Noncoding RNAs play important roles in cancer biology, providing potential targets for cancer intervention. As a new class of endogenous noncoding RNAs, circular RNAs (circRNAs) have been recently ...identified in cell development and function, and certain types of pathological responses, generally acting as a microRNA (miRNA) sponge to regulate gene expression. Identifying the deregulated circRNAs and their roles in cancer has attracted much attention. However, the expression profile and function of circRNAs in human hepatocellular carcinoma (HCC) remain to be investigated. Here, we analyzed the expression profile of human circRNAs in HCC tissues and identified circMTO1 (mitochondrial translation optimization 1 homologue; hsa_circRNA_0007874/hsa_circRNA_104135) as one circRNA significantly down‐regulated in HCC tissues. HCC patients with low circMTO1 expression had shortened survival. By using a biotin‐labeled circMTO1 probe to perform RNA in vivo precipitation in HCC cells, we identified miR‐9 as the circMTO1‐associated miRNA. Furthermore, silencing of circMTO1 in HCC could down‐regulate p21, the target of oncogenic miR‐9, resulting in the promotion of HCC cell proliferation and invasion. In addition, the tumor‐promoting effect of circMTO1 silencing was blocked by miR9 inhibitor. Intratumoral administration of cholesterol‐conjugated circMTO1 small interfering RNA promoted tumor growth in HCC‐bearing mice in vivo. Conclusion: circMTO1 suppresses HCC progression by acting as the sponge of oncogenic miR‐9 to promote p21 expression, suggesting that circMTO1 is a potential target in HCC treatment. The decrease of circMTO1 in HCC tissues may serve as a prognosis predictor for poor survival of patients. (Hepatology 2017;66:1151‐1164).
The temperature sensitivity (Q10) of soil heterotrophic respiration (Rh) is an important ecological model parameter and may vary with temperature and moisture. While Q10 generally decreases with ...increasing temperature, the moisture effects on Q10 have been controversial. To address this, we conducted a 90-day laboratory incubation experiment using a subtropical forest soil with a full factorial combination of five moisture levels (20%, 40%, 60%, 80%, and 100% water holding capacity--WHC) and five temperature levels (10, 17, 24, 31, and 38°C). Under each moisture treatment, Rh was measured several times for each temperature treatment to derive Q10 based on the exponential relationships between Rh and temperature. Microbial biomass carbon (MBC), microbial community structure and soil nutrients were also measured several times to detect their potential contributions to the moisture-induced Q10 variation. We found that Q10 was significantly lower at lower moisture levels (60%, 40% and 20% WHC) than at higher moisture level (80% WHC) during the early stage of the incubation, but became significantly higher at 20%WHC than at 60% WHC and not significantly different from the other three moisture levels during the late stage of incubation. In contrast, soil Rh had the highest value at 60% WHC and the lowest at 20% WHC throughout the whole incubation period. Variations of Q10 were significantly associated with MBC during the early stages of incubation, but with the fungi-to-bacteria ratio during the later stages, suggesting that changes in microbial biomass and community structure are related to the moisture-induced Q10 changes. This study implies that global warming's impacts on soil CO2 emission may depend upon soil moisture conditions. With the same temperature rise, wetter soils may emit more CO2 into the atmosphere via heterotrophic respiration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hepatocellular carcinoma (HCC)-the most common form of liver cancer-is an aggressive malignancy with few effective treatment options
. Lenvatinib is a small-molecule inhibitor of multiple receptor ...tyrosine kinases that is used for the treatment of patients with advanced HCC, but this drug has only limited clinical benefit
. Here, using a kinome-centred CRISPR-Cas9 genetic screen, we show that inhibition of epidermal growth factor receptor (EGFR) is synthetic lethal with lenvatinib in liver cancer. The combination of the EGFR inhibitor gefitinib and lenvatinib displays potent anti-proliferative effects in vitro in liver cancer cell lines that express EGFR and in vivo in xenografted liver cancer cell lines, immunocompetent mouse models and patient-derived HCC tumours in mice. Mechanistically, inhibition of fibroblast growth factor receptor (FGFR) by lenvatinib treatment leads to feedback activation of the EGFR-PAK2-ERK5 signalling axis, which is blocked by EGFR inhibition. Treatment of 12 patients with advanced HCC who were unresponsive to lenvatinib treatment with the combination of lenvatinib plus gefitinib (trial identifier NCT04642547) resulted in meaningful clinical responses. The combination therapy identified here may represent a promising strategy for the approximately 50% of patients with advanced HCC who have high levels of EGFR.
Prophylactic transarterial chemoembolization (p-TACE) is frequently conducted for patients with hepatocellular carcinoma (HCC) in China, but the question of who could benefit from it remains ...controversial. Hence, we wanted to establish a nomogram model to identify patients eligible for p-TACE. Data from HCC patients receiving R0 resection with or without p-TACE between January 2013 and December 2014 were identified, using primary liver cancer big data, to establish a nomogram model to predict overall survival (OS). Based on the model, Patients receiving R0 resection between January 2015 and December 2015 were divided into three subgroups, and survival curves were constructed using the Kaplan-Meier method and analyzed by the log-rank test among patients in each subgroup. A nomogram integrating the neutrophil to lymphocyte ratio, AFP, tumor diameter, and microvascular invasion was developed to predict the OS of patients with HCC receiving R0 resection, and significant differences were observed in the median OS of the subgroups of low-risk (less than or equal to20), intermediate-risk (20~120), and high-risk (>120) identified by the current model. This model showed good calibration and discriminatory power in the validation cohort and the external cohort (c-index of 0.669 and 0.676, respectively). In the external cohort, the Kaplan-Meier curves showed that p-TACE could only significantly prolong the median OS of high-risk patients (25.6 vs. 33.7 months, P0.05). This readily available nomogram model could help guide decisions about p-TACE, but it needs further validation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An efficient serum marker for hepatocellular carcinoma (HCC) is currently lacking and requires intensive exploration. We aimed to evaluate the performance of des-gamma-carboxy prothrombin (DCP) for ...identifying hepatitis B virus-related HCC in a large, multicentre study in China. A total of 1034 subjects in three cohorts (A, B, and C) including HCC and various non-HCC controls were enrolled from 4 academic medical centers in China from January 2011 to February 2014. Blind parallel detections were conducted for DCP and AFP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacies. In cohort A, which comprised 521 subjects, including patients with HCC, liver metastasis, liver cirrhosis (LC), and liver hemangiomas as well as healthy controls (HCs), the accuracy of DCP for distinguishing HCC from various controls was 6.2-9.7% higher than that of AFP. In cohort B, which comprised 447 subjects, including patients with HCC, LC, and chronic hepatitis B as well as HC, the accuracy of DCP was further elevated (12.3-20.67% higher than that of AFP). The superiority of DCP to AFP was more profound in the surveillance of early HCC AUC 0.837 (95% CI: 0.771-0.903) vs. 0.650 (0.555-0.745) and AFP-negative HCC AUC: 0.856 (0.798-0.914) and in discriminating HCC from LC (accuracy: 92.9% vs.64.71%). Higher DCP levels were associated with worse clinical behaviors and shorter disease-free survival. DCP not only is complementary to AFP in identifying AFP-negative HCC and in excluding AFP-positive non-HCC (liver cirrhosis), but also demonstrates improved performance in HCC surveillance, early diagnosis, treatment response and recurrence monitoring in the HBV-related population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
With the depletion of fossil fuels and the increasing demand of energy for economic development, it is urgent to develop renewable energy technologies to sustain the economic growth. Electrospinning ...is a versatile and efficient fabrication method for one-dimensional (1D) nanostructured fibers of metals, metal oxides, hydrocarbons, composites, and so forth. The resulting nanofibers (NFs) with controllable diameters ranging from nanometer to micrometer scale possess unique properties such as a high surface-area-to-volume and aspect ratio, low density, and high pore volume. These properties make 1D nanomaterials more advantageous than conventional materials in energy harvesting, conversion, and storage devices. In this review, the key parameters for e-spinning are discussed and the properties of electrospun NFs and applications in solar cells, fuel cells, nanogenerators, hydrogen energy harvesting and storage, lithium-ion batteries, and supercapacitors are reviewed. The advantages and disadvantages of electrospinning and an outlook on the possible future directions are also discussed.
Samples of (110), (100), and (111) MgO single crystals were implanted with 70 keV N ions at room temperature. All as-implanted samples showed room temperature hysteresis in magnetization loops. The ...observed saturation magnetization (Ms) was 0.79 × 10−4 emu/g, 1.28 × 10−4 emu/g, and 1.5 × 10−4 emu/g for (110), (100) and (111) orientation implanted-MgO and follows the relation Ms(111) > Ms(100) > Ms(110), indicative of crystalline orientation-dependent ferromagnetism in N-implanted MgO. The samples were characterized by X-ray photoelectron spectroscopy (XPS), high resolution X-ray diffraction (HRXRD), reciprocal space mapping (RSM), and photoluminescence (PL). The results indicated that the amount of N-substitute-O and N-interstitial defects in these three N-implanted MgO samples showed the same changing tendency as compared with Ms data. Thus, we conclude that the N-substitute-O and N-interstitial defects may play a crucial role in controlling the N+-implanted-induced ferromagnetism.
The full scale of human miRNome in specific cell or tissue, especially in cancers, remains to be determined. An in-depth analysis of miRNomes in human normal liver, hepatitis liver, and ...hepatocellular carcinoma (HCC) was carried out in this study. We found nine miRNAs accounted for ∼88.2% of the miRNome in human liver. The third most highly expressed miR-199a/b-3p is consistently decreased in HCC, and its decrement significantly correlates with poor survival of HCC patients. Moreover, miR-199a/b-3p can target tumor-promoting PAK4 to suppress HCC growth through inhibiting PAK4/Raf/MEK/ERK pathway both in vitro and in vivo. Our study provides miRNomes of human liver and HCC and contributes to better understanding of the important deregulated miRNAs in HCC and liver diseases.
► Identification of miRNomes in human normal liver, hepatitis liver and HCC ► miR-199a/b-3p is the most consistently decreased miRNA in HCC ► Low miR-199-3p expression correlates with poor survival of HCC patients ► miR-199-3p inhibits PAK4/Raf/MEK/ERK prosurvival pathway in HCC
Abstract Background Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) is recommended before primary prevention implantable cardioverter-defibrillator ...(ICD) placement. Adherence to this recommendation and associated outcomes are unknown. Objectives This study examined the use of GDMT (≥1 prescription filled for both a renin-angiotensin inhibitor RAI and a heart failure–approved beta-blocker HFBB) within 90 days before primary prevention ICD placement in patients with HFrEF. Methods Data from the National Cardiovascular Data Registry ICD Registry were merged with a 40% random sample of Medicare administrative data. Prescription fills for recipients of primary prevention ICD between 2007 and 2011 were examined, analyzing GDMT overall and for each U.S. hospital referral region. We identified characteristics associated with GDMT and the association with 1-year mortality. Results Among 19,733 patients with HFrEF and primary prevention ICD, 61.1% filled any GDMT before implantation. Across hospital referral regions, GDMT was applied in 51% to 71%. The strongest predictors of any GDMT included absence of chronic renal disease or nonsustained ventricular tachycardia, low-income prescription benefits subsidy, and less recent left ventricular ejection fraction evaluation. Patients receiving GDMT versus those without had a lower 1-year mortality rate after ICD implantation (11.1% vs. 16.2%), even after adjustment for comorbidities, left ventricular ejection fraction, and functional heart failure class. Conclusions Rates of GDMT for HFrEF before primary prevention ICD implantation were low, and failure to achieve GDMT was associated with significantly decreased 1-year survival.
Identifying tumor-induced leukocyte subsets and their derived circulating factors has been instrumental in understanding cancer as a systemic disease. Nevertheless, how primary tumor-induced ...non-leukocyte populations in distal organs contribute to systemic spread remains poorly defined. Here, we report one population of tumor-inducible, erythroblast-like cells (Ter-cells) deriving from megakaryocyte-erythroid progenitor cells with a unique Ter-119+CD45−CD71+ phenotype. Ter-cells are enriched in the enlarged spleen of hosts bearing advanced tumors and facilitate tumor progression by secreting neurotrophic factor artemin into the blood. Transforming growth factor β (TGF-β) and Smad3 activation are important in Ter-cell generation. In vivo blockade of Ter-cell-derived artemin inhibits hepatocellular carcinoma (HCC) growth, and artemin deficiency abolishes Ter-cells’ tumor-promoting ability. We confirm the presence of splenic artemin-positive Ter-cells in human HCC patients and show that significantly elevated serum artemin correlates with poor prognosis. We propose that Ter-cells and the secreted artemin play important roles in cancer progression with prognostic and therapeutic implications.
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•Ter-119+CD45− erythroblast-like cells were induced in spleen of tumor-bearing mice•TGF-β and Smad3 activation are important in the generation of splenic Ter-cells•Splenic Ter-cells produce artemin, and high serum artemin predicts poor prognosis•Blockade of artemin or its receptor GFRα3 signaling inhibits tumor progression
A population of immune cells in the erythroid lineage are induced in a mouse model of hepatocellular carcinoma, which promotes tumor progression through artemin production.
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