMC) of MDS patients. Therefore, we conducted a study with 60 clinical samples, including 30 MDS patients and 30 healthy controls. All patients with MDS were diagnosed and classified according to the criteria of the 2016 World Health Organization. The study was performed in accordance with the guidelines of the Declaration of Helsinki. Using Quantitative Real-Time RT-PCR, we discovered that A20 mRNA expression in PBMC of the MDS group was significantly lower than that in the control group (
< 0.001). Additionally, using Luminex Liquid Suspension Chip, we observed elevated plasma levels of pro-inflammatory IL-8 and TNF-α in the MDS group compared to the healthy control group (
< 0.001). We did not find a significant correlation between A20 mRNA and clinical characteristics (age, sex, concentration of hemoglobin, neutrophils count, platelets count, percent of blasts, and WHO classification) of the patients, nor between A20 mRNA and plasma cytokines (data not shown). Our study found down-regulated of A20 and increased levels of pro-inflammatory cytokines in the peripheral blood of MDS patients, providing further evidence for the activation of inflammatory signals in MDS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Sevelamer hydrochloride is used widely, but its impact upon cardiovascular calcification, cardiovascular mortality, all-cause mortality and hospitalization is not known.
Primary outcome was ...cardiovascular calcification (coronary artery calcification scores (CACS) and aortic calcification scores (ACS)). Secondary outcomes were serum characteristics, hospitalization, cardiovascular mortality and all-cause mortality. Risk ratio (RR), mean differences and standard mean difference with 95% confidence intervals (CIs) were pooled using random- or fixed-effects models.
We identified 31 studies (on 23 randomized controlled trials with 4395 participants). An analysis pooling showed a significant decrease in serum levels of phosphate with calcium-based phosphate binders (CBPBs) by 0.17 mg/dL mean difference (MD), 95% CI, 0.03, 0.31 than sevelamer. A significant difference in the change of CACS by -102.66 MD: 95% CI, -159.51, -45.80 and ACS by -1008.73 MD, 95% CI, -1664.75, -352.72 between sevelamer and CBPBs was observed. Prevalence of hypercalcemia (serum levels of calcium >10.2-10.5 mg/dL and >11.0 mg/dL) was significantly smaller for sevelamer (RR = 0.44, 95% CI, 0.33, 0.58; RR = 0.24, 95% CI, 0.14, 0.40). No significant difference was found in hospitalization, all-cause mortality or cardiovascular mortality.
This meta-analysis suggests that sevelamer benefits dialysis patients in terms of CACS, ACS and hypercalcemia.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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