Direct ethanol fuel cells (DEFCs) have great activity as a green energy conversion device. However, the weak activity of most anode electrocatalysts for the CC bond cleavage is an obstacle to the ...DEFCs development. Herein, a simple galvanic replacement reaction strategy to synthesize hollow and porous PtRhCu trimetallic nanoboxes (CNBs) with a tunable Pt/Rh atomic ratio is developed. For the ethanol oxidation reaction (EOR), PtRhCu CNBs show morphology and composition‐dependent electrocatalytic activity. The composition optimized Pt54Rh4Cu42 CNBs exhibit excellent specific and mass activity and stability for the EOR, which is attributed to its unique geometric structure and synergistic effects. The hollow porous structure can effectively enhance the atomic utilization and mass transfer. The introduction of Cu improves the antipoisoning capability for CO. The introduction of Rh elevates the self‐stability of PtRhCu CNBs. More importantly, further electrochemical results confirm that the introduction of Rh significantly promotes the cleavage of CC bonds, leading to the transformation of the main catalytic pathway for EOR from C2 to C1 pathway. The real concentration detection for C2 products (CH3COOH and CH3CHO) shows Pt54Rh4Cu42 CNBs have a nearly 11.5‐fold C1 pathway enhancement compared to Pt nanoparticles, showing an obvious selectivity enhancement for the C1 pathway.
Porous trimetallic PtRhCu cubic nanoboxes (CNBs) are prepared by a universal galvanic replacement reaction strategy. For the ethanol electrooxidation, the component optimized Pt54Rh4C42 CNBs exhibit favorable C1 pathway selectivity and excellent electrocatalytic activity and durability due to its geometric structure and synergistic effects.
Tumor cells with stemness (stem‐cell) features contribute to initiation and progression of hepatocellular carcinoma (HCC), but involvement of long noncoding RNAs (lncRNAs) remains largely unclear. ...Genome‐wide analyses were applied to identify tumor‐associated lncRNA‐DANCR. DANCR expression level and prognostic values of DANCR were assayed in two HCC cohorts (China and Korea, n = 135 and 223). Artificial modulation of DANCR (down‐ and overexpression) was done to explore the role of DANCR in tumorigenesis and colonization, and tumor‐bearing mice were used to determine therapeutic effects. We found that lncRNA‐DANCR is overexpressed in stem‐like HCC cells, and this can serve as a prognostic biomarker for HCC patients. Experiments showed that DANCR markedly increased stemness features of HCC cells to promote tumorigenesis and intra‐/extrahepatic tumor colonization. Conversely, DANCR knockdown attenuated the stem‐cell properties and in vivo interference with DANCR action led to decreased tumor cell vitality, tumor shrinkage, and improved mouse survival. Additionally, we found that the role of DANCR relied largely on an association with, and regulation of, CTNNB1. Association of DANCR with CTNNB1 blocked the repressing effect of microRNA (miR)−214, miR‐320a, and miR‐199a on CTNNB1. This observation was confirmed in vivo, suggesting a novel mechanism of tumorigenesis involving lncRNAs, messenger RNAs, and microRNAs. Conclusions: These studies reveal a significance and mechanism of DANCR action in increasing stemness features and offer a potential prognostic marker and a therapeutic target for HCC. (Hepatology 2016;63:499–511)
The morphology and dimension of the conductive filament formed in a memristive device are strongly influenced by the thickness of its switching medium layer. Aggressive scaling of this active layer ...thickness is critical toward reducing the operating current, voltage, and energy consumption in filamentary‐type memristors. Previously, the thickness of this filament layer has been limited to above a few nanometers due to processing constraints, making it challenging to further suppress the on‐state current and the switching voltage. Here, the formation of conductive filaments in a material medium with sub‐nanometer thickness formed through the oxidation of atomically thin two‐dimensional boron nitride is studied. The resulting memristive device exhibits sub‐nanometer filamentary switching with sub‐pA operation current and femtojoule per bit energy consumption. Furthermore, by confining the filament to the atomic scale, current switching characteristics are observed that are distinct from that in thicker medium due to the profoundly different atomic kinetics. The filament morphology in such an aggressively scaled memristive device is also theoretically explored. These ultralow energy devices are promising for realizing femtojoule and sub‐femtojoule electronic computation, which can be attractive for applications in a wide range of electronics systems that desire ultralow power operation.
A nonvolatile memristive device with a sub‐nanometer thick switching layer, sub‐picoampere operating current, and femtojoule per bit energy consumption is demonstrated. The ultrathin medium layer is formed through the oxidation of atomically thin hexagonal boron nitride. Due to the atomic‐scale confinement of the filament length, current switching characteristics disparate from that in a thicker medium are observed resulting from the distinct ionic kinetics.
To explore whether plasma circular RNAs (circRNAs) can diagnose hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC), microarray and qPCR were used to identify plasma circRNAs that were ...increased in HBV‐related HCC patients compared to controls (including healthy controls, chronic hepatitis B and HBV‐related liver cirrhosis). A logistic regression model was constructed using a training set (n = 313) and then validated using another two independent sets (n = 306 and 526, respectively). Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. We identified a plasma circRNA panel (CircPanel) containing three circRNAs (hsa_circ_0000976, hsa_circ_0007750 and hsa_circ_0139897) that could detect HCC. CircPanel showed a higher accuracy than AFP (alpha‐fetoprotein) to distinguish individuals with HCC from controls in all three sets (AUC, 0.863 95% confidence interval, CI: 0.819–0.907 vs. 0.790 0.738–0.842, p = 0.036 in training set; 0.843 0.796–0.890 vs. 0.747 0.691–0.804, p = 0.011 in validation set 1 and 0.864 0.830–0.898 vs. 0.769 0.728–0.810, p < 0.001 in validation set 2). CircPanel also performed well in detecting Small‐HCC (solitary, ≤3 cm), AFP‐negative HCC and AFP‐negative Small‐HCC.
What's new?
To date, one limitation in the treatment of hepatocellular carcinoma (HCC) is the lack of serum biomarkers with satisfactory diagnostic accuracy. Here, the authors explored whether plasma circRNAs can be biomarkers to diagnose hepatitis B virus‐related HCC in 1155 participants from three hospitals in China. They identified a plasma circRNA panel (CircPanel, including hsa_circ_0000976, hsa_circ_0007750, and hsa_circ_0139897) that showed higher accuracy than the clinically‐used serum biomarker AFP in distinguishing individuals with HCC or Small‐HCC from controls and performed well in diagnosing AFP‐negative HCC and AFP‐negative Small‐HCC. Altogether, the findings point to CircPanel as a promising potential biomarker in HCC diagnosis.
In 2017, surveillance for tickborne diseases in China led to the identification of a patient who presented to a hospital in Inner Mongolia with a febrile illness that had an unknown cause. The ...clinical manifestation of the illness was similar to that of tickborne encephalitis virus (TBEV) infection, but neither TBEV RNA nor antibodies against the virus were detected.
We obtained a blood specimen from the index patient and attempted to isolate and identify a causative pathogen, using genome sequence analysis and electron microscopy. We also initiated a heightened surveillance program in the same hospital to screen for other patients who presented with fever, headache, and a history of tick bites. We used reverse-transcriptase-polymerase-chain-reaction (RT-PCR) and cell-culture assays to detect the pathogen and immunofluorescence and neutralization assays to determine the levels of virus-specific antibodies in serum specimens from the patients.
We found that the index patient was infected with a previously unknown segmented RNA virus, which we designated Alongshan virus (ALSV) and which belongs to the jingmenvirus group of the family Flaviviridae. ALSV infection was confirmed by RT-PCR assay in 86 patients from Inner Mongolia and Heilongjiang who presented with fever, headache, and a history of tick bites. Serologic assays showed that seroconversion had occurred in all 19 patients for whom specimens were available from the acute phase and the convalescent phase of the illness.
A newly discovered segmented virus was found to be associated with a febrile illness in northeastern China. (Funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China.).
Understanding the roles of splicing factors and splicing events during tumorigenesis would open new avenues for targeted therapies. Here we identify an oncofetal splicing factor, MBNL3, which ...promotes tumorigenesis and indicates poor prognosis of hepatocellular carcinoma patients. MBNL3 knockdown almost completely abolishes hepatocellular carcinoma tumorigenesis. Transcriptomic analysis revealed that MBNL3 induces lncRNA-PXN-AS1 exon 4 inclusion. The transcript lacking exon 4 binds to coding sequences of PXN mRNA, causes dissociation of translation elongation factors from PXN mRNA, and thereby inhibits PXN mRNA translation. In contrast, the transcript containing exon 4 preferentially binds to the 3' untranslated region of PXN mRNA, protects PXN mRNA from microRNA-24-AGO2 complex-induced degradation, and thereby increases PXN expression. Through inducing exon 4 inclusion, MBNL3 upregulates PXN, which mediates the pro-tumorigenic roles of MBNL3. Collectively, these data demonstrate detailed mechanistic links between an oncofetal splicing factor, a splicing event and tumorigenesis, and establish splicing factors and splicing events as potential therapeutic targets.
N
-Methyladenosine (m
A) modification has been implicated in many biological processes. However, its role in cancer has not been well studied. Here, we demonstrate that m
A modifications are ...decreased in hepatocellular carcinoma, especially in metastatic hepatocellular carcinoma, and that methyltransferase-like 14 (METTL14) is the main factor involved in aberrant m
A modification. Moreover, METTL14 down-regulation acts as an adverse prognosis factor for recurrence-free survival of hepatocellular carcinoma and is significantly associated with tumor metastasis in vitro and in vivo. We confirm that METTL14 interacts with the microprocessor protein DGCR8 and positively modulates the primary microRNA 126 process in an m
A-dependent manner. Further experiments show that microRNA 126 inhibits the repressing effect of METTL14 in tumor metastasis.
These studies reveal an important role of METTL14 in tumor metastasis and provide a fresh view on m
A modification in tumor progression. (Hepatology 2017;65:529-543).
There have been a large number of reports about glial cell dysfunction being related to major psychiatric diseases such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder ...(MDD). In this review, we provide an overview of postmortem studies analyzing the structural changes of glial cells in these three major psychiatric diseases, including the density, number and size of glial cells, and the expression of related markers. Up to May 1, 2021, 108 articles that met the inclusion criteria were identified by searching PubMed and Web of Science. Although most studies evaluating total glial cells did not show abnormalities in the brains of postmortem patients, astrocytes, microglial cells, and oligodendrocytes seem to have specific patterns of changes in each disease. For example, out of 20 studies that evaluated astrocyte markers in MDD, 11 studies found decreased astrocyte marker expression in MDD patients. Similarly, out of 25 studies evaluating oligodendrocyte markers in SCZ, 15 studies showed decreased expression of oligodendrocyte markers in different brain regions of SCZ patients. In addition, activated microglial cells were observed in patients with SCZ, BD, and MDD, but suicide may be a confounding factor for the observed effects. Although the data from the included studies were heterogeneous and this cannot be fully explained at present, it is likely that there are a variety of contributing factors, including the measured brain regions, methods of measurement, gender, age at time of death, and medications.
Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this ...study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis-associated gallbladder cancer lncRNA (lncRNA-PAGBC), which we find to be an independent prognostic marker in GBC. Functional analysis indicates that lncRNA-PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA-PAGBC competitively binds to the tumour suppressive microRNAs miR-133b and miR-511. This competitive role of lncRNA-PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA-PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC.
Synopsis
Long noncoding RNAs play roles in the development and progression of many cancers. In this study the lncRNA PAGBC is identified as promoting tumorigenesis in human gallbladder cancer by competitive binding to the tumour suppressive microRNAs miR-133b and miR-511.
LncRNA-PAGBC is up-regulated in GBC and increased levels associate with poor prognosis.
LncRNA-PAGBC promotes tumour growth and metastasis, and activates AKT/mTOR signaling by competitively binding to mirR-133b and mirR-511.
LncRNA-PAGBC interacts with and is stabilized by the polyadenylate binding protein PABPC1.
Graphical Abstract
Long noncoding RNAs play roles in the development and progression of many cancers. In this study the lncRNA PAGBC is identified as promoting tumorigenesis in human gallbladder cancer by competitive binding to the tumour suppressive microRNAs miR-133b and miR-511.
Abstract
Exosomes have been suggested as promising targets for the diagnosis and treatment of neurological diseases, including schizophrenia (SCZ), but the potential role of exosome-derived ...metabolites in these diseases was rarely studied. Using ultra-performance liquid chromatography-tandem mass spectrometry, we performed the first metabolomic study of serum-derived exosomes from patients with SCZ. Our sample comprised 385 patients and 332 healthy controls recruited from 3 clinical centers and 4 independent cohorts. We identified 25 perturbed metabolites in patients that can be used to classify samples from patients and control participants with 95.7% accuracy (95% CI: 92.6%–98.9%) in the training samples (78 patients and 66 controls). These metabolites also showed good to excellent performance in differentiating between patients and controls in the 3 test sets of participants, with accuracies 91.0% (95% CI: 85.7%–96.3%; 107 patients and 62 controls), 82.7% (95% CI: 77.6%–87.9%; 104 patients and 142 controls), and 99.0% (95% CI: 97.7%–100%; 96 patients and 62 controls), respectively. Bioinformatic analysis suggested that these metabolites were enriched in pathways implicated in SCZ, such as glycerophospholipid metabolism. Taken together, our findings support a role for exosomal metabolite dysregulation in the pathophysiology of SCZ and indicate a strong potential for exosome-derived metabolites to inform the diagnosis of SCZ.
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