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"Dong, Yue"
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A circRNA–miRNA–mRNA network identification for exploring underlying pathogenesis and therapy strategy of hepatocellular carcinoma
Background
Circular RNAs (circRNAs) have received increasing attention in human tumor research. However, there are still a large number of unknown circRNAs that need to be deciphered. The aim of this study is to unearth novel circRNAs as well as their action mechanisms in hepatocellular carcinoma (HCC).
Methods
A combinative strategy of big data mining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and computational biology was employed to dig HCC-related circRNAs and to explore their potential action mechanisms. A connectivity map (CMap) analysis was conducted to identify potential therapeutic agents for HCC.
Results
Six differently expressed circRNAs were obtained from three Gene Expression Omnibus microarray datasets (GSE78520, GSE94508 and GSE97332) using the RobustRankAggreg method. Following the RT-qPCR corroboration, three circRNAs (hsa_circRNA_102166, hsa_circRNA_100291 and hsa_circRNA_104515) were selected for further analysis. miRNA response elements of the three circRNAs were predicted. Five circRNA–miRNA interactions including two circRNAs (hsa_circRNA_104515 and hsa_circRNA_100291) and five miRNAs (hsa-miR-1303, hsa-miR-142-5p, hsa-miR-877-5p, hsa-miR-583 and hsa-miR-1276) were identified. Then, 1424 target genes of the above five miRNAs and 3278 differently expressed genes (DEGs) on HCC were collected. By intersecting the miRNA target genes and the DEGs, we acquired 172 overlapped genes. A protein–protein interaction network based on the 172 genes was established, with seven hubgenes (JUN, MYCN, AR, ESR1, FOXO1, IGF1 and CD34) determined from the network. The Gene Oncology, Kyoto Encyclopedia of Genes and Genomes and Reactome enrichment analyses revealed that the seven hubgenes were linked with some cancer-related biological functions and pathways. Additionally, three bioactive chemicals (decitabine, BW-B70C and gefitinib) based on the seven hubgenes were identified as therapeutic options for HCC by the CMap analysis.
Conclusions
Our study provides a novel insight into the pathogenesis and therapy of HCC from the circRNA–miRNA–mRNA network view.
Journal Article
LncRNA-SNHG16 predicts poor prognosis and promotes tumor proliferation through epigenetically silencing p21 in bladder cancer
More and more evidences have ensured the crucial functions of long non-coding RNAs (lncRNAs) in multiple tumors. It has been discovered that lncRNA-SNHG16 is involved in many tumors. Even so, it is still necessary to study SNHG16 comprehensively in bladder cancer. In terms of our study, the level of SNHG16 both in the tumor tissues and cell lines was measured and the relationship among SNHG16, clinicopathological traits and prognosis was explored. Interference assays were applied to determine the biological functions of SNHG16. It was discovered that the level of SNHG16 was evidently enhanced both in tissues and cell lines of bladder cancer. Patients with highly expressed SNHG16 suffered from poor overall survival. Multivariable Cox proportional hazards regression analysis implied that highly expressed SNHG16 could be used as an independent prognostic marker. It could be known from functional assays that silenced SNHG16 impaired cell proliferation, owing to the effects of SNHG16 on cell cycle and apoptosis. Finally, mechanism experiments revealed that SNHG16 could epigenetically silence the expression of p21. The facts above pointed out that lncRNA-SNHG16 might be quite vital for the diagnosis and development of bladder cancer, and could even become an important therapeutic target for bladder cancer.
Journal Article
Circular RNA circ_0020710 drives tumor progression and immune evasion by regulating the miR-370-3p/CXCL12 axis in melanoma
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.
Journal Article
Q-factor and wavelength adjustable ultra-perfect absorption under critical coupling through epsilon-near-zero-based absorbers
Perfect absorption with adjustable Q factor and wavelength is essential in both theory and application. To address this issue, a structure composed of an epsilon-near-zero (ENZ)- SiO
2
grating and a multilayer dielectric structure was designed. In the structure, the intrinsic loss is related to the ENZ thickness, while the external leakage depends on the grating parameters. By adjusting the ENZ film thickness, the intrinsic loss rate was tuned to match the external leakage rate corresponding to different grating parameters, realizing the critical couplings with different Q factors and wavelengths. Under critical coupling, the absorption rate reached a maximum of 99.999%, demonstrating ultra-perfect absorption. The Q factor was adjusted from 4350 to 35800, and the absorption wavelength was modified from 1050 to 1282 nm. The design work may provide new ideas for developing wavelength- and Q-selective absorbers, optical modulators, dielectric sensors, and photodetectors.
Journal Article
Attributing Historical and Future Evolution of Radiative Feedbacks to Regional Warming Patterns using a Green’s Function Approach
Global radiative feedbacks have been found to vary in global climate model (GCM) simulations. Atmospheric GCMs (AGCMs) driven with historical patterns of sea surface temperatures (SSTs) and sea ice concentrations produce radiative feedbacks that trend toward more negative values, implying low climate sensitivity, over recent decades. Freely evolving coupled GCMs driven by increasing CO₂ produce radiative feedbacks that trend toward more positive values, implying increasing climate sensitivity, in the future. While this time variation in feedbacks has been linked to evolving SST patterns, the role of particular regions has not been quantified. Here, a Green’s function is derived from a suite of simulations within an AGCM (NCAR’s CAM4), allowing an attribution of global feedback changes to surface warming in each region. The results highlight the radiative response to surface warming in ascent regions of the western tropical Pacific as the dominant control on global radiative feedback changes. Historical warming from the 1950s to 2000s preferentially occurred in the western Pacific, yielding a strong global outgoing radiative response at the top of the atmosphere (TOA) and thus a strongly negative global feedback. Long-term warming in coupled GCMs occurs preferentially in tropical descent regions and in high latitudes, where surface warming yields small global TOA radiation change but large global surface air temperature change, and thus a less-negative global feedback. These results illuminate the importance of determining mechanisms of warm pool warming for understanding how feedbacks have varied historically and will evolve in the future.
Journal Article
Comparative genomic investigation of high-elevation adaptation in ectothermic snakes
Several previous genomic studies have focused on adaptation to high elevations, but these investigations have been largely limited to endotherms. Snakes of the genus Thermophis are endemic to the Tibetan plateau and therefore present an opportunity to study high-elevation adaptations in ectotherms. Here, we report the de novo assembly of the genome of a Tibetan hot-spring snake (Thermophis baileyi) and then compare its genome to the genomes of the other two species of Thermophis, as well as to the genomes of two related species of snakes that occur at lower elevations. We identify 308 putative genes that appear to be under positive selection in Thermophis. We also identified genes with shared amino acid replacements in the high-elevation hot-spring snakes compared with snakes and lizards that live at low elevations, including the genes for proteins involved in DNA damage repair (FEN1) and response to hypoxia (EPAS1). Functional assays of the FEN1 alleles reveal that the Thermophis allele is more stable under UV radiation than is the ancestral allele found in low-elevation lizards and snakes. Functional assays of EPAS1 alleles suggest that the Thermophis protein has lower transactivation activity than the low-elevation forms. Our analysis identifies some convergent genetic mechanisms in high-elevation adaptation between endotherms (based on studies of mammals) and ectotherms (based on our studies of Thermophis).
Journal Article
Association between frailty and frailty change with chronic lung disease: results from two prospective cohort studies
Background
The relationship between frailty and frailty change with the risk of chronic lung disease (CLD) among middle-aged and older adults remains unclear. This study explored the associations of frailty and frailty change with CLD based on two prospective cohort studies.
Methods
The data were drawn from the Health and Retirement Study (HRS) and the China Health and Retirement Longitudinal Study (CHARLS). Frailty status was evaluated by the frailty index (FI) and categorized as robust, pre-frail, and frail. FI change was calculated as the difference between the two repeated measurements of FI, and divided into stable FI, gained FI, and decreased FI. Group-based trajectory modeling was adopted to identify the trajectory of FI. Logistic regression models were then performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI) between frailty status, frailty trajectory, and frailty change with the risk of CLD.
Results
A total of 9,178 participants from CHARLS and 11,262 participants from HRS were included. In the full-adjustment model, frail participants had higher risks of CLD compared to robust participants (CHARLS: OR = 2.28, 95% CI = 1.71–3.04; HRS: OR = 2.21, 95% CI = 1.17–4.17). The significantly elevated risks of CLD were also observed in the participants with the high-FI trajectory (CHARLS: OR = 2.11, 95% CI = 1.37–3.26; HRS: OR = 2.15, 95% CI = 1.16–3.97). The participants with decreased FI were at lower risks of CLD in the HRS (OR = 0.58, 95% CI = 0.38–0.87). However, gained FI was related to higher risks of CLD in the CHARLS (OR = 1.38, 95% CI = 1.11–1.72).
Conclusion
Frail individuals might be related with higher risks of CLD. Moreover, the progression of frailty increased the risk of CLD, while recovery of frailty decreased the risk of CLD. Appropriate interventions aimed at reversion of frailty status may be needed to prevent CLD in current clinical respiratory care.
Journal Article
Aggravation of reactive nitrogen flow driven by human production and consumption in Guangzhou City China
Human activities reshape the global nitrogen (N) cycle and affect environment and human health through reactive nitrogen (Nr) loss during production and consumption. In urbanized regions, the N cycle is greatly mediated by complex interactions between human and natural factors. However, the variations in sources, magnitude, spatiotemporal patterns and drivers of Nr flows remain unclear. Here we show by model simulations, anthropogenic perturbations not only intensify Nr input to sustain increasing demands for production and consumption in Guangzhou city, China, but also greatly change the Nr distribution pattern in the urban system, showing a substantial Nr enrichment in the atmosphere and a relatively low retention capacity of Nr in the terrestrial system. Our results highlight the strong anthropogenic effect of urban systems on the N cycle to suggest sustainable human activity changes to harmonize the relationship between Nr behaviors and human drivers.
There lacks research to figure out the variations in sources, magnitude, and spatiotemporal patterns of Nr flows in urban system. Here the authors develop a coupled human-natural urban nitrogen flow analysis model and show that anthropogenic perturbations not only intensify Nr input to sustain increasing demands for production and consumption of cities, but also greatly change the Nr distribution pattern in the urban system.
Journal Article
Serum electrolyte concentrations and risk of atrial fibrillation: an observational and mendelian randomization study
Background
Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear.
Methods
A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association.
Results
In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively.
Conclusions
Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.
Journal Article