Explore the vast range of titles available.

N6-methyladenosine (m 6 A) RNA methylation is profoundly involved in epigenetic regulation, especially for carcinogenesis and tumor progression. Mounting evidence suggests that methyltransferase METTL3 regulates malignant behaviors of gastric cancer (GC). However, the clinical significance and biological implication of SPHK2 and its related m 6 A modification in GC remain unclear. In this study, quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry were utilized to detect the expression profiles and prognostic significance of SPHK2 in GC. Here, we showed that increased SPHK2 was signified a poor prognosis of GC patients. Phosphorylation and ubiquitination assays were used to investigate the possible mechanisms of SPHK2-mediated KLF2 expression. SPHK2 can promote the phosphorylation of KLF2, which triggers the ubiquitination and degradation of KLF2 protein in GC. Methylated RNA immunoprecipitation (MeRIP) was performed to uncover the m 6 A modification of SPHK2 mRNA. METTL3 promotes translation of SPHK2 mRNA via an m 6 A-YTHDF1-dependent manner. Functionally, SPHK2 facilitates GC cell proliferation, migration and invasion by inhibiting KLF2 expression. SPHK2/KLF2 regulates the cell proliferation, migration, and invasion induced by METTL3 in GC. Overall, our findings reveal that METTL3-mediated m 6 A modification of SPHK2 contributes to GC progression, which extends the understanding of the importance m 6 A methylation in GC and represents a potential target for GC therapy.

SummaryThe insulin-like growth factor-2 mRNA-binding proteins (IGF2BPs) pertain to a highly conservative RNA-binding family that works as a post-transcriptional fine-tuner for target transcripts. Emerging evidence suggests that IGF2BPs regulate RNA processing and metabolism, including stability, translation, and localization, and are involved in various cellular functions and pathophysiologies. In this review, we summarize the roles and molecular mechanisms of IGF2BPs in cancer development and progression. We mainly discuss the functional relevance of IGF2BPs in embryo development, neurogenesis, metabolism, RNA processing, and tumorigenesis. Understanding IGF2BPs role in tumor progression will provide new insight into cancer pathophysiology.

Water shortages have become a major problem facing the world today. Membrane separation technology is commonly used in water treatment applications. The development of new materials for water treatment can reduce the energy required for water treatment, reduce cost, and improve efficiency. The unique structure and properties of graphene and silica make them attractive materials for preparation of nanofiltration membranes for water treatment. We have successfully prepared a graphene oxide/silica (GO/SiO2) hybrid composite materials by in situ hydrolysis, using tetraethyl orthosilicate (TEOS) as a silicon source in an alkaline environment. The chemistry and structure of these materials are characterized by TEM, FTIR, Raman, and XPS of GO and the GO/SiO2 composite. BET porosimetry reveals that the total pore volume of the composite is 2.84 cm3 g−1, the specific surface area is 2897 m2 g−1, and the average pore diameter is 3.97 nm. We prepared GO membranes and GO/SiO2 composite membranes by vacuum suction filtration. The morphology of the membrane was observed by FESEM and AFM. The composite membrane has a larger surface roughness (Rms = 9.39). We also tested the thermal stability by TGA, and hydrophilicity by water contact angle measurements. The water permeance of the composite membrane is up to 229.15 L m−2 h−1 bar−1, and the rejection of the rhodamine B dye molecules is as high as 99%. The GO/SiO2 hybrid composite membrane has good hydrophilicity and thermal stability, high water permeance and rejection, and can be developed as a high-performance material for water treatment.

In this study, the problem of the robust control of interconnected systems was investigated. A controller design method based on a state observer is proposed for nonlinear discrete interconnected systems with disturbance terms. In the proposed method, the observer and controller of the interconnected systems are designed separately, and sufficient conditions for the existence of the gain matrix are provided. In the design of the state observer, considering the convergence rate of the observation error, the performance of the state observer was improved by adding constraints. The influence of the external disturbance of the system on the state estimation is reduced by introducing a performance index, which provides the necessary theoretical basis for the design of the controller. In the controller design, based on the disk stability lemma and control theory, sufficient conditions for the existence of the controller are provided, and robust stabilization of the feedback closed-loop system was realized. In this study, the separate design method of the controller was compared with the centralized design method, which demonstrated the superiority of the separate design of the observer and controller. Finally, a numerical example is discussed, in which the separation design method of the robust controller was tested, and the effectiveness of the method was verified.

Background Cervical cancer (CC) is a common gynecological malignancy worldwide. Some patients perform serious resistance after chemotherapy, and long-stranded non-coding RNA MEG3 is reported to be involved in the regulation of chemoresistance in many solid tumors. However, its involvement in cervical adenocarcinoma has not been reported. Methods Hela cell lines, cisplatin-resistant cell lines (Hela-CR) and nude mice were used in this study. After MEG3 was overexpressed or knocked down in cells by the lentivirus vector, cell growth was detected by the CCK-8 assay, and cell migration was evaluated using Transwell assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of MEG3, miR-21 and PTEN mRNA. Apoptosis was detected by flow cytometry. The targeting relationship between mRNAs was predicted and verified using dual-luciferase reporter gene experiments. Western blot was executed to examine Bax, cleaved-caspase 3, Bcl-2, PTEN and GAPDH expression. Cells were injected into the mice to form xenograft tumors to compare tumorigenesis capacity. Results We demonstrated that MEG3 was down-regulated in cervical cancer by analyzing the TCGA database. Moreover, knockdown of MEG3 promoted CC cell proliferation, migration and inhibited the apoptosis. These changes of CC cells were more pronounced under cisplatin treatment. Further studies showed that the MEG3/miR-21/PTEN axis affected cisplatin sensitivity in cervical cancer cells, and these results of recue assay were used to confirm this conclusion. Conclusions MEG3 performing as ceRNA promotes cisplatin sensitivity in CC cells through the miR-21/PTEN axis.

Antrodia cinnamomea (AC) is a treasured Asian medicinal mushroom, which has attracted attention due to recent research on its effectiveness in targeting a variety of serious ailments such as cancer and liver diseases. Among different A. cinnamomea constituents, triterpenoids are regarded as the most therapeutically attractive components because of their anti-inflammatory and cytotoxic activities. In the present study, we proposed a mathematical and statistical extraction protocol to evaluate the concentrations of total ergostane and lanostane triterpenoid derivatives from the ethanolic extract of the wild fruiting bodies of A. cinnamomea (EEAC) by utilizing response surface methodology (RSM) and quantitative NMR (qNMR) approaches. The optimum response surface model showed that the variations of the investigated response variables reached more than 90%, suggesting that the developed model is accurate in explaining response variability. Furthermore, the EEAC major characteristic triterpenoids were quantified through the comparison of the HPLC-tandem MS results with those of the qNMR results. The precision of the used techniques was also evaluated. The experimental design of the EEAC optimum extraction procedure obtained by using RSM and qNMR enabled accurate characterization and quantitation of A. cinnamomea triterpenoids.

Saxifragaceae, a family of over 600 species and approximately 30 genera of herbaceous perennials, is well-known for intergeneric hybridization. Of the main lineages in this family, the group represents a valuable model for the analysis of plastid capture and its impact on phylogeny reconstruction. In this study, we investigated plastome evolution across the family, reconstructed the phylogeny of the group and examined putative plastid capture between and . Seven species (11 individuals) representing , as well as and , were selected for genome skimming. We assembled the plastomes, and then compared these to six others published for Saxifragaceae; the plastomes were found to be highly similar in overall size, structure, gene order and content. Moreover, 15 was lost due to pseudogenization and 2 lost its only intron for all the analyzed plastomes. Comparative plastome analysis revealed that size variations of the plastomes are purely ascribed to the length differences of LSC, SSC, and IRs regions. Using nuclear ITS + ETS and the complete plastome, we fully resolved the species relationships of , finding that the genus is monophyletic and the Asian species is most closely related to the western North American species. However, the position of the species was highly incongruent between nuclear and plastid data. Comparisons of nuclear and plastid phylogenies revealed that multiple plastid capture events have occurred between and , through putative ancient hybridization. Moreover, we developed numerous molecular markers for (e.g., plastid hotspot and polymorphic nuclear SSRs), which will be useful for future studies on the population genetics and phylogeography of this disjunct genus.

cGAS is an important sensor of cytosolic DNA, but the mechanisms that regulate it remain largely unknown. Fan and colleagues demonstrate that cGAS and its DNA-binding activities are negatively regulated by glutamylation. Cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA during viral infection and catalyzes synthesis of the dinucleotide cGAMP, which activates the adaptor STING to initiate antiviral responses. Here we found that deficiency in the carboxypeptidase CCP5 or CCP6 led to susceptibility to DNA viruses. CCP5 and CCP6 were required for activation of the transcription factor IRF3 and interferons. Polyglutamylation of cGAS by the enzyme TTLL6 impeded its DNA-binding ability, whereas TTLL4-mediated monoglutamylation of cGAS blocked its synthase activity. Conversely, CCP6 removed the polyglutamylation of cGAS, whereas CCP5 hydrolyzed the monoglutamylation of cGAS, which together led to the activation of cGAS. Therefore, glutamylation and deglutamylation of cGAS tightly modulate immune responses to infection with DNA viruses.

We study a quantum absorption refrigerator, in which a target qubit is cooled by two machine qubits in a nonequilibrium steady-state. It is realized by a strong internal coupling in the two-qubit fridge and a vanishing tripartite interaction among the whole system. The coherence of a machine virtual qubit is investigated as quantumness of the fridge. A necessary condition for cooling shows that the quantum coherence is beneficial to the nonequilibrium fridge, while it is detrimental as far as the maximum coefficient of performance (COP) and the COP at maximum power are concerned. Here, the COP is defined only in terms of heat currents caused by the tripartite interaction, with the one maintaining the two-qubit nonequilibrium state being excluded. The later can be considered to have no direct involvement in extracting heat from the target, as it is not affected by the tripartite interaction.

Natural killer (NK) cells exert a crucial role in early immune responses as a major innate effector component. However, the underlying mechanisms of NK cell development remain largely elusive. Here we show that robust autophagy appears in the stage of immature NK cells (iNKs), which is required for NK cell development. Autophagy defects result in damaged mitochondria and accumulation of reactive oxygen species (ROS) that leads to apoptosis of NK cells. Autophagy protects NK cell viability during development through removal of damaged mitochondria and intracellular ROS. Phosphorylated Forkhead box O (FoxO)1 is located to the cytoplasm of iNKs and interacts with Atg7, leading to induction of autophagy. FoxO1 deficiency or an inactive FoxO1 AAA mutant abrogates autophagy initiation in iNKs and impairs NK cell development and viral clearance. Therefore we conclude that FoxO1-mediated autophagy is required for NK cell development and NK cell-induced innate immunity. Natural killer cells are a major component of the innate immune response. Here, Wang et al . show that natural killer cell development requires robust activation of autophagy at the immature stage where it acts to remove damaged mitochondria and reduces levels of reactive oxygen species.