Background and Aims
Trimethylation of Lys36 on histone 3 (H3K36me3) catalyzed by histone methyltransferase SET domain‐containing 2 (SETD2) is one of the most conserved epigenetic marks from yeast to ...mammals. SETD2 is frequently mutated in multiple cancers and acts as a tumor suppressor.
Approach and Results
Here, using a liver‐specific Setd2 depletion model, we found that Setd2 deficiency is sufficient to trigger spontaneous HCC. Meanwhile, Setd2 depletion significantly increased tumor and tumor size of a diethylnitrosamine‐induced HCC model. The mechanistic study showed that Setd2 suppresses HCC not only through modulating DNA damage response, but also by regulating lipid metabolism in the liver. Setd2 deficiency down‐regulated H3K36me3 enrichment and expression of cholesterol efflux genes and caused lipid accumulation. High‐fat diet enhanced lipid accumulation and promoted the development of HCC in Setd2‐deficient mice. Chromatin immunoprecipitation sequencing analysis further revealed that Setd2 depletion induced c‐Jun/activator protein 1 (AP‐1) activation in the liver, which was trigged by accumulated lipid. c‐Jun acts as an oncogene in HCC and functions through inhibiting p53 in Setd2‐deficient cells.
Conclusions
We revealed the roles of Setd2 in HCC and the underlying mechanisms in regulating cholesterol homeostasis and c‐Jun/AP‐1 signaling.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The motivation of this paper is to solve the problem of tourism majors' lack of theoretical knowledge and professional ability by building a capacity training mechanism model based on grounded ...theory. The goal of the study is to optimize the ability training strategies of tourism undergraduates and improve their professional quality and competitiveness. The paper adopts the ability training model based on grounded theory, and combines with Back Propagation (BP) neural network for optimization and evaluation. By comparing the performance of different ability training mechanisms, this paper explores the best training strategies to provide support and guidance for the training of tourism undergraduates. Firstly, the employment background of the current market is studied and analyzed. By sorting out the relevant documents of grounded theory and combining with the current training strategies of tourism majors, the students' personality characteristics and the basic principles of establishing models are integrated. The Back Propagation (BP) neural network is combined with the grounded theory. The data input of the student ability model is re-optimized. The undergraduate competency training mechanism model is constructed. The results show that when the number of iterations of the network model is 500.00, the evaluation accuracy of the competency training model based on BP neural network can reach 70.00%. At this time, the evaluation accuracy of competency training model based on content analysis method is only 55.00%. In addition, the results show that with the increase of model iterations, the recognition accuracy of the ability model based on grounded theory and the ability training mechanism of content analysis method is continuously improved. However, the ability evaluation model based on grounded theory has higher accuracy, and the accuracy of ability evaluation even exceeds 78.52% when the number of iterations of the network model is 600. Secondly, through the statistics and comparison of the grading results of students of different majors, it is found that the ability training mechanism based on grounded theory can improve the overall ability level of students more significantly. The research has important reference value for promoting the optimization and perfection of students' training strategies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report here the first example of ZIF materials synthesized in aqueous solution. The synthesis was performed at room temperature and typically took several minutes compared to hours and days in ...non-aqueous conditions. The obtained product were ZIF-8 nanocrystals having size of ~85 nm and showed excellent thermal, hydrothermal and solvothermal stabilities.
Differentiation of mesenchymal stem cells into a particular lineage is tightly regulated, and malfunction of this regulation could lead to pathological consequences. Patients with osteoporosis have ...increased adipocyte accumulation, but the mechanisms involved remain to be defined. In this study, we aimed to investigate if microRNAs regulate mesenchymal progenitor cells and bone marrow stromal cell (BMSC) differentiation through modulation of Runx2, a key transcription factor for osteogenesis. We found that miR‐204 and its homolog miR‐211 were expressed in mesenchymal progenitor cell lines and BMSCs and their expression was induced during adipocyte differentiation, whereas Runx2 protein expression was suppressed. Retroviral overexpression of miR‐204 or transfection of miR‐204 oligo decreased Runx2 protein levels and miR‐204 inhibition significantly elevated Runx2 protein levels, suggesting that miR‐204 acts as an endogenous attenuator of Runx2 in mesenchymal progenitor cells and BMSCs. Mutations of putative miR‐204 binding sites upregulated the Runx2 3′‐UTR reporter activity, suggesting that miR‐204/211 bind to Runx2 3′‐UTR. Perturbation of miR‐204 resulted in altered differentiation fate of mesenchymal progenitor cells and BMSCs: osteoblast differentiation was inhibited and adipocyte differentiation was promoted when miR‐204 was overexpressed in these cells, whereasosteogenesis was upregulated and adipocyte formation was impaired when miR‐204 was inhibited. Together, our data demonstrated that miR‐204/211 act as important endogenous negative regulators of Runx2, which inhibit osteogenesis and promote adipogenesis of mesenchymal progenitor cells and BMSCs. STEM CELLS 2010;28:357–364
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer related death in the world with a five-year survival rate of less than 5%. Not all PDAC are the same, because there exist ...intra-tumoral heterogeneity between PDAC, which poses a great challenge to personalized treatments for PDAC.
To dissect the molecular heterogeneity of PDAC, we performed a retrospective meta-analysis on whole transcriptome data from more than 1200 PDAC patients. Subtypes were identified based on non-negative matrix factorization (NMF) biclustering method. We used the gene set enrichment analysis (GSEA) and survival analysis to conduct the molecular and clinical characterization of the identified subtypes, respectively.
Six molecular and clinical distinct subtypes of PDAC: L1-L6, are identified and grouped into tumor-specific (L1, L2 and L6) and stroma-specific subtypes (L3, L4 and L5). For tumor-specific subtypes, L1 (~ 22%) has enriched carbohydrate metabolism-related gene sets and has intermediate survival. L2 (~ 22%) has the worst clinical outcomes, and is enriched for cell proliferation-related gene sets. About 23% patients can be classified into L6, which leads to intermediate survival and is enriched for lipid and protein metabolism-related gene sets. Stroma-specific subtypes may contain high non-epithelial contents such as collagen, immune and islet cells, respectively. For instance, L3 (~ 12%) has poor survival and is enriched for collagen-associated gene sets. L4 (~ 14%) is enriched for various immune-related gene sets and has relatively good survival. And L5 (~ 7%) has good clinical outcomes and is enriched for neurotransmitter and insulin secretion related gene sets. In the meantime, we identified 160 subtype-specific markers and built a deep learning-based classifier for PDAC. We also applied our classification system on validation datasets and observed much similar molecular and clinical characteristics between subtypes.
Our study is the largest cohort of PDAC gene expression profiles investigated so far, which greatly increased the statistical power and provided more robust results. We identified six molecular and clinical distinct subtypes to describe a more complete picture of the PDAC heterogeneity. The 160 subtype-specific markers and a deep learning based classification system may be used to better stratify PDAC patients for personalized treatments.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anthocyanins, which have important biological functions and have a beneficial effect on human health, notably account for pigmentation in purple-fleshed sweet potato tuberous roots. Individual ...regulatory factors of anthocyanin biosynthesis have been identified; however, the regulatory network of anthocyanin biosynthesis in purple-fleshed sweet potato is unclear.
We functionally determined that IbMYB340 cotransformed with IbbHLH2 in tobacco and strawberry receptacles induced anthocyanin accumulation, and the addition of IbNAC56a or IbNAC56b caused increased pigmentation. Furthermore, we confirmed the interaction of IbMYB340 with IbbHLH2 and IbNAC56a or IbNAC56b via yeast two-hybrid and firefly luciferase complementation assays; these proteins could form a MYB340-bHLH2-NAC56a or MYB340-bHLH2-NAC56b transcriptional complex to regulate anthocyanin biosynthesis by binding to the IbANS promoter rather than the IbUFGT promoter. Furthermore, it was found by a transient expression system in tobacco leaves that IbMYB44 could decrease anthocyanin accumulation. Moreover, the interaction of IbMYB44 with IbMYB340 and IbNAC56a or IbNAC56b was verified. This result suggested that IbMYB44 acts as a repressor of anthocyanin in sweet potato.
The repressor IbMYB44 affected anthocyanin biosynthesis by competitively inhibiting the IbMYB340-IbbHLH2-IbNAC56a or IbMYB340-IbbHLH2-IbNAC56b regulatory complex formation. Overall, the present study proposed a novel regulatory network whereby several vital TFs play key roles in regulating anthocyanin biosynthesis, and it provides strong insight into the potential mechanism underlying anthocyanin biosynthesis in sweet potato tuberous roots with purple color.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It was previously believed that obesity and osteoporosis were two unrelated diseases, but recent studies have shown that both diseases share several common genetic and environmental factors. Body fat ...mass, a component of body weight, is one of the most important indices of obesity, and a substantial body of evidence indicates that fat mass may have beneficial effects on bone. Contrasting studies, however, suggest that excessive fat mass may not protect against osteoporosis or osteoporotic fracture. Differences in experimental design, sample structure, and even the selection of covariates may account for some of these inconsistent or contradictory results. Despite the lack of a clear consensus regarding the impact of effects of fat on bone, a number of mechanistic explanations have been proposed to support the observed epidemiologic and physiologic associations between fat and bone. The common precursor stem cell that leads to the differentiation of both adipocytes and osteoblasts, as well the secretion of adipocyte‐derived hormones that affect bone development, may partially explain these associations. Based on our current state of knowledge, it is unclear whether fat has beneficial effects on bone. We anticipate that this will be an active and fruitful focus of research in the coming years.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A novel filtering power divider with wide stopband is presented in this letter. It utilizes four coupled quarter-wavelength resonators to obtain dual functions. Discriminating coupling is applied to ...the input and output feed lines and resonators, which not only to provide suitable coupling strength but also to suppress 3f 0 and 5f 0 (f 0 is the operating frequency). A resistor is connected at the two open-ends of the input feed line to obtain high isolation. Transmission zeros are generated near the passband edges, resulting in high selectivity. For demonstration, a power divider with filtering function as well as wide stopband is implemented. Good agreement between the prediction and measurement validates the proposed method.
Sepsis-associated encephalopathy (SAE) increases the mortality of septic patients, but its mechanism remains unclear. The present study aimed to investigate the roles of T lymphocytes, proBDNF, and ...their interaction in the pathogenesis of SAE.
Fear conditioning tests were conducted for cognitive assessment in the lipopolysaccharide (LPS, 5 mg kg
)-induced septic mice. Meninges and peripheral blood were harvested for flow cytometry or qPCR. FTY720 and monoclonal anti-proBDNF antibody (McAb-proB) were used to investigate the effect of lymphocyte depletion and blocking proBDNF on the impaired cognitive functions in the septic mice.
In the septic mice, cognitive function was impaired, the percentage of CD4
T cells were decreased in the meninges (P = 0.0021) and circulation (P = 0.0222), and pro-inflammatory cytokines were upregulated, but the anti-inflammatory cytokines interleukin (IL)-4 (P < 0.0001) and IL-13 (P = 0.0350) were downregulated in the meninges. Lymphocyte depletion by intragastrically treated FTY720 (1 mg kg
) for 1 week ameliorated LPS-induced learning deficit. In addition, proBDNF was increased in the meningeal (P = 0.0042) and peripheral (P = 0.0090) CD4
T cells. Intraperitoneal injection of McAb-proB (100 μg) before LPS treatment significantly alleviated cognitive dysfunction, inhibited the downregulation of meningeal (P = 0.0264) and peripheral (P = 0.0080) CD4
T cells, and normalized the gene expression of cytokines in the meninges. However, intra-cerebroventricular McAb-proB injection (1 μg) did not have such effect. Finally, exogenous proBDNF downregulated the percentage of CD4
T cells in cultured splenocytes from septic mice (P = 0.0021).
Upregulated proBDNF in immune system promoted the pathogenesis of SAE through downregulating the circulating CD4
T cells, limiting its infiltration into the meninges and perturbing the meningeal pro-/anti-inflammatory homeostasis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The potential impact of six antibiotics (chlortetracycline, tetracycline and tylosin; sulfamethoxazole, sulfamethazine and trimethoprim) on plant growth and soil quality was studied by using seed ...germination test on filter paper and plant growth test in soil, soil respiration and phosphatase activity tests. The phytotoxic effects varied between the antibiotics and between plant species (sweet oat, rice and cucumber). Rice was most sensitive to sulfamethoxazole with the EC10 value of 0.1
mg/L. The antibiotics tested inhibited soil phosphatase activity during the 22 days' incubation. Significant effects on soil respiration were found for the two sulfonamides (sulfamethoxazole and sulfamethazine) and trimethoprim, whereas little effects were observed for the two tetracyclines and tylosin. The effective concentrations (EC10 values) for soil respiration in the first 2 days were 7
mg/kg for sulfamethoxazole, 13
mg/kg for sulfamethazine and 20
mg/kg for trimethoprim. Antibiotic residues in manure and soils may affect soil microbial and enzyme activities.
Terrestrial ecotoxicological effects of antibiotics are related to their sorption and degradation behavior in soil.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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