We present a comprehensive mechanistic study on the highly tunable selectivity over In x /ZrO2 catalysts in CO2 hydrogenation. By variation of the indium loading between 0.1 and 5 wt %, either an ...admirable selectivity to methanol of 70–80% or up to 80% selectivity to CO could be obtained in the temperature range of 250–280 °C. It is shown that the shift in the product spectrum is related to the synergy between indium species and the zirconia substrate through variable interfacial structures. Zirconia-modulated crystalline In2O3, which prevails for indium loadings between 2.5 and 5 wt %, could enhance stepwise hydrogenation of *HCOO, leading to *H3CO and finally methanol due to the suitable bonding strengths of *HCOO and *H3CO. Regarding CO, evidence has been provided that the synergistic effect between adjacent indium and zirconia sites is indispensable for the entire catalytic cycle. *HCOO is formed at the indium–zirconia interfaces and decomposes to CO subsequently. Highly dispersed InO x dominating for loadings below 0.5 wt % features an enormous indium–zirconia interface and suppresses hydrogenation ability for *HCOO, thus favoring the generation of CO. The study provides fundamental insights into the mechanism of CO2 conversion and reaction pathway tuning over oxide catalytic systems.
Breast cancer (BC) is the most prevalent malignant cancer in the world, is the leading cause of cancer‐related death female. Recently, there is accumulating evidence that long noncoding RNAs ...(lncRNAs) might as an important role in the progression of BC. (epithelial‐mesenchymal transition (EMT) is considered to play a vital role in tumor cells migration and invasion. Nevertheless, the entire biological mechanisms and functions of lncRNAs in tumor migration, invasion, and EMT remain uncertain. In the present research, we observed that the expression of lncRNA AC073284.4 was downregulated in BC paclitaxel‐resistant (PR) cells (MCF‐7/PR) and tissues. Bioinformatics analysis predicted that miR‐18b‐5p was a direct target of AC073284.4, which has been validated by dual‐luciferase reporter gene assay. We further proved that AC073284.4 could directly bind to miR‐18b‐5p and relieve the suppression for dedicator of cytokinesis protein 4 (DOCK4). Furthermore, the underlying functional experiments demonstrated that AC073284.4 might sponge miR‐18b‐5p to attenuate the invasion, metastasis, and EMT of BC cell through upregulating DOCK4 expression. In summary, AC073284.4 might serve as a competing endogenous RNA (ceRNA) in BC progression via modulating miR‐18b‐5p/DOCK4 axis, which weakens EMT and migration of BC. These results suggesting that AC073284.4 might function as a potential novel diagnostic biomarker in the progression of BC.
These findings provide a novel mechanism of the AC073284.4/miR‐18‐5p/DOCK4 axis in breast cancer, especially to explore its role in invasion, metastasis, and EMT, and suggest that this pathway might be a promising molecular therapeutic target against human breast cancer.
As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. ...The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus.
In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model. The next generation matrix approach was adopted to calculate the basic reproduction number (R
) from the RP model to assess the transmissibility of the SARS-CoV-2.
The value of R
was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58.
Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea.
Asthma is a common chronic respiratory disease worldwide. Recent studies have revealed the critical effects of the ceRNA network and ferroptosis on patients with asthma. Thus, this study aimed to ...explore the potential ferroptosis-related ceRNA network, investigate the immune cell infiltration level in asthma through integrated analysis of public asthma microarray datasets, and find suitable diagnostic biomarkers for asthma.
First, three asthma-related datasets which were downloaded from the Gene Expression Omnibus (GEO) database were integrated into one pooled dataset after correcting for batch effects. Next, we screened differentially expressed lncRNAs (DElncRNAs) between patients and healthy subjects, constructed a ceRNA network using the StarBase database and screened ferroptosis-related genes from the predicted target mRNAs for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We also performed Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) on the batch effect-corrected mRNA expression profile. Then, Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to screen potential diagnostic biomarkers, and the diagnostic efficacy was assessed using a receiver operating characteristic (ROC) curve. Finally, we determined the proportion of 22 immune cells in patients with asthma using CIBERSORT and investigated the correlation between key RNAs and immune cells.
We obtained 19 DElncRNAs, of which only LUCAT1 and MIR222HG had corresponding target miRNAs. The differentially expressed ferroptosis-related genes were involved in multiple programmed cell death-related pathways. We also found that the mRNA expression profile was primarily enriched in innate immune system responses. We screened seven candidate diagnostic biomarkers for asthma using LASSO regression (namely, BCL10, CD300E, IER2, MMP13, OAF, TBC1D3, and TMEM151A), among which the area under the curve (AUC) value for CD300E and IER2 were 0.722 and 0.856, respectively. Finally, we revealed the infiltration ratio of different immune cells in asthma and found a correlation between LUCAT1, MIR222HG, CD300E, and IER2 with some immune cells.
This study explored a potential lncRNA-miRNA-mRNA regulatory network and its underlying diagnostic biomarkers (CD300E and IER2) in asthma and identified the immune cells most associated with them, providing possible diagnostic markers and immunotherapeutic targets for asthma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Noncoding RNAs (ncRNAs) represent a large segment of the human transcriptome and have been shown to play important roles in cellular physiology and disease pathogenesis. Increasing evidence on the ...functional roles of ncRNAs in cancer progression emphasizes the potential of ncRNAs for cancer treatment. Here, we summarize the roles of ncRNAs in disease relapse and resistance to current standard chemotherapy and radiotherapy; the current research progress on ncRNAs for clinical and/or potential translational applications, including the identification of ncRNAs as therapeutic targets; therapeutic approaches for ncRNA targeting; and ncRNA delivery strategies in potential clinical translation. Several ongoing clinical trials of novel RNA-based therapeutics were also emphasized. Finally, we discussed the perspectives and obstacles to different target combinations, delivery strategies, and system designs for ncRNA application. The next approved nucleic acid drug to treat cancer patients may realistically be on the horizon.
N6-methyladenosine (m6A) has emerged as an abundant modification throughout the transcriptome with widespread functions in protein-coding and noncoding RNAs. It affects the fates of modified RNAs, ...including their stability, splicing, and/or translation, and thus plays important roles in posttranscriptional regulation. To date, m6A methyltransferases have been reported to execute m6A deposition on distinct RNAs by their own or forming different complexes with additional partner proteins. In this review, we summarize the function of these m6A methyltransferases or complexes in regulating the key genes and pathways of cancer biology. We also highlight the progress in the use of m6A methyltransferases in mediating therapy resistance, including chemotherapy, targeted therapy, immunotherapy and radiotherapy. Finally, we discuss the current approaches and clinical potential of m6A methyltransferase-targeting strategies. Keywords: m6A, m6A methyltransferase, Cancer, Therapy resistance, Drug discovery
Photocatalytic conversion of diluted CO2 into solar fuel is highly appealing yet still in its infancy. Herein, we demonstrate the metal‐node‐dependent performance for photoreduction of diluted CO2 by ...constructing Ni metal–organic framework (MOF) monolayers (Ni MOLs). In diluted CO2 (10 %), Ni MOLs exhibit a highest apparent quantum yield of 1.96 % with a CO selectivity of 96.8 %, which not only exceeds reported systems in diluted CO2 but also is superior to most catalysts in pure CO2. Whereas isostructural Co MOLs is almost inactive in diluted CO2, indicating the performance is dependent on the metal nodes. Experimental and theoretical investigations show that strong CO2 binding affinity of Ni MOLs is the crucial factor, which stabilizes the Ni‐CO2 adducts and facilitates CO2‐to‐CO conversion.
Doctor node: Photocatalytic conversion of diluted CO2 with high efficiency and selectivity can be achieved on Ni metal–organic framework (MOF) monolayers (Ni MOLs). The initial adsorption of CO2 molecules is the critical step and depends on the nature of the metal node.
MAVS and MITA are essential adaptor proteins mediating innate antiviral immune responses against RNA and DNA viruses, respectively. Here we show that RNF115 plays dual roles in response to RNA or DNA ...virus infections by catalyzing distinct types of ubiquitination of MAVS and MITA at different phases of viral infection. RNF115 constitutively interacts with and induces K48-linked ubiquitination and proteasomal degradation of homeostatic MAVS in uninfected cells, whereas associates with and catalyzes K63-linked ubiquitination of MITA after HSV-1 infection. Consistently, the protein levels of MAVS are substantially increased in Rnf115
organs or cells without viral infection, and HSV-1-induced aggregation of MITA is impaired in Rnf115
cells compared to the wild-type counterparts. Consequently, the Rnf115
mice exhibit hypo- and hyper-sensitivity to EMCV and HSV-1 infection, respectively. These findings highlight dual regulation of cellular antiviral responses by RNF115-mediated ubiquitination of MAVS and MITA and contribute to our understanding of innate immune signaling.
Many existing data center network (DCN) flow scheduling schemes, that minimize flow completion times (FCT) assume prior knowledge of flows and custom switch functions, making them superior in ...performance but hard to implement in practice. By contrast, we seek to minimize FCT with no prior knowledge and existing commodity switch hardware. To this end, we present PIAS, a DCN flow scheduling mechanism that aims to minimize FCT by mimicking shortest job first (SJF) on the premise that flow size is not known a priori. At its heart, PIAS leverages multiple priority queues available in existing commodity switches to implement a multiple level feedback queue, in which a PIAS flow is gradually demoted from higher-priority queues to lower-priority queues based on the number of bytes it has sent. As a result, short flows are likely to be finished in the first few high-priority queues and thus be prioritized over long flows in general, which enables PIAS to emulate SJF without knowing flow sizes beforehand. We have implemented a PIAS prototype and evaluated PIAS through both testbed experiments and ns-2 simulations. We show that PIAS is readily deployable with commodity switches and backward compatible with legacy TCP/IP stacks. Our evaluation results show that PIAS significantly outperforms existing information-agnostic schemes, for example, it reduces FCT by up to 50% compared to DCTCP and L2DCT; and it only has a 1.1% performance gap to an ideal information-aware scheme, pFabric, for short flows under a production DCN workload.
There is an exciting possibility to decentralize ammonia synthesis for fertilizer production or energy storage without carbon emission from H2 obtained from renewables at small units operated at ...lower pressure. However, no suitable catalyst has yet been developed. Ru catalysts are known to be promoted by heavier alkali dopants. Instead of using heavy alkali metals, Li is herein shown to give the highest rate through surface polarisation despite its poorest electron donating ability. This exceptional promotion rate makes Ru–Li catalysts suitable for ammonia synthesis, which outclasses industrial Fe counterparts by at least 195 fold. Akin to enzyme catalysis, it is for the first time shown that Ru–Li catalysts hydrogenate end‐on adsorbed N2 stabilized by Li+ on Ru terrace sites to ammonia in a stepwise manner, in contrast to typical N2 dissociation on stepped sites adopted by Ru–Cs counterparts, giving new insights in activating N2 by metallic catalysts.
Lithium treatment: Introduction of Li+ on Ru‐based catalysts can polarize and stabilize adsorbed dinitrogen on the metal surface, which facilitates the non‐dissociative pathway to produce ammonia under mild conditions. The Li–Ru catalysts are suitable for new green ammonia synthesis at lower pressure, and many times better than the commercial Fe counterparts.
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