Derived from our original nomogram study by using the risk variables from multivariable analyses in the derivation cohort of 1383 patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL) who ...were mostly treated with anthracycline-based chemotherapy, we propose an easily used nomogram-revised risk index (NRI), validated it and compared with Ann Arbor staging, the International Prognostic Index (IPI), Korean Prognostic Index (KPI), and prognostic index of natural killer lymphoma (PINK) for overall survival (OS) prediction by examining calibration, discrimination, and decision curve analysis in a validation cohort of 1582 patients primarily treated with non-anthracycline-based chemotherapy. The calibration of the NRI showed satisfactory for predicting 3- and 5-year OS in the validation cohort. The Harrell's C-index and integrated Brier score (IBS) of the NRI for OS prediction demonstrated a better performance than that of the Ann Arbor staging system, IPI, KPI, and PINK. Decision curve analysis of the NRI also showed a superior outcome. The NRI is a promising tool for stratifying patients with ENKTCL into risk groups for designing clinical trials and for selecting appropriate individualized treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this paper, we use a robust inversion algorithm, which we have tested in many regional studies, to obtain the first global model of Curie-point depth (GCDM) from magnetic anomaly inversion based ...on fractal magnetization. Statistically, the oceanic Curie depth mean is smaller than the continental one, but continental Curie depths are almost bimodal, showing shallow Curie points in some old cratons. Oceanic Curie depths show modifications by hydrothermal circulations in young oceanic lithosphere and thermal perturbations in old oceanic lithosphere. Oceanic Curie depths also show strong dependence on the spreading rate along active spreading centers. Curie depths and heat flow are correlated, following optimal theoretical curves of average thermal conductivities K = ~2.0 W(m°C)
for the ocean and K = ~2.5 W(m°C)
for the continent. The calculated heat flow from Curie depths and large-interval gridding of measured heat flow all indicate that the global heat flow average is about 70.0 mW/m
, leading to a global heat loss ranging from ~34.6 to 36.6 TW.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
BACKGROUND:The adult mammalian cardiomyocytes lose their proliferative capacity, which is responsible for cardiac dysfunction and heart failure following injury. The molecular mechanisms underlying ...the attenuation of adult cardiomyocyte proliferation remain largely unknown. Because long noncoding RNAs (lncRNAs) have a critical role in the development of cardiovascular problems, we investigated whether lncRNAs have any role in the regulation of cardiomyocyte proliferation and cardiac repair.
METHODS:Using bioinformatics and initial analysis, we identified an lncRNA, named CPR (cardiomyocyte proliferation regulator), that has a potential regulatory role in cardiomyocyte proliferation. For in vivo experiments, we generated CPR knockout and cardiac-specific CPR-overexpressing mice. In isolated cardiomyocytes, we used adenovirus for silencing (CPR–small interfering RNA) or overexpressing CPR. To investigate the mechanisms of CPR function in cardiomyocyte proliferation, we performed various analyses including quantitative reverse transcription–polymerase chain reaction, Western blot, histology, cardiac function (by echocardiography), transcriptome analyses (microarray assay), RNA pull-down assay, and chromatin immunoprecipitation assay.
RESULTS:CPR level is comparatively higher in the adult heart than in the fetal stage. The silencing of CPR significantly increased cardiomyocyte proliferation in postnatal and adult hearts. Moreover, CPR deletion restored the heart function after myocardial injury, which was evident from increased cardiomyocyte proliferation, improvement of myocardial function, and reduced scar formation. In contrast, the neonatal cardiomyocyte proliferation and cardiac regeneration were remarkably suppressed in CPR-overexpressing mice or adeno-associated virus serotype 9–CPR—overexpressing heart. These results indicate that CPR acts as a negative regulator of cardiomyocyte proliferation and regeneration. Next, we found that CPR targets minichromosome maintenance 3, an initiator of DNA replication and cell cycle progression, to suppress cardiomyocyte proliferation. CPR silenced minichromosome maintenance 3 expression through directly interacting and recruiting DNMT3A to its promoter cysteine-phosphate-guanine sites, as evident from decreased minichromosome maintenance 3 promoter methylation and increased minichromosome maintenance 3 expression in CPR knocked-down cardiomyocytes and CPR knockout mouse heart. These results were confirmed in CPR-overexpressing cardiomyocytes and CPR-overexpressing mouse heart.
CONCLUSIONS:Together, our findings identified that CPR is a suppressor of cardiomyocyte proliferation and indicated that lncRNAs take part in the regulation of cardiomyocyte proliferation and cardiac repair. Our study provides an lncRNA-based therapeutic strategy for effective cardiac repair and regeneration.
Abstract
It is known that a trained restricted Boltzmann machine (RBM) on the binary Monte Carlo Ising spin configurations, generates a series of iterative reconstructed spin configurations which ...spontaneously flow and stabilize to the critical point of physical system. Here we construct a variety of neural network (NN) flows using the RBM and (variational) autoencoders, to study the
q
-state Potts and clock models on the square lattice for
q
= 2, 3, 4. The NN are trained on Monte Carlo spin configurations at various temperatures. We find that the trained NN flow does develop a stable point that coincides with critical point of the
q
-state spin models. The behavior of the NN flow is nontrivial and generative, since the training is unsupervised and without any prior knowledge about the critical point and the Hamiltonian of the underlying spin model. Moreover, we find that the convergence of the flow is independent of the types of NNs and spin models, hinting a universal behavior. Our results strengthen the potential applicability of the notion of the NN flow in studying various states of matter and offer additional evidence on the connection with the renormalization group flow.
Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the ...SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A new kind of high‐performance asymmetric supercapacitor is designed with pyrolyzed bacterial cellulose (p‐BC)‐coated MnO2 as a positive electrode material and nitrogen‐doped p‐BC as a negative ...electrode material via an easy, efficient, large‐scale, and green fabrication approach. The optimal asymmetric device possesses an excellent supercapacitive behavior with quite high energy and power density.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Glioma is the most aggressive primary brain tumor and is notorious for resistance to chemoradiotherapy. Although its associated mechanisms are still not completely understood, Notch signaling, an ...evolutionarily conserved pathway, appears to be the key processes involved. Nevertheless, its mechanisms are sophisticated, due to a variety of targets and signal pathways, especially microRNA. MicroRNAs, which are small noncoding regulatory RNA molecules, have been proposed as one of the key mechanisms in glioma pathogenesis. Among the known glioma associated microRNA, microRNA‐129, microRNA‐34 family, and microRNA‐326 have been shown to influence the progress of glioma through Notch signaling. Evidence also indicates that recurrence is due to development or persistence of the glioma stem‐like cells and active angiogenesis, which are tightly regulated by a variety of factors, including Notch signaling. In this review, we summarize the recent progress regarding the functional roles of Notch signaling in glioma, including Notch ligand, microRNA, intracellular crosstalk, glioma stem‐like cells and active angiogenesis and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for glioma.
Notch signaling and its ligands act as an oncogene in glioma; microRNAs influence the progress of glioma through Notch signaling; a combination of chemoradiotherapy and disruption of Notch signaling might be a new method of glioma therapy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We perform decoy-state quantum key distribution between a low-Earth-orbit satellite and multiple ground stations located in Xinglong, Nanshan, and Graz, which establish satellite-to-ground secure ...keys with ∼kHz rate per passage of the satellite Micius over a ground station. The satellite thus establishes a secure key between itself and, say, Xinglong, and another key between itself and, say, Graz. Then, upon request from the ground command, Micius acts as a trusted relay. It performs bitwise exclusive or operations between the two keys and relays the result to one of the ground stations. That way, a secret key is created between China and Europe at locations separated by 7600 km on Earth. These keys are then used for intercontinental quantum-secured communication. This was, on the one hand, the transmission of images in a one-time pad configuration from China to Austria as well as from Austria to China. Also, a video conference was performed between the Austrian Academy of Sciences and the Chinese Academy of Sciences, which also included a 280 km optical ground connection between Xinglong and Beijing. Our work clearly confirms the Micius satellite as a robust platform for quantum key distribution with different ground stations on Earth, and points towards an efficient solution for an ultralong-distance global quantum network.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
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