Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation and are associated with the development of cancers. To investigate the important role and mechanism of lncRNAs in the ...progression of gastric cancer, we screened lncRNAs in gastric cancer tissues and corresponding adjacent tissues, and assessed the effects on gastric cancer. Here, we report that BC032469, a novel lncRNA, expressed highly in gastric cancer tissues, and the upregulation was clinically associated with larger tumor size, poor differentiation and shorter survival of gastric cancer patients. Downregulation of BC032469 resulted in a significant inhibition of proliferation in vitro and in vivo. Mechanistically, BC032469 could directly bind to miR-1207-5p and effectively functioned as a sponge for miR-1207-5p to modulate the derepression of hTERT. Thus, BC032469 may function as a ceRNA to impair miR-1207-5p-dependent hTERT downregulation, suggesting that it may be clinically valuable as a poor prognostic biomarker of gastric cancer.
Abstract Induced pluripotent stem cells (iPSCs) hold great promise as a cell source for regenerative medicine yet its culture, maintenance of pluripotency and induction of differentiation remain ...challenging. Conversely, graphene (G) and graphene oxide (GO) have captured tremendous interests in the fields of materials science, physics, chemistry and nanotechnology. Here we report on that G and GO can support the mouse iPSCs culture and allow for spontaneous differentiation. Intriguingly, G and GO surfaces led to distinct cell proliferation and differentiation characteristics. In comparison with the glass surface, iPSCs cultured on the G surface exhibited similar degrees of cell adhesion and proliferation while iPSCs on the GO surface adhered and proliferated at a faster rate. Moreover, G favorably maintained the iPSCs in the undifferentiated state while GO expedited the differentiation. The iPSCs cultured on both G and GO surfaces spontaneously differentiated into ectodermal and mesodermal lineages without significant disparity, but G suppressed the iPSCs differentiation towards the endodermal lineage whereas GO augmented the endodermal differentiation. These data collectively demonstrated that the different surface properties of G and GO governed the iPSCs behavior and implicate the potentials of graphene-based materials as a platform for iPSCs culture and diverse applications.
Autotrophic nitrogen removal in the main stream appears as a prerequisite for the implementation of energy autarchic wastewater treatment plants. To investigate autotrophic nitrogen removal a ...lab-scale gas-lift sequencing batch reactor with granular sludge was operated for more than 500 days. The reactor was operated at temperatures between 20 and 10 °C on autotrophic medium with ammonium (60 and 160 mg-N L−1) as only nitrogen compound at an HRT of 0.23–0.3 d. The dissolved oxygen (DO) concentration was shown to be an effective control parameter for the suppression of the undesired nitratation process. DO control guaranteed the effective suppression of the nitratation both at 20 and 15 °C, allowing nitrogen removal rates of 0.4 g-NTot L−1 d−1 at nitrogen removal efficiencies of 85-75%. Prolonged operation at 10 °C caused a slow but unrestrainable decrease in anammox activity and process efficiency. This study represents a proof of concept for the application of the autotrophic nitrogen removal in a single reactor with granular sludge at main stream conditions.
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•Proof of concept: autotrophic N-removal with granules at main stream conditions.•Effective suppression of nitratation at DO up to 2.5 mg-O2 L−1 with NOB presence.•Nitrogen removal rates of 0.4 g-NTot L−1 d−1 with high removal efficiencies.•Decreased anammox activity and process efficiency after prolonged operation at 10 °C.
We report a measurement of electron antineutrino oscillation from the Daya Bay Reactor Neutrino Experiment with nearly 4 million reactor νover ¯_{e} inverse β decay candidates observed over 1958 days ...of data collection. The installation of a flash analog-to-digital converter readout system and a special calibration campaign using different source enclosures reduce uncertainties in the absolute energy calibration to less than 0.5% for visible energies larger than 2 MeV. The uncertainty in the cosmogenic ^{9}Li and ^{8}He background is reduced from 45% to 30% in the near detectors. A detailed investigation of the spent nuclear fuel history improves its uncertainty from 100% to 30%. Analysis of the relative νover ¯_{e} rates and energy spectra among detectors yields sin^{2}2θ_{13}=0.0856±0.0029 and Δm_{32}^{2}=(2.471_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the normal hierarchy, and Δm_{32}^{2}=-(2.575_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the inverted hierarchy.
Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small-cell lung cancer (NSCLC). The aim of our study was to determine prognostic risk factors and establish a novel nomogram ...for lung adenocarcinoma patients. Methods: This retrospective cohort study is based on the Surveillance, Epidemiology, and End Results (SEER) database and the Chinese multicenter lung cancer database. We selected 22,368 eligible LUAD patients diagnosed between 2010 and 2015 from the SEER database and screened them based on the inclusion and exclusion criteria. Subsequently, the patients were randomly divided into the training cohort (n = 15,657) and the testing cohort (n = 6711), with a ratio of 7:3. Meanwhile, 736 eligible LUAD patients from the Chinese multicenter lung cancer database diagnosed between 2011 and 2021 were considered as the validation cohort. Results: We established a nomogram based on each independent prognostic factor analysis for 1-, 3-, and 5-year overall survival (OS) . For the training cohort, the area under the curves (AUCs) for predicting the 1-, 3-, and 5-year OS were 0.806, 0.856, and 0.886. For the testing cohort, AUCs for predicting the 1-, 3-, and 5-year OS were 0.804, 0.849, and 0.873. For the validation cohort, AUCs for predicting the 1-, 3-, and 5-year OS were 0.86, 0.874, and 0.861. The calibration curves were observed to be closer to the ideal 45° dotted line with regard to 1-, 3-, and 5-year OS in the training cohort, the testing cohort, and the validation cohort. The decision curve analysis (DCA) plots indicated that the established nomogram had greater net benefits in comparison with the Tumor-Node-Metastasis (TNM) staging system for predicting 1-, 3-, and 5-year OS of lung adenocarcinoma patients. The Kaplan–Meier curves indicated that patients’ survival in the low-risk group was better than that in the high-risk group (P < .001). Conclusion: The nomogram performed very well with excellent predictive ability in both the US population and the Chinese population.
Atrial fibrillation (AF) is the most common clinical tachyarrhythmia with a strong tendency to progress in time. AF progression is driven by derailment of protein homeostasis, which ultimately causes ...contractile dysfunction of the atria. Here we report that tachypacing-induced functional loss of atrial cardiomyocytes is precipitated by excessive poly(ADP)-ribose polymerase 1 (PARP1) activation in response to oxidative DNA damage. PARP1-mediated synthesis of ADP-ribose chains in turn depletes nicotinamide adenine dinucleotide (NAD
), induces further DNA damage and contractile dysfunction. Accordingly, NAD
replenishment or PARP1 depletion precludes functional loss. Moreover, inhibition of PARP1 protects against tachypacing-induced NAD
depletion, oxidative stress, DNA damage and contractile dysfunction in atrial cardiomyocytes and Drosophila. Consistently, cardiomyocytes of persistent AF patients show significant DNA damage, which correlates with PARP1 activity. The findings uncover a mechanism by which tachypacing impairs cardiomyocyte function and implicates PARP1 as a possible therapeutic target that may preserve cardiomyocyte function in clinical AF.
Nitric oxide (NO) has important functions in biology and atmospheric chemistry as a toxin, signaling molecule, ozone depleting agent and the precursor of the greenhouse gas nitrous oxide (N
O). ...Although NO is a potent oxidant, and was available on Earth earlier than oxygen, it is unclear whether NO can be used by microorganisms for growth. Anaerobic ammonium-oxidizing (anammox) bacteria couple nitrite reduction to ammonium oxidation with NO and hydrazine as intermediates, and produce N
and nitrate. Here, we show that the anammox bacterium Kuenenia stuttgartiensis is able to grow in the absence of nitrite by coupling ammonium oxidation to NO reduction, and produce only N
. Under these growth conditions, the transcription of proteins necessary for NO generation is downregulated. Our work has potential implications in the control of N
O and NO emissions from natural and manmade ecosystems, where anammox bacteria contribute significantly to N
release to the atmosphere. We hypothesize that microbial NO-dependent ammonium oxidation may have existed on early Earth.
To assess the association between the elevation of plasma homocysteine (Hcy) level and long‐term levodopa (L‐dopa) therapy in idiopathic Parkinson's disease (PD). We performed a systematic literature ...review to recruit original studies published up to May 14, 2012. Studies enrolled should be controlled, with specific information of long‐term L‐dopa application and plasma Hcy in patients with PD. Effects were summarized using standardized mean differences (SMDs) or weighted mean differences (WMDs). Our search enrolled 22 eligible studies. Plasma Hcy levels were significantly higher in L‐dopa‐treated patients than those in healthy controls SMD 0.97; 95% confidence interval (CI) 0.80–1.14, P < 0.001, L‐dopa‐naïve patients with PD (SMD 0.99; 95% CI 0.54–1.44, P < 0.001), and untreated patients (SMD 0.52; 95% CI 0.18–0.86, P < 0.01). However, its levels in untreated patients with PD were not significantly higher than in healthy controls (SMD 0.24; 95% CI −0.03 to 0.51, P > 0.05). Patients with PD treated with L‐dopa plus catechol‐O‐methyltransferase inhibitor (COMT‐I) showed lower plasma Hcy concentrations compared with L‐dopa‐treated patients (WMD 4.62; 95% CI 2.89–6.35, P < 0.001). L‐dopa treatment is associated with the increase in plasma Hcy level in patients with PD. COMT‐I may attenuate L‐dopa‐induced elevation of Hcy level.
TP53 mutations are associated with the lowest survival rates in acute myeloid leukemia (AML). In addition to mutations, loss of p53 function can arise via aberrant expression of proteins that ...regulate p53 stability and function. We examined a large AML cohort using proteomics, mutational profiling and network analyses, and showed that (1) p53 stabilization is universal in mutant TP53 samples, it is frequent in samples with wild-type TP53, and in both cases portends an equally dismal prognosis; (2) the p53 negative regulator Mdm2 is frequently overexpressed in samples retaining wild-type TP53 alleles, coupled with absence of p21 expression and dismal prognosis similar to that of cases with p53 stabilization; (3) AML samples display unique patterns of p53 pathway protein expression, which segregate prognostic groups with distinct cure rates; (4) such patterns of protein activation unveil potential AML vulnerabilities that can be therapeutically exploited.
A measurement of electron antineutrino oscillation by the Daya Bay Reactor Neutrino Experiment is described in detail. Six 2.9-GWth nuclear power reactors of the Daya Bay and Ling Ao nuclear power ...facilities served as intense sources of ν¯e’s. Comparison of the ν¯e rate and energy spectrum measured by antineutrino detectors far from the nuclear reactors (∼1500–1950 m) relative to detectors near the reactors (∼350–600 m) allowed a precise measurement of ν¯e disappearance. More than 2.5 million ν¯e inverse beta-decay interactions were observed, based on the combination of 217 days of operation of six antineutrino detectors (December, 2011–July, 2012) with a subsequent 1013 days using the complete configuration of eight detectors (October, 2012–July, 2015). The ν¯e rate observed at the far detectors relative to the near detectors showed a significant deficit, R=0.949±0.002(stat)±0.002(syst). The energy dependence of ν¯e disappearance showed the distinct variation predicted by neutrino oscillation. Analysis using an approximation for the three-flavor oscillation probability yielded the flavor-mixing angle sin22θ13=0.0841±0.0027(stat)±0.0019(syst) and the effective neutrino mass-squared difference of |Δmee2|=(2.50±0.06(stat)±0.06(syst))×10−3 eV2. Analysis using the exact three-flavor probability found Δm322=(2.45±0.06(stat)±0.06(syst))×10−3 eV2 assuming the normal neutrino mass hierarchy and Δm322=(−2.56±0.06(stat)±0.06(syst))×10−3 eV2 for the inverted hierarchy.
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