Background/Aims: This study aims to identify whether Urothelial Cancer Associated 1 (UCA1) regulates mitochondrial metabolic reprogramming in bladder cancer, and to explore how UCA1 participates in ...mitochondrial metabolism by the UCA1/miR-195/ARL2 signaling pathway; these findings may be aid in the development of tumor diagnostic and therapeutic strategies. Methods: Bladder tissues were obtained from patients. Stable cell lines were constructed, with ectopic expression of UCA1 in UMUC2 cells and knockdown of UCA1 in 5637 cells. The expression levels of UCA1, miR-195, and ARL2 were detected by real-time PCR, western blotting, and immunohistochemistry Cell viability was detected by Cell Counting Kit-8 (CCK8) assay; mitochondrial DNA copy numbers were tested by realtime PCR; ATP level was evaluated by ATP assay kit; mitochondrial membrane potential was analyzed by 5,5’,6,6’-tetrachloro-1,1’,3,3’- tetraethylbenzimidazolylcarbocyanine iodide (JC-1) fluorescent probe. miRNAs between UCA1 and ARL2 were predicted by TargetScan and RNAHybrid, and then determined by real-time PCR. Dual-luciferase activity assay and RNA immunoprecipitation (RIP) assay were used to verify the relationship between UCA1 and miR-195. The expression level of ARL2 was silenced by small interfering RNA(siRNA). For in vivo experiments, UCA1-silencing 5637 cells were subcutaneously injected into BALB/C nude mice to evaluate the effects of UCA1 on tumor progression by the regulation of miR-195 and ARL2. Results: We demonstrate here that UCA1 enhances mitochondrial function in bladder cancer cells. UCA1 contributes to ARL2-induced mitochondrial activity, which plays an important role in mitochondrial function. UCA1, as a competing endogenous RNA (ceRNA), regulates mitochondrial function through upregulating ARL2. In this way, it inhibited the miR-195 signaling pathway to enhance mitochondrial function in bladder cancer. Additionally, ARL2 is a direct target of miR-195 and can be repressed by either miR-195 overexpression or UCA1 inhibition. Knockdown of ARL2 was analogous to the inhibition of UCA1 and the upregulation of miR-195. Animal experiments further indicated that UCA1 promoted bladder tumor growth by regulating miR-195 /ARL2. Conclusion: These data suggest that UCA1 enhanced mitochondrial function and cell viability through the UCA1/miR-195/ARL2 axis in vitro and in vivo. The elucidation of this signaling network provides a more adequate theoretical basis for understanding the molecular pathology of bladder cancer, and also UCA1 as a potential diagnosis and treatment target for bladder cancer.
Recent developments in degradation modeling have been targeted towards utilizing degradation-based sensory signals to predict residual life distributions. Typically, these models consist of ...stochastic parameters that are estimated with the aid of an historical database of degradation signals. In many applications, building a degradation database, where components are run-to-failure, may be very expensive and time consuming, as in the case of generators or jet engines. The degradation modeling framework presented herein addresses this challenge by utilizing failure time data, which are easier to obtain, and readily available (relative to sensor-based degradation signals) from historical maintenance/repair records. Failure time values are first fitted to a Bernstein distribution whose parameters are then used to estimate the prior distributions of the stochastic parameters of an initial degradation model. Once a complete realization of a degradation signal is observed, the assumptions of the initial degradation model are revised and improved for future predictions. This approach is validated using real world vibration-based degradation information from a rotating machinery application.
This paper presents a degradation modeling framework for computing condition-based residual life distributions of partially degraded systems and/or components functioning under time-varying ...environmental and/or operational conditions. Our approach is to mathematically model degradation-based signals from a population of components using stochastic models that combine three main sources of information: real-time degradation characteristics of component obtained by observing the component's in-situ degradation signal, the degradation characteristics of the component's population, and the real-time status of the environmental conditions under which the component is operating. Prior degradation information is used to estimate the model coefficients. The resulting generalized stochastic degradation model is then used to predict an initial residual life distribution for the component being monitored. In-situ degradation signals, along with real-time information related to the environmental conditions, are then used to update the residual life distributions in real-time. Because these updated distributions capture current health information and the latest environmental conditions, they provide precise lifetime estimates. The performance of the proposed models is evaluated using real world vibration-based degradation signals from a rotating machinery application.
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•Key strategies for improving electrochemical properties of NiCo2S4-based electrodes are proposed.•This work provides one specific perspective for the development of NiCo2S4-based ...composites used in energy storage devices.•This work is helpful to researchers around the world who are working on the synthesis and application of nanostructure TMSs.
NiCo2S4 has received wide attention as a promising electrode material for supercapacitors (SCs), Li-ion batteries (LIBs), and Na-ion batteries (SIBs) in the past few years because of its excellent mechanical property, low cost, and rich redox chemistry. In addition, NiCo2S4 has higher electronic conductivity than the corresponding nickel cobaltite oxide (NiCo2O4) and higher redox ability than the corresponding single-phase sulfide. Nevertheless, the actual applications of pristine NiCo2S4 without unique morphology have been restrained on account of the small specific surface area, agglomeration, and big volume change during cycling, resulting in low reversible specific capacity (capacitance) and poor cycle stability at high rates. Constructing NiCo2S4 with novel nanostructures and heterogeneous core-shell structures have been considered as one of the most promising strategy to solve these problems. In the present review, the recent research developments in the electrochemical reaction mechanisms, preparation methods, morphology control, and electrochemical property of NiCo2S4-based composites as electrode materials for SCs and secondary batteries are summarized. The main focus is to discuss the dominant factors affecting the electrochemical properties of NiCo2S4-based materials, and then highlight hopeful strategies to improve specific capacitances/capacities and cycling stability, especially at high current densities. Finally, several insights into the future developments, challenges, and prospects of NiCo2S4-based composites for SCs, LIBs, and SIBs are proposed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Layilin (LAYN) is a critical gene that regulates T cell function. However, the correlations of LAYN to prognosis and tumor-infiltrating lymphocytes in different cancers remain unclear.
LAYN ...expression was analyzed via the Oncomine database and Tumor Immune Estimation Resource (TIMER) site. We evaluated the influence of LAYN on clinical prognosis using Kaplan-Meier plotter, the PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). The correlations between LAYN and cancer immune infiltrates was investigated via TIMER. In addition, correlations between LAYN expression and gene marker sets of immune infiltrates were analyzed by TIMER and GEPIA.
A cohort (GSE17536) of colorectal cancer patients showed that high LAYN expression was associated with poorer overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). In addition, high LAYN expression was significantly correlated with poor OS and progression-free survival (PFS) in gastric cancers (OS HR = 1.97,
= 3.6e-10; PFS HR = 2.12,
= 2.3e-10). Moreover, LAYN significantly impacts the prognosis of diverse cancers via The Cancer Genome Atlas (TCGA). Specifically, high LAYN expression was correlated with worse OS and PFS in stage 2 to 4 but not stage 1 and stage N0 gastric cancer patients (
= 0.28, 0.34;
= 0.073, 0.092). LAYN expression was positively correlated with infiltrating levels of CD4+ T and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in colon adenocarcinoma (COAD) and stomach adenocarcinoma (STAD). LAYN expression showed strong correlations with diverse immune marker sets in COAD and STAD.
These findings suggest that LAYN is correlated with prognosis and immune infiltrating levels of, including those of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in multiple cancers, especially in colon and gastric cancer patients. In addition, LAYN expression potentially contributes to regulation of tumor-associated macrophages (TAMs), DCs, T cell exhaustion and Tregs in colon and gastric cancer. These findings suggest that LAYN can be used as a prognostic biomarker for determining prognosis and immune infiltration in gastric and colon cancers.
•The largest eigenvalue of the weighted adjacency matrix measures network connectivity.•Adding a link always increases the largest eigenvalue of the adjacency matrix.•A max-min integer optimization ...model is proposed to maximize the largest eigenvalue.•Results for the world container shipping network are presented.•First to use the eigenvector centrality to improve shipping network connectivity.
Container shipping accounts for most of the world merchandise trade. Better maritime connectivity leads to lower freight rates and greater economic growth. This paper presents a novel max–min integer optimization model to facilitate better shipping network connectivity by analysing the largest eigenvalue and its corresponding eigenvector of the (asymmetric) frequency weighted adjacency matrix. An algorithm is presented that can quickly identify which link not currently in the container shipping network would best improve its connectivity. A demand matrix is not required by this method of analysis and network symmetry is not assumed. The method could strengthen direct connection between port pairs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Both aberrant alternative splicing and m6A methylation play complicated roles in the development of pancreatic cancer (PC), while the relationship between these two RNA modifications remains unclear.
...RNA sequencing (RNA-seq) was performed using 15 pairs of pancreatic ductal adenocarcinoma (PDAC) tissues and corresponding normal tissues, and Cdc2-like kinases 1 (CLK1) was identified as a significantly upregulated alternative splicing related gene. Real-time quantitative PCR (qPCR) and western blotting were applied to determine the CLK1 levels. The prognostic value of CLK1 was elucidated by Immunohistochemistry (IHC) analyses in two independent PDAC cohorts. The functional characterizations and mechanistic insights of CLK1 in PDAC growth and metastasis were evaluated with PDAC cell lines and nude mice. SR-like splicing factors5
(SRSF5
) was identified as an important target phosphorylation site by phosphorylation mass spectrometry. Through transcriptome sequencing, Methyltransferase-like 14
(METTL14
) and Cyclin L2
skipping were identified as key alternative splicing events regulated by the CLK1-SRSF5 axis. RIP assays, RNA-pulldown and CLIP-qPCR were performed to confirm molecular interactions and the precise binding sites. The roles of the shift of METTL14
and Cyclin L2
skipping were surveyed.
CLK1 expression was significantly increased in PDAC tissues at both the mRNA and protein levels. High CLK1 expression was associated with poor prognosis. Elevated CLK1 expression promoted growth and metastasis of PC cells in vitro and in vivo. Mechanistically, CLK1 enhanced phosphorylation on SRSF5
, which inhibited METTL14
skipping while promoted Cyclin L2
skipping. In addition, aberrant METTL14
skipping enhanced the N6-methyladenosine modification level and metastasis, while aberrant Cyclin L2
promoted proliferation of PDAC cells.
The CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2, which promotes growth and metastasis and regulates m6A methylation of PDAC cells. This study suggests the potential prognostic value and therapeutic targeting of this pathway in PDAC patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
As one kind of novel noncoding RNA, circular RNAs (circRNAs) are involved in different biological processes. Although growing evidences have supported the important role of circRNAs in renal ...diseases, the mechanism remains unclear in neonatal acute kidney injury (AKI). High‐throughput sequencing analysis was used to investigate the expression of circRNAs between hypoxia‐induced AKI neonates and controls. Bioinformatics analysis was conducted to predict the function of differentially expressed circRNAs. Finally, the differentially expressed circRNAs were screened and determined by quantitative real‐time PCR (qPCR). (1) A total of 296 differentially expressed circRNAs were identified (Fold change >2 and p < 0.05). Of them, 184 circRNAs were markedly upregulated, and 112 were significantly downregulated in the AKI group. (2) The pathway analysis showed that ubiquitin‐mediated proteolysis, renal cell carcinoma, Jak‐STAT, and HIF‐1 signaling pathways participated in AKI. (3) Top five upregulated and five downregulated circRNAs with higher fold changes were selected for qPCR validation. Hsa_circ_0008898 (Fold Change = 5.48, p = 0.0376) and hsa_circ_0005519 (Fold Change = 4.65, p = 0.0071) were significantly upregulated, while hsa_circ_0132279 (Fold Change = −4.47, p = 0.0008), hsa_circ_0112327 (Fold Change = −4.26, p = 0.0048), and hsa_circ_0017647 (Fold Change = −4.15, p = 0.0313) were significantly downregulated in asphyxia‐induced AKI group compared with the control group. This study could contribute to future research on neonatal AKI and facilitate the identification of novel therapeutic targets.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Against a background of an environmental and resources crisis, the exploitation of renewable and clean energy can effectively alleviate the energy crisis and contribute to emission reduction and ...environmental protection, thus promoting sustainable development. This study aims to develop a grade classification map of the global ocean wind energy resource based on CCMP (cross-calibrated, multi-platform) wind field data for the period 1988–2011. We also calculate, for the first time, the total storage and effective storage of wind energy across the global ocean on a 0.25°×0.25° grid. An optimistic increasing long-term trend in wind power density was found. In addition, the global ocean wind energy resource was analyzed and regionalized by considering the temporal and spatial distributions of wind power density, wind energy levels, and effective wind speed, as well as through a consideration of wind energy storage and the stability and long-term trends of wind power density. This research fills a gap in our knowledge in this field, and provides a reference point for future scientific research and development into wind energy resources such as wind power generation, water pumping, and wind-heating.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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