Abstract
5-Methylcytosine (m5C) plays an extremely important role in the basic biochemical process. With the great increase of identified m5C sites in a wide variety of organisms, their epigenetic ...roles become largely unknown. Hence, accurate identification of m5C site is a key step in understanding its biological functions. Over the past several years, more attentions have been paid on the identification of m5C sites in multiple species. In this work, we firstly summarized the current progresses in computational prediction of m5C sites and then constructed a more powerful and reliable model for identifying m5C sites. To train the model, we collected experimentally confirmed m5C data from Homo sapiens, Mus musculus, Saccharomyces cerevisiae and Arabidopsis thaliana, and compared the performances of different feature extraction methods and classification algorithms for optimizing prediction model. Based on the optimal model, a novel predictor called iRNA-m5C was developed for the recognition of m5C sites. Finally, we critically evaluated the performance of iRNA-m5C and compared it with existing methods. The result showed that iRNA-m5C could produce the best prediction performance. We hope that this paper could provide a guide on the computational identification of m5C site and also anticipate that the proposed iRNA-m5C will become a powerful tool for large scale identification of m5C sites.
Helium (He) bubbles are typical radiation defects in structural materials in nuclear reactors after high dose energetic particle irradiation. In the past decades, extensive studies have been ...conducted to explore the dynamic evolution of He bubbles under various conditions and to investigate He-induced hardening and embrittlement. In this review, we summarize the current understanding of the behavior of He bubbles in metals; overview the mechanisms of He bubble nucleation, growth, and coarsening; introduce the latest methods of He control by using interfaces in nanocrystalline metals and metallic multilayers; analyze the effects of He bubbles on strength and ductility of metals; and point out some remaining questions related to He bubbles that are crucial for design of advanced radiation-tolerant materials.
This study explores the role of the long noncoding RNA (LncRNA) CRNDE in cisplatin (CDDP) resistance of gastric cancer (GC) cells. Here, we show that LncRNA CRNDE is upregulated in carcinoma tissues ...and tumor‐associated macrophages (TAMs) of GC patients. In vitro experiments show that CRNDE is enriched in M2‐polarized macrophage‐derived exosomes (M2‐exo) and is transferred from M2 macrophages to GC cells via exosomes. Silencing CRNDE in M2‐exo reverses the promotional effect of M2‐exo on cell proliferation in CDDP‐treated GC cells and homograft tumor growth in CDDP‐treated nude mice. Mechanistically, CRNDE facilitates neural precursor cell expressed developmentally downregulated protein 4‐1 (NEDD4‐1)‐mediated phosphatase and tensin homolog (PTEN) ubiquitination. Silencing CRNDE in M2‐exo enhances the CDDP sensitivity of GC cells treated with M2‐exo, which is reduced by PTEN knockdown. Collectively, these data reveal a vital role for CRNDE in CDDP resistance of GC cells and suggest that the upregulation of CRNDE in GC cells may be attributed to the transfer of TAM‐derived exosomes.
SYNOPSIS
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin.
LncRNA CRNDE is enriched in TAMs of GC patients.
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes in vitro.
CRNDE facilitates NEDD4‐1‐mediated PTEN ubiquitination in GC cells.
Exosomal transfer of LncRNA CRNDE is linked to cisplatin resistance in GC cells caused by reduced PTEN levels.
LncRNA CRNDE is transferred from M2‐polarized macrophages to GC cells via exosomes, suppressing PTEN expression in GC cells. The latter leads to a reduced sensitivity of GC cells to cisplatin.
Cancer stem cells are undifferentiated cancer cells that have self‐renewal ability, a high tumorigenic activity, and a multilineage differentiation potential. MicroRNAs play a critical role in ...regulating gene expression during carcinogenesis. Here, we investigated the role of miR‐7 and the mechanism by which it is dysregulated in gastric cancer stem cells (GCSCs). The stem cell marker, CD44, was used to sort GCSCs by fluorescence‐activated cell sorting. We found that CD44 (+) cells have higher invasiveness and form more number of sphere colonies than CD44 (−) cells. Quantitative real‐time polymerase chain reaction (PCR) revealed that the miR‐7‐5p expression was remarkably downregulated in GCSCs but was significantly increased in the methionine‐deprived medium. The downregulation of miR‐7‐5p results from the increased DNA methylation in the promoter region using the methylation‐specific PCR. Overexpression of miR‐7‐5p reduced the formation of colony and decreased the invasion of GCSCs through targeting Smo and Hes1 and subsequent repressing Notch and Hedgehog signaling pathways in vitro. Notably, upregulating miR‐7‐5p inhibited the growth of tumor in the xenograft model. Hence, these data demonstrated that miR‐7‐5p represses GCSC invasion through inhibition of Smo and Hes1, which provides a potential therapeutic target of gastric cancer treatment.
This paper mainly talks about the Cauchy two-matrix model and its corresponding integrable hierarchy with the help of orthogonal polynomial theory and Toda-type equations. Starting from the symmetric ...reduction in Cauchy biorthogonal polynomials, we derive the Toda equation of CKP type (or the C-Toda lattice) as well as its Lax pair by introducing time flows. Then, matrix integral solutions to the C-Toda lattice are extended to give solutions to the CKP hierarchy which reveals the time-dependent partition function of the Cauchy two-matrix model is nothing but the
τ
-function of the CKP hierarchy. At last, the connection between the Cauchy two-matrix model and Bures ensemble is established from the point of view of integrable systems.
Background
Autophagy plays an important role in regulating cisplatin (CDDP) resistance in gastric cancer cells. However, the underlying mechanism of methioninase (METase) in the regulation of ...autophagy and CDDP resistance of gastric cancer cells is still not clear.
Materials and methods
Western blot was used to detect the levels of autophagy-related proteins, multidrug-resistant 1 (MDR-1), and FoxM1 protein. LncRNA HULC was detected by qRT-PCR. Cell viability was detected using CCK-8 assay. The interaction between lncRNA HULC and FoxM1 was confirmed by RNA pull-down and RIP assay.
Results
Lentiviral vector carrying METase (LV-METase) suppressed autophagy and CDDP resistance of drug-resistant gastric cancer cells. LncRNA HULC was significantly downregulated in drug-resistant gastric cancer cells transfected with LV-METase. Besides, we found that lncRNA HULC interacted with FoxM1. In addition, METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1, and interfering HULC suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating FoxM1. Finally, interfering HULC inhibited tumor growth in vivo.
Conclusion
METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1 pathway.
Inspired by Okounkov's work (2001) 20 which relates KP hierarchy to determinant point process, we establish a relationship between BKP hierarchy and Pfaffian point process. We prove that the ...correlation function of the shifted Schur measures on strict partitions can be expressed as a Pfaffian of skew symmetric matrix kernel, whose elements are certain vacuum expectations of neutral fermions. We further show that the matrix integrals solution of BKP hierarchy can also induce a certain Pfaffian point process.
Background/Aims
Targeted drug delivery vehicles with low immunogenicity and toxicity are needed for cancer therapy. Here, we prepare an active targeting drug carrier of low immunogenicity and ...toxicity for targeted therapy.
Methods
Immature dendritic cells (imDCs) from BALB/c mice were used as donor cells of exosomes (Exos) that were transfected with the plasmids expressing fusion proteins of a tumor-targeting peptide known as internalizing RGD (iRGD) to construct a type of tumor-targeting iRGD-Exos and observe the interaction between these iRGD-Exos. Also, recombinant methioninase (rMETase) was loaded into the iRGD-Exos by electroporation to construct iRGD-Exos-rMETase and to assess the tumor-targeting function of the iRGD-Exos-rMETase. Finally, 30 BALB/c were randomly divided into five groups (
n
= 6), to observe tumor growth in vivo.
Results
The iRGD-Exos-rMETase was 99.58 nm in diameter and presented a unique “goblet” structure under transmission electron microscopy (TEM), with the encapsulation efficiency (EE) of 19.05%. iRGD-Exos-rMETase group has the strongest tumor suppressive effect. Compared to the iRGD-Exos-rMETase group, rMETase group and the blank-Exos-rMETase group were less effective, while the PBS group and the iRGD-Exos group showed no inhibitory effect on tumor growth. After treatment, the iRGD-Exos-rMETase group had gastric tumors significantly smaller and lighter than the other groups (
P
< 0.05).
Conclusion
The iRGD-Exos-rMETase is an effective antitumor therapy that delivers rMETase to tumor tissue using the iRGD-Exos. With its favorable inhibitory effect and tumor-targeting function, the iRGD-Exos-rMETase shows excellent potential value and exciting prospects in clinical applications.
Straw returning usually gives rise to greenhouse gas (GHG) emissions from the soil, and thus negatively affects carbon footprint (CF) of crop production. Numerous studies reported the effects of ...straw returning on the CF from single crop production. However, little is known about the integrated effects of different levels of straw returning on the CF and net ecosystem economic benefits (NEEB) from rice-wheat rotation. Here, we investigated the effects of different amounts of straw returning on soil CH
4
and N
2
O emissions, GHG emissions from agricultural inputs (AIGHG), CF, and NEEB from a 2-year cycle of rice-wheat rotation. The CF was determined based on the total GHG emissions associated with crop production inputs and services. Overall, straw returning significantly increased annual CH
4
emissions by 5.4–72.2% and reduced annual N
2
O emissions by 3.3–31.4% compared with straw removal. Straw returning remarkably increased rice grain yields by 8.1–9.9% and wheat grain yields by 10.2–21.1% compared with straw removal. The average annual AIGHG from rice-wheat rotation ranged from 3579 to 4987 kg CO
2
-eq ha
–1
. Diesel consumption played a dominant role in the AIGHG. The annual CF ranged from 0.96 to 1.31 kg CO
2
-eq kg
–1
and increased with increasing straw returning amounts. The NEEB, which ranged from 14161 to 17413 CNY ha
–1
, was significantly affected by the levels of straw returning. The treatment with returning of 1/3 of preceding crop straw to the field (2.19–2.47 kg ha
−1
year
−1
of rice straw in the wheat season and 1.38–1.68 kg ha
−1
year
−1
of wheat straw in the rice season) resulted in relatively higher grain yield, the lowest CF, and the highest NEEB among all treatments, and thus can reduce CF, and increase grain yields and NEEB, and thus can be recommended as a sustainable approach to mitigate GHG emissions and increase economic benefits from rice-wheat rotation.
The soluble carrier hormone binding protein (HBP) plays an important role in the growth of human and other animals. HBP can also selectively and non-covalently interact with hormone. Therefore, ...accurate identification of HBP is an important prerequisite for understanding its biological functions and molecular mechanisms. Since experimental methods are still labor intensive and cost ineffective to identify HBP, it's necessary to develop computational methods to accurately and efficiently identify HBP. In this paper, a machine learning-based method was proposed to identify HBP, in which the samples were encoded by using the optimal tripeptide composition obtained based on the binomial distribution method. In the 5-fold cross-validation test, the proposed method yielded an overall accuracy of 97.15%. For the convenience of scientific community, a user-friendly webserver called HBPred2.0 was built, which could be freely accessed at http://lin-group.cn/server/HBPred2.0/.
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