Lung cancer is the main cause of cancer‐related death, and the proportion of non–small cell lung cancer (NSCLC) on lung cancer is 85%, while more than 80% lung cancer patients are diagnosed with ...chronic obstructive pulmonary disease (COPD). In this study, we aimed to explore the potential mechanism of COPD induced NSCLC. Luciferase assay and reverse transcription‐polymerase chain reaction (RT‐PCR) were conducted to study the regulatory relationship between P53 and microRNA‐675 (miR‐675). Real‐time PCR, Western‐blot analysis, and MTT assay were performed to explore the impact of H19 and miR‐675 in the signaling pathway involved in COPD induced NSCLC. In NSCLC patients with COPD, H19 and miR‐675 levels were strikingly upregulated while P53 level was significantly downregulated. P53 was identified as a target gene of miR‐675, and H19 remarkably upregulated miR‐675, while H19 siRNA notably inhibited miR‐675. In addition, miR‐675 and H19 dramatically suppressed the expression of P53 and Bax while inducing the expression of Bcl‐2. Finally, H19 and miR‐675 induced proliferation of A549 and MRC‐5 cells. These finding indicated that COPD (hypoxia)‐induced H19 promoted expression of miR‐675 associated with NSCLC though target apoptosis‐related protein P53, BAX, and Bcl‐2.
Lung cancer is the main cause of cancer‐related death, and the proportion of non–small cell lung cancer (NSCLC) on lung cancer is 85%, and more than 80% patients with lung cancer also diagnosed with chronic obstructive pulmonary disease (COPD), and the risk of lung cancer in patients with COPD was much higher, we aimed to explore the potential mechanism of COPD induced NSCLC. And our findings indicated that COPD (hypoxia)‐induced H19 promoted expression of microRNA‐675 associated with NSCLC though target apoptosis‐related protein P53, BAX, and Bcl‐2.
Liver cancer stem cells (LCSCs) are a small subset of cells characterized by unlimited self-renewal, cell differentiation, and uncontrollable cellular growth. LCSCs are also resistant to conventional ...therapies and are thus believed to be held responsible for causing treatment failure of hepatocellular carcinoma (HCC). It has been recently found that long non-coding RNAs (lncRNAs) are important regulators in HCC. This present study aims to explore the underlying mechanism of how lncRNA DLX6-AS1 influences the development of LCSCs and HCC.
A microarray-based analysis was performed to initially screen differentially expressed lncRNAs associated with HCC. We then analyzed the lncRNA DLX6-AS1 levels as well as CADM1 promoter methylation. The mRNA and protein expression of CADM1, STAT3, CD133, CD13, OCT-4, SOX2, and Nanog were then detected. We quantified our results by evaluating the spheroid formation, proliferation, and tumor formation abilities, as well as the proportion of tumor stem cells, and the recruitment of DNA methyltransferase (DNMT) in LCSCs when lncRNA DLX6-AS1 was either overexpressed or silenced.
LncRNA DLX6-AS1 was upregulated in HCC. The silencing of lncRNA DLX6-AS1 was shown to reduce and inhibit spheroid formation, colony formation, proliferation, and tumor formation abilities, as well as attenuate CD133, CD13, OCT-4, SOX2, and Nanog expression in LCSCs. Furthermore, downregulation of lncRNA DLX6-AS1 contributed to a reduction in CADM1 promoter methylation via suppression of DNMT1, DNMT3a, and DNMT3b in LCSCs and inactivating the STAT3 signaling pathway.
This study demonstrated that down-regulated lncRNA DLX6-AS1 may inhibit the stem cell properties of LCSCs through upregulation of CADM1 by suppressing the methylation of the CADM1 promoter and inactivation of the STAT3 signaling pathway.
Abstract
Sodium metal batteries (SMBs) using gel polymer electrolytes (GPEs) with high theoretical capacity and low production cost are regarded as a promising candidate for high energy‐density ...batteries. However, the inherent flammability of GPEs and uncontrolled Na dendrite caused by inferior mechanical properties and interfacial stability hinder their practical applications. Herein, an anion‐trapping fireproof composite gel electrolyte (AT‐FCGE) is designed through a chemical grafting–coupling strategy, where functionalized boron nitride nanosheets (M‐BNNs) used as both nanosized crosslinker and anion capturer are coupled with poly(ethylene glycol)diacrylate in poly(vinylidene fluoride‐co‐hexafluoropropylene) matrix, to expedite Na
+
transport and suppress dendrite growth. Experimental and calculation studies suggest that the anion‐trapping effect of M‐BNNs with abundant Lewis‐acid sites can promote the dissociation of salts, thus remarkably improving the ionic conductivity and Na
+
transference number. Meanwhile, the formation of highly crosslinked semi‐interpenetrating network can effectively in situ encapsulate non‐flammable phosphate without sacrificing the mechanical properties. Consequently, the resulting AT‐FCGE shows significantly enhanced Na
+
conductivity, mechanical properties, and excellent interfacial stability. The AT‐FCGE enables a long‐cycle stability dendrite‐free Na/Na symmetric cell, and prominent electrochemical performance is demonstrated in solid‐state SMBs. The approach provides a broader promise for the great potential of fire‐retardant gel electrolytes in high‐performance SMBs and the beyond.
Organic materials with multi‐stimulus response (MSR) properties have demonstrated many potential and practical applications. Herein, a π‐stacked thermally activated delayed fluorescence (TADF) ...material with multi‐stimulus response (MSR) properties, named SDMAC, was designed and synthesized using distorted 9,9‐dimethyl‐10‐phenyl‐9,10‐dihydroacridine as a donor. SDMAC possesses a rigid π‐stacked configuration with intramolecular through‐space interactions and exhibits aggregation‐induced emission enhancement (AIEE), solvatochromic, piezochromic, and circularly polarized luminescence (CPL) under different external stimuli. The rigid molecular structure and efficient TADF properties of SDMAC can be used in displays and lighting. Using SDMAC as an emitter, the maximum external quantum efficiency (EQE) of the fabricated organic light‐emitting diodes (OLEDs) is as high as 28.4 %, which make them the most efficient CP‐TADF OLEDs based on the through‐space charge transfer strategy. The CP organic light‐emitting diodes (CP‐OLEDs) exhibit circularly polarized electroluminescence (CPEL) signals.
An efficient thermally activated delayed fluorescence (TADF) emitter has been developed that possesses a rigid π‐stacked configuration with intramolecular through‐space interactions. This emitter exhibits solvatochromism, piezochromism, aggregation‐induced emission enhancement (AIEE), and circularly polarized luminescence (CPL) under different external stimuli.
Over the past decade, lncRNAs have been widely reported in human malignant tumors, including papillary thyroid carcinoma. LncRNA SNHG15 has been validated to be a tumor facilitator in several types ...of malignancies. The present study focused on the biological role of SNHG15 in papillary thyroid carcinoma. Based on the result of qPCR analysis, we identified the strong expression of SNHG15 in human papillary thyroid carcinoma tissues and cell lines. Moreover, Kaplan-Meier method was utilized to analyze the internal relevance between SNHG15 expression and overall survival rate of patients with papillary thyroid carcinoma. Loss-of-function assays were designed and conducted to determine the inhibitory effects of silenced SNHG15 on the cell growth and migration in papillary thyroid carcinoma. The mechanical investigation indicated that SNHG15 upregulated YAP1 by sponging miR-200a-3p. Moreover, results of gain-of-function assays validated the anti-oncogenic function of miR-200a-3p in papillary thyroid carcinoma. Finally, results of rescue assays validated the function of SNHG15-miR-200a-3p-YAP1 axis in papillary thyroid carcinoma. YAP1 is known as an oncogene and a core factor of Hippo pathway. Here, we demonstrated that SNHG15 inactivated Hippo signaling pathway in papillary thyroid carcinoma. In summary, our findings demonstrated that SNHG15 serves as a competitively endogenous RNA (ceRNA) to regulate YAP1-Hippo signaling pathway by sponging miR-200a-3p in papillary thyroid carcinoma.
Abstract
Background
Super-enhancers (SEs) play a crucial role in cancer, which is often associate with activated oncogenes. However, little is known about how SEs facilitate tumour suppression. ...Individuals with Down syndrome exhibit a remarkably reduced incidence of breast cancer (BC), moving the search for tumor suppressor genes on human chromosome 21 (HSA21). In this study, we aim to identify and explore potential mechanisms by which SEs are established for tumor suppressor RCAN1.4 on HSA21 in BC.
Methods
In silico analysis and immunohistochemical staining were used to assess the expression and clinical relevance of RCAN1.4 and RUNX3 in BC. Function experiments were performed to evaluate the effects of RCAN1.4 on the malignancy of breast carcinoma in vitro and in vivo. ChIP-seq data analysis, ChIP-qPCR, double-CRISPR genome editing, and luciferase reporter assay were utilized to confirm RUNX3 was involved in regulating RCAN1.4-associated SE in BC. The clinical value of co-expression of RCAN1.4 and RUNX3 was evaluated in BC patients.
Results
Here, we characterized RCAN1.4 as a potential tumour suppressor in BC. RCAN1.4 loss promoted tumour metastasis to bone and brain, and its overexpression inhibited tumour growth by blocking the calcineurin-NFATc1 pathway. Unexpectedly, we found RCAN1.4 expression was driven by a ~ 23 kb-long SE. RCAN1.4-SE
distal
was sensitive to BRD4 inhibition, and its deletion decreased RCAN1.4 expression by over 90% and induced the malignant phenotype of BC cells. We also discovered that the binding sites in the SE region of RCAN1.4 were enriched for consensus sequences of transcription factor RUNX3. Knockdown of RUNX3 repressed the luciferase activity and also decreased H3K27ac enrichment binding at the SE region of RCAN1.4. Furthermore, abnormal SE-driven RCAN1.4 expression mediated by RUNX3 loss could be physiologically significant and clinically relevant in BC patients. Notably, we established a prognostic model based on RCAN1.4 and RUNX3 co-expression that effectively predicted the overall survival in BC patients.
Conclusions
These findings reveal an important role of SEs in facilitating tumour suppression in BC. Considering that the combination of low RCAN1.4 and low RUNX3 expression has worse prognosis, RUNX3-RCAN1.4 axis maybe a novel prognostic biomarker and therapeutic target for BC patients.
Amplitude of low‐frequency fluctuation (ALFF) has been widely used for localization of abnormal activity at the single‐voxel level in resting‐state fMRI (RS‐fMRI) studies. However, previous ALFF ...studies were based on fast Fourier transform (FFT‐ALFF). Our recent study found that ALFF based on wavelet transform (Wavelet‐ALFF) showed better sensitivity and reproducibility than FFT‐ALFF. The current study aimed to test the reliability and validity of Wavelet‐ALFF, and apply Wavelet‐ALFF to investigate the modulation effect of repetitive transcranial magnetic stimulation (rTMS). The reliability and validity were assessed on multicenter RS‐fMRI datasets under eyes closed (EC) and eyes open (EO) conditions (248 healthy participants in total). We then detected the sensitivity of Wavelet‐ALFF using a rTMS modulation dataset (24 healthy participants). For each dataset, Wavelet‐ALFF based on five mother wavelets (i.e., db2, bior4.4, morl, meyr and sym3) and FFT‐ALFF were calculated in the conventional band and five frequency sub‐bands. The results showed that the reliability of both inter‐scanner and intra‐scanner was higher with Wavelet‐ALFF than with FFT‐ALFF across multiple frequency bands, especially db2‐ALFF in the higher frequency band slow‐2 (0.1992–0.25 Hz). In terms of validity, the multicenter ECEO datasets showed that the effect sizes of Wavelet‐ALFF with all mother wavelets (especially for db2‐ALFF) were larger than those of FFT‐ALFF across multiple frequency bands. Furthermore, Wavelet‐ALFF detected a larger modulation effect than FFT‐ALFF. Collectively, Wavelet db2‐ALFF showed the best reliability and validity, suggesting that db2‐ALFF may offer a powerful metric for inspecting regional spontaneous brain activities in future studies.
Using multicenter RS‐fMRI datasets under EC and EO conditions and a single‐session rTMS modulation dataset, this study provides evidence of the superiority of Wavelet‐ALFF (especially db2‐ALFF) over FFT‐ALFF in improving reliability and validity and increasing statistical significance. Therefore, db2‐ALFF may offer a powerful metric for inspecting regional spontaneous brain activities in future studies.
Human exposure to formaldehyde, toluene, xylene (FTX) and other volatile organic compounds (VOCs) are associated with negative health impact. To characterize the exposure and health effects of FTX ...and TVOC from indoor environments, we conducted an extensive monitoring campaign involving 1278 measurements of 472 indoor locations in Harbin, a megacity in China from May 2013 to March 2018. The results showed that household had the highest mean formaldehyde concentration (0.171 ± 0.084 mg m-3) among all types of indoor environments. Meanwhile, there was no significant differences in formaldehyde concentration of the living room, master bedroom, secondary bedroom and study room (p > 0.05), as well as toluene and xylene. The highest mean concentration of toluene, xylene and TVOC was measured in public bath center. Great difference was found between formaldehyde concentrations in 2013 and other years, except 2015. There were great positive nonlinear correlations between the indoor temperature and concentration of formaldehyde (p < 0.01), good negative nonlinear correlations between the finish time of decoration and concentration of formaldehyde (p < 0.01), good positive linear correlations between the relative humidity and concentration of formaldehyde (p < 0.01). A risk assessment methodology was utilized to evaluate the potential adverse health effects of the individual FTX compounds according to their carcinogenicities. The predicted carcinogenic risk of formaldehyde was greater than the threshold value 1E-06 at all environments. The non-carcinogenic risk of TX compounds in the population is negligible. For estimating human health risk exposure, sensitivity analysis showed that more attention should be given to the influential variables such as the level of pollutants.
•SConducted an extensive monitoring campaign in Harbin, from May 2013 to March 2018.•There were correlations between the indoor temperature, relative humidity, finish time of decoration and concentration of formaldehyde.•The predicted carcinogenic risk of formaldehyde was greater than the threshold value at all microenvironments.
Circular RNAs (circRNAs) have been reported to have critical regulatory roles in tumor biology. However, their contribution to melanoma remains largely unknown.
CircRNAs derived from oncogene CD151 ...were detected and verified by analyzing a large number of melanoma samples through quantitative real-time polymerase chain reaction (qRT-PCR). Melanoma cells were stably transfected with lentiviruses using circ_0020710 interference or overexpression plasmid, and then CCK-8, colony formation, wound healing, transwell invasion assays, and mouse xenograft models were employed to assess the potential role of circ_0020710. RNA immunoprecipitation, luciferase reporter assay and fluorescence in situ hybridization were used to evaluate the underlying mechanism of circ_0020710.
Our findings indicated that circ_0020710 was generally overexpressed in melanoma tissues, and high level of circ_0020710 was positively correlated with malignant phenotype and poor prognosis of melanoma patients. Elevated circ_0020710 promoted melanoma cell proliferation, migration and invasion in vitro as well as tumor growth in vivo. Mechanistically, we found that high level of circ_0020710 could upregulate the CXCL12 expression via sponging miR-370-3p. CXCL12 downregulation could reverse the malignant behavior of melanoma cells conferred by circ_0020710 over expression. Moreover, we also found that elevated circ_0020710 was correlated with cytotoxic lymphocyte exhaustion, and a combination of AMD3100 (the CXCL12/CXCR4 axis inhibitor) and anti-PD-1 significantly attenuated tumor growth.
Elevated circ_0020710 drives tumor progression via the miR-370-3p/CXCL12 axis, and circ_0020710 is a potential target for melanoma treatment.
This work elucidates the potential impact of intramolecular H-bonds within the pore walls of covalent organic frameworks (COFs) on proton conductivity. Employing DaTta and TaTta as representative ...hosts, it was observed that their innate proton conductivities (σ) are both unsatisfactory and σ(DaTta) < σ(TaTta). Intriguingly, the performance of both imidazole-loaded products, Im@DaTta and Im@TaTta is greatly improved, and the σ of Im@DaTta (0.91 × 10-2 S·cm-1) even surpasses that of Im@TaTta (3.73 × 10-3 S·cm-1) under 100 °C and 98% relative humidity. The structural analysis, gas adsorption tests, and activation energy calculations forecast the influence of imidazole on the H-bonded system within the framework, leading to observed changes in proton conductivity. It is hypothesized that intramolecular H-bonds within the COF framework impede efficient proton transmission. Nevertheless, the inclusion of an imidazole group disrupts these intramolecular bonds, leading to the formation of an abundance of intermolecular H-bonds within the pore channels, thus contributing to a dramatic increase in proton conductivity. The related calculation of Density Functional Theory (DFT) provides further evidence for this inference.
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