Bioinformatics analysis of markers based on m6A related to prognosis combined with immune invasion of rectal adenocarcinoma.

BACKGROUND: Colorectal cancer (CRC) is a common form of cancer, with rectal cancer accounting for approximately one-third of all cases. Among rectal cancers, 95% are classified as rectal adenocarcinoma (READ). Emerging evidence suggests that long noncoding RNAs (lncRNAs) play a significant role in the development and progression of various cancers. In our study, we aimed to identify differentially expressed lncRNAs potentially associated with m6A and establish a risk assessment model to predict clinical outcomes for READ patients. METHODS: The READ dataset from the TCGA database was utilized in this study to synergistically and logically integrate m6A and lncRNA, while employing bioinformatics technology for the identification of suitable biomarkers. A risk prediction model comprising m6A-associated lncRNAs was constructed to investigate the prognostic, diagnostic, and biological functional relevance of these m6A-related lncRNAs. RESULTS: Our research builds a composed of three related to m6A lncRNA rectal gland cancer prognosis model, and the model has been proved in the multi-dimensional can serve as the potential of the prognosis of rectal gland cancer biomarkers. Our study constructed a prognostic model of rectal adenocarcinoma consisting of three related m6A lncRNAs: linc00702, ac106900.1 and al583785.1. CONCLUSION: The model has been validated as a potential prognostic biomarker for rectal cancer in multiple dimensions, aiming to provide clinicians with an indicator to assess the duration of straight adenocarcinoma. This enables early detection of rectal cancer and offers a promising target for immunotherapy.

Hsa_circRNA_102051 regulates colorectal cancer proliferation and metastasis by mediating Notch pathway.

BACKGROUND: The purpose of this study was to investigate the role of hsa_circRNA_102051 in colorectal cancer (CRC) and its effect on the stemness of tumor cells. METHODS: CircRNA microarray was under analysis to screen differentially expressed novel circRNAs in the pathology of CRC. Quantitative real-time PCR was used to detect the relative RNA expression in CRC cells and samples. The effects of hsa_circRNA_102051 on biological functions in CRC cells were accessed both in vitro and in vivo. FISH, RIP and luciferase reporter assay were conducted to confirm the regulatory correlations between hsa_circRNA_102051 and miR-203a, as well as miR-203a and BPTF. Xenograft models were applied to further verify the impacts and fluctuations of hsa_circRNA_102051/miR-203a/BPTF. Moreover, the mechanism how hsa_circRNA_102051 affected the Notch signals was also elucidated. RESULTS: Hsa_circRNA_102051 was up-regulated in CRC tissues and cell lines, capable to promote the growth and invasion of CRC. In addition, hsa_circRNA_102051 could enhance stemness of CRC cells. BPTF was identified as downstream factors of hsa_circRNA_102051, and miR-203a was determined directly targeting both hsa_circRNA_102051 and BPTF as an intermediate regulator. Hsa_circRNA_102051 in CRC could block miR-203a expression, and subsequently activated BPTF. Hsa_circRNA_102051/miR-203a/BPTF axis modulated stemness of CRC cells by affecting Notch pathway. CONCLUSIONS: Our findings provided new clues that hsa_circRNA_102051 might be a potential predictive or prognostic factor in CRC, which induced the fluctuation of downstream miR-203a/BPTF, and subsequently influenced tumor growth, activities and stemness. Thereinto, the Notch signals were also involved. Hence, the hsa_circRNA_102051/miR-203a/BPTF axis could be further explored as a therapeutic target for anti-metastatic therapy in CRC patients.

High-quality reconstruction of China's natural streamflow.

Reconstruction of natural streamflow is fundamental to the sustainable management of water resources. In China, previous reconstructions from sparse and poor-quality gauge measurements have led to large biases in simulation of the interannual and seasonal variability of natural flows. Here we use a well-trained and tested land surface model coupled to a routing model with flow direction correction to reconstruct the first high-quality gauge-based natural streamflow dataset for China, covering all its 330 catchments during the period from 1961 to 2018. A stronger positive linear relationship holds between upstream routing cells and drainage areas, after flow direction correction to 330 catchments. We also introduce a parameter-uncertainty analysis framework including sensitivity analysis, optimization, and regionalization, which further minimizes biases between modeled and inferred natural streamflow from natural or near-natural gauges. The resulting behavior of the natural hydrological system is represented properly by the model which achieves high skill metric values of the monthly streamflow, with about 83% of the 330 catchments having Nash-Sutcliffe efficiency coefficient (NSE) > 0.7, and about 56% of the 330 catchments having Kling-Gupta efficiency coefficient (KGE) > 0.7. The proposed construction scheme has important implications for similar simulation studies in other regions, and the developed low bias long-term national datasets by statistical postprocessing should be useful in supporting river management activities in China.

Efficacy and safety of blood derivatives therapy in Alzheimer's disease: a systematic review and meta-analysis.

BACKGROUND: Blood derivatives therapy is a conventional clinical treatment, while the treatment for Alzheimer's disease (AD) is relatively novel. To provide clinical references for treating AD, this meta-analysis was performed to evaluate the efficacy and safety of blood derivatives therapy on the patients with AD. METHODS: A systematic articles search was performed for eligible studies published up to December 6, 2021 through the PubMed, Embase, Cochrane library, ClinicalTrials.gov , Chinese National Knowledge Infrastructure database, and Wanfang databases. The included articles were screened by using rigorous inclusion and exclusion criteria. Study selection and data-extraction were performed by two authors independently. Random effects model or fixed effects model was used. Quality of studies and risk of bias were evaluated according to the Cochrane risk of bias tool. All analyses were conducted using Review Manager 5.4. The study was designed and conducted according to the Preferring Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. RESULTS: A total of three plasma administrations (two plasma exchange and one young plasma infusion) and five intravenous immunoglobulin (IVIG) randomized controlled trials with a sample size of 1148 subjects diagnosed with AD were included. There was no significant difference in cognitive improvement and all-cause discontinuation between intervention and placebo groups (RR 1.10, 95% CI 0.79-1.54). And Intervention groups showed not a statistically significant improvement in cognition of included subjects measured by the ADAS-Cog (MD 0.36, 95% CI 0.87-1.59), ADCS-ADL (MD -1.34, 95% CI - 5.01-2.32) and NPI (MD 2.20, 95% CI 0.07-4.32) score compared to the control groups. IVIG is well tolerated for AD patients even under the maximum dose (0.4 g/kg), but it is inferior to placebo in Neuropsychiatric Inventory scale in AD patients (MD 2.19, 95% CI 0.02-4.37). CONCLUSIONS: The benefits of blood derivatives therapy for AD are limited. It is necessary to perform well-designed randomized controlled trials with large sample sizes focusing on the appropriate blood derivatives for the specific AD sub-populations in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021233886.

Efficacy and Safety of Blood Derivative Therapy for Patients with COVID-19: A Systematic Review and Meta-Analysis.

Background: The outbreak of COVID-19 has resulted in more than 200 million infections and 4 million deaths. The blood derivative therapy represented by intravenous immunoglobulin (IVIG) and convalescent plasma (CP) therapy may be the promising therapeutics for COVID-19. Methods: A systematic article search was performed for eligible studies published up to August 3, 2021, through the PubMed, Embase, Cochrane Library. The included articles were screened by using rigorous inclusion and exclusion criteria. All analyses were conducted using Review Manager 5.4. Quality of studies and risk of bias were evaluated. Results: A total of 5 IVIG therapy and 13 CP therapy randomized controlled trials were included with a sample size of 13,696 subjects diagnosed with COVID-19. IVIG could reduce the mortality compared with the control group (RR 0.65, 95% CI: 0.46-0.93, p = 0.02). The use of CP did not effectively reduce the mortality (RR 0.97, 95% CI: 0.91-1.03, p = 0.38), the length of hospital stay (MD -0.47, 95% CI: -4.13 to 3.20, p = 0.80), and the mechanical ventilation use (RR = 0.98, 95% CI: 0.89-1.07, p = 0.62) of the patients with COVID-19. Treatment with IVIG or CP was not significantly associated with an increase in reported adverse events (RR 1.07, 95% CI: 0.94-1.22, p = 0.28). Conclusions: Treatment with IVIG could be effective and safe to improve survival for patients with COVID-19. But the benefit of CP in the treatment of COVID-19 is limited. The certainty of the evidence was moderate for all outcomes.

The effects of terrain factors on the drainage area threshold: comparison of principal component analysis and correlation analysis.

How and to which extent terrain factors affecting the drainage area threshold (DAT) are disputable. This paper uses principal component analysis (PCA) and correlation analysis to study the influence degree of terrain factors on DAT. Firstly, 22 watersheds, locating in the severe soil erosion region (SSER) of Loess Plateau of China, are picked out as the example areas. The purpose of the mean change point method (MCP) to detect the relationship between DAT and gully density (GD) is to get a reasonable DAT. Secondly, nine terrain factors are calculated, and their statistical values are compared and put in the matrix to clear the different effects on DAT. Finally, the effects of statistical eigenvalues of terrain factors on DAT are compared with PCA and the correlation analysis. According to the PCA, the nine terrain factors are summarized into three principal components, which are slope, height variation, and relief factor. By calculating the score weighted by each factor coefficient matrix and eigenvalue, the result states that slope (S), terrain curvatures (K), and surface roughness (SR) are the factors that have great influence on DAT. Meanwhile, the results of correlation analysis indicate that S, SR, and K have exerted a great influence on the DAT, and the significance level was above 0.05. Both the results of PCA and correlation analysis make clear that the slope is the most direct and influential factor affecting DAT, while other factors are more or less related to slope directly and indirectly. The result implies that the vertical variation of terrain has a strong correlation with the slope, and also has a great influence on DAT. This research not only would be of great significance to recognize the mechanism of gully development, but also able to provide a scientific reference for soil and water conservation in the Loess Plateau.

In vitro Aggregation Ability of Five Commercially Available Aß42 peptide.

BACKGROUND: As the most basic material, synthetic human Amyloid-ß (1-42) (Aß42) peptide from different manufacturers have been widely used. Their aggregation ability is vital to the reliability, repeatability and comparability of studies on Aß42 physiology and pathology. However, it has not been evaluated and compared. OBJECTIVE: To analyze the consistency of the aggregation ability of 5 commercially available Aß42 peptide. METHODS: 5 Aß42 peptide represented as A, B, C, D and E were pretreated by HFIP. The pretreated Aß42 peptide were dissolved in Thioflavin T (ThT) solution, and their aggregation kinetics was monitored for 30 h with the aggregation kinetics test. Meanwhile, the pretreated peptide were aggregated in phosphate buffered saline. After aggregated for 12 h, they were detected by methods of ThT fluorescence, far-UV circular dichroism (CD), SDS-PAGE, western blot, and transmission electron microscopy (TEM), respectively. After aggregation for 8 h and 12 h, their cytotoxicity to SH-SY5Y cells was further evaluated using Cell Counting Kit-8. RESULTS: For aggregation kinetics, peptide A, C and E remained low level curves, while peptide B and D presented typical sigmoidal kinetics curves. In CD measurement, the aggregates of peptide B and D showed relatively high negative CD peaks with the height of -8.09 mdeg and -14.37 mdeg, while the height of peptide A, C and E was -1.04, -3.55, and -3.88. In ThT assay, relative fluorescence intensity of the aggregates of peptide B and D were 7.79 and 8.82, higher than 1.19, 1.71, and 2.70 of peptide A, C and E, respectively. In SDS-PAGE, all aggregates contained monomers and eleven polymers. Moreover, peptide B-E presented a trapezoidal distribution from dimers to trimers, and peptide A aggregated to dimers. By western blot, the bands of monomers remained in all aggregates. Furthermore, peptide B and D aggregated to dimers and trimers, peptide A and C only aggregated to dimers, and peptide E showed a strong band of trimers. By TEM, protofibrils were observed only in peptide B, while substantial spherical aggregates were formed in other peptide. Additionally, peptide B, D and E exhibited higher cytotoxicity after aggregated for 8 h, whereas peptide A, B and D presented relatively high cytotoxicity after 12-hour aggregation. CONCLUSION: Commercially available Aß42 peptide showed obvious differences in aggregation ability, which should arouse enough attention in the field of basic study related to Aß42. The aggregation ability evaluation with the various assay methods has some discrepancies, and it is highly urgent to establish a reasonable and uniform measurement strategy.

Revisiting the genome-wide significance threshold for common variant GWAS.

Over the last decade, GWAS meta-analyses have used a strict P-value threshold of 5 × 10-8 to classify associations as significant. Here, we use our current understanding of frequently studied traits including lipid levels, height, and BMI to revisit this genome-wide significance threshold. We compare the performance of studies using the P = 5 × 10-8 threshold in terms of true and false positive rate to other multiple testing strategies: (1) less stringent P-value thresholds, (2) controlling the FDR with the Benjamini-Hochberg and Benjamini-Yekutieli procedure, and (3) controlling the Bayesian FDR with posterior probabilities. We applied these procedures to re-analyze results from the Global Lipids and GIANT GWAS meta-analysis consortia and supported them with extensive simulation that mimics the empirical data. We observe in simulated studies with sample sizes ∼20,000 and >120,000 that relaxing the P-value threshold to 5 × 10-7 increased discovery at the cost of 18% and 8% of additional loci being false positive results, respectively. FDR and Bayesian FDR are well controlled for both sample sizes with a few exceptions that disappear under a less stringent definition of true positives and the two approaches yield similar results. Our work quantifies the value of using a relaxed P-value threshold in large studies to increase their true positive discovery but also show the excess false positive rates due to such actions in modest-sized studies. These results may guide investigators considering different thresholds in replication studies and downstream work such as gene-set enrichment or pathway analysis. Finally, we demonstrate the viability of FDR-controlling procedures in GWAS.

LncRNA EWSAT1 Promotes Colorectal Cancer Progression Through Sponging miR-326 to Modulate FBXL20 Expression.

BACKGROUND: Ewing sarcoma-associated transcript 1 (EWSAT1) has been reported to be a pivotal modulator in a series of cancers. However, the function of EWSAT1 in colorectal cancer (CRC) has not been elaborated. This study aimed to explore the role of EWSAT1 in CRC progression and the underlying mechanisms. METHODS: The expression patterns of EWSAT1, miR-326 and FBXL20 were examined by qCRCR. Si-EWSAT1 was transfected to study the effects of EWSAT1 on cell proliferation and metastasis. Rescue experiments were performed to investigate the underlying mechanisms in vitro. Xenograft models were used to evaluate the role of EWSAT1 in vivo. RESULTS: We found that EWSAT1 was highly expressed in CRC tissues and cell lines and associated with poor overall survival. In vitro, knockdown of EWSAT1 suppressed the cell proliferation, migration and invasion. Moreover, miR-326 was found to be a target of EWSAT1, and miR-326 inhibitor could partially reverse the effects on CRC cell progression induced by si-EWSAT1. Subsequently, we validated FBXL20 as a vital downstream target for miR-326, and EWSAT1 positively regulated FBXL20 via miR-326 in vitro. In addition, these findings were confirmed by in vivo experiments. CONCLUSION: Taken together, the data showed that EWSAT1 promoted CRC progression via targeting miR-326/FBXL20 pathway, which might provide a novel therapeutic target for CRC treatment.

Multidimensional evaluation of the TRMM 3B43V7 satellite-based precipitation product in mainland China from 1998-2016.

This study evaluates the applicability of the Tropical Rain Measurement Mission (TRMM) 3B43V7 product for use throughout mainland China. Four statistical metrics were used based on the observations made by rain gauges; these metrics were the correlation coefficient (R), the relative bias (RB), the root mean square error (RMSE) and Nash-Sutcliffe efficiency (NSE), and they were chosen to evaluate the performance of the 3B43V7 product at temporal and spatial scales. The results revealed that 3B43V7 performed satisfactorily on all timescales (R > 0.9 and NSE > 0.86); however, it overestimated the results when compared with the rain gauge observations in certain circumstances (RB = 9.7%). Monthly estimates from 3B43V7 were in agreement with rain gauge observations. 3B43V7 can effectively capture the seasonal patterns of precipitation characteristics over mainland China. However, 3B43V7 tends to register a greater overestimation of precipitation in the winter (RB = 14%) than in other seasons while showing greater consistency with the observations made by rain gauges during dry periods. The 3B43V7 product performs well in the eastern part of mainland China, while its performance is poor in the western part of mainland China. In terms of altitude, 3B43V7 performs satisfactorily in areas with moderate to low altitudes (when altitude < 3,500 m, R > 0.9, NSE > 0.8 and RB < 10.2%) but RB values increase with altitude. Overall, 3B43V7 had a favorable performance throughout mainland China.

Self-cleaning isotype g-C3N4 heterojunction for efficient photocatalytic reduction of hexavalent uranium under visible light.

Photocatalysis is a promising method to eliminate hexavalent uranium (U(Ⅵ)) and recycle it from wastewater. However, most of researched photocatalysts are metal-contained, inactive in visible light, and inconvenient to recycle, which unfortunately impedes the further utilization of photocatalytic technology in U(Ⅵ) pollution treatment. Herein, g-C3N4 isotype heterojunction with interpenetrated tri-s-triazine structure (ipCN) was prepared by inserting urea into the interlayer of tri-s-triazine planes of thiourea-derived g-C3N4 and in-site thermal treating. The synthesized nanocomposites were used to convert soluble U(Ⅵ) ions into U(Ⅳ) sediment under visible light. Experimental and characterization results reveal that ipCN possess larger BET surface area, more negative-charged surface, higher U(Ⅵ) adsorption capability, and more efficient mass diffusion and charges transfer properties. With these excellent characteristics, nearly 98% U(Ⅵ) could be removed within 20 min over ipCN5:1 and 92% photoreduction efficiency could also be kept after 7 cycle uses, which were equal to or even superior than most reported metal-based photocatalysts. It is also proven that the configuration of U(Ⅵ) and photogenerated ·O2- play a significant role in the photocatalytic U(Ⅵ) reduction process, with (UO2)x(OH)y2x-y are more prone to be adsorbed and the photoinduced process of ·O2- will steal electrons from photocatalysts. Furthermore, with the self-generated ·O2- and H2O2, a green and facile regeneration process of photocatalysts was proposed This work provides a promising scheme to extract U(Ⅵ) from the perspectives of photocatalysts exploitation, photocatalytic reduction, and photocatalysts regeneration, which is meaningful for the sustainable U(Ⅵ) resource recovery and U(Ⅵ) pollution purification.

LINC00858 promotes colorectal cancer by sponging miR-4766-5p to regulate PAK2.

OBJECTIVES: LncRNAs (long noncoding RNAs) have been reported to critically regulate colorectal cancer (CRC). We prospectively investigated effects and mechanisms of lncRNA LINC00858 on regulation of CRC progression. METHODS: Expression of LINC00858 and its target were analyzed by quantitative real-time polymerase chain reaction and in situ hybridization. MTT and bromodeoxyuridine/5-bromo-2'-deoxyuridine (BrdU) staining to assess cell proliferation ability. Flow cytometry, wound healing, and transwell assays were conducted to evaluate cell apoptosis, migration, and invasion, respectively. Interaction between LINC00858 and its target was confirmed by luciferase activity assay and RNA immunoprecipitation. Subcutaneous xenotransplanted tumor model was established and employed to detect tumorigenic functions of LINC00858, and further evaluated by qRT-PCR, western blot, immunohistochemistry, and hematoxylin and eosin staining. RESULTS: With a predicted poor prognosis, LINC00858 was upregulated in CRC patients. LINC00858 knockdown suppressed cell proliferation, invasion, and migration abilities, meanwhile induced cell apoptosis. Moreover, LINC00858 could target and inhibit the miR-4766-5p expression, thus promoting CRC progression. miR-4766-5p further suppressed serine/threonine kinase PAK2. Interestingly, interference of LINC00858 suppressed tumorigenic ability of CRC in vivo by downregulating PAK2. CONCLUSIONS: LINC00858 promoted CRC progression by sponging miR-4766 to upregulate PAK2, shedding lights on LINC00858 as a potential therapeutic target candidate in CRC treatment from bench to clinic.

Combining sequence data from multiple studies: Impact of analysis strategies on rare variant calling and association results.

Individual sequencing studies often have limited sample sizes and so limited power to detect trait associations with rare variants. A common strategy is to aggregate data from multiple studies. For studying rare variants, jointly calling all samples together is the gold standard strategy but can be difficult to implement due to privacy restrictions and computational burden. Here, we compare joint calling to the alternative of single-study calling in terms of variant detection sensitivity and genotype accuracy as a function of sequencing coverage and assess their impact on downstream association analysis. To do so, we analyze deep-coverage (~82×) exome and low-coverage (~5×) genome sequence data on 2,250 individuals from the Genetics of Type 2 Diabetes study jointly and separately within five geographic cohorts. For rare single nucleotide variants (SNVs): (a) ≥97% of discovered SNVs are found by both calling strategies; (b) nonreference concordance with a set of highly accurate genotypes is ≥99% for both calling strategies; (c) meta-analysis has similar power to joint analysis in deep-coverage sequence data but can be less powerful in low-coverage sequence data. Given similar data processing and quality control steps, we recommend single-study calling as a viable alternative to joint calling for analyzing SNVs of all minor allele frequency in deep-coverage data.

Circular RNA hsa_circRNA_103809 promoted hepatocellular carcinoma development by regulating miR-377-3p/FGFR1/ERK axis.

In the last decade, circular RNAs (circRNAs) emerge as important regulators in multiple biological processes. Lately, it is reported hsa_circRNA_103809 could play vital parts in several types of cancers. Based on the analysis of GEO data (GSE97332), hsa_circRNA_103809 was found to be dysregulated in hepatocellular carcinoma (HCC). However, the biological function and underlying regulatory mechanisms of hsa_circRNA_103809 in HCC remain unclear. Our results suggested that hsa_circRNA_103809 was overexpressed in HCC patients, and hsa_circRNA_103809 knockdown remarkably inhibited the proliferation, cycle progression, and migration of HCC cells. The investigations of molecular showed that hsa_circRNA_103809 could elevate the protein expression of a miR-377-3p target, fibroblast growth factor receptor 1 (FGFR1), through interacting with miR-377-3p and decreasing its expression level. Additionally, in vivo assays revealed hsa_circRNA_103809 short hairpin RNA served as a tumor suppressor through downregulating FGFR1 in HCC. This study systematically investigated novel regulatory signaling of hsa_circRNA_103809/miR-377-3p/FGFR1 axis, providing insights into hepatocellular carcinoma treatment from bench to clinic.

Leucine-rich Repeats and Immunoglobulin 1 (LRIG1) Ameliorates Liver Fibrosis and Hepatic Stellate Cell Activation via Inhibiting Sphingosine Kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P) Pathway.

To detect the leucine-rich repeats and immunoglobulin 1 (LRIG1) ameliorated liver fibrosis and hepatic stellate cell (HSC) activation via inhibiting sphingosine kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P) pathway. C57BL/6 male mice (eight weeks old) were intraperitoneal injection with 10% carbon tetrachloride (CCl4) as an in vivo model. The LX-2 cells were induced as amodel for in vitro study by TGF-ß (10 ng/mL). The Hematoxylin-eosin (HE) staining, Masson staining, and Sirius red staining results showed that CCl4 caused serious fibrosis and injury in liver tissue, high expression of type I collagen α1 chain (Col1α1) and α-smooth muscle actin (α-SMA) in liver tissue, while the LRIG1 expression level was significantly decreased in LX-2 cell lines. The LRIG1 ameliorated CCl4-induced liver fibrosis, indicated by the fibronectin, α-SMA, LRIG1, SphK1, Col1α1, fibrin Connexin 1 (Fn1), tissue inhibitor of metalloproteinase-1 (TIMP1), sphingosine-1-phosphate (S1P), transforming growth factor-beta 1 (TGF-ß1) expression level changes. Similar results were observed in TGF-ß1 treated of LX-2 cells. However, the effects were attenuated by treatment with LRIG1. Moreover, SphK1 inhibitors abrogated the effect of LRIG1 on fibrosis. These results demonstrated that LRIG1 improved liver fibrosis in vitro and in vivo via suppressing the SphK1/S1P pathway, indicating its potential use in the treatment of liver fibrosis.

In vitro mitochondrial-targeted antioxidant peptide induces apoptosis in cancer cells.

INTRODUCTION: Reactive oxygen species (ROS) are major contributors to cancer and involved in numerous tumor proliferation signaling pathways. Mitochondria are the major ROS-producing organelles, and ROS are produced from the synthesis of adenosine triphosphate and cell metabolism. METHODS: A novel mitochondria-targeted peptide, namely KRSH, was synthesized and characterized. KRSH consists of four amino acids; lysine and arginine contain positively charged groups that help KRSH target the mitochondria, while tyrosine and cysteine neutralize excessive endogenous ROS, thereby inhibiting tumorigenesis. RESULTS: The results indicated that KRSH is specifically inhibiting the growth of HeLa and MCF-7 cancer cell lines. However, MCF10A cells can resist the effects of KRSH even in a relative higher concentration. The dichloro-dihydro-fluorescein diacetate and MitoSOXTM Red assay suggested that KRSH drastically decreased the level of ROS in cancer cells. The mitochondrial depolarization assay indicated that treatment with KRSH at a dose of 50 nM may decrease the mitochondrial membrane potential leading to apoptosis of HeLa and MCF-7 cells. CONCLUSION: In other studies, investigating rat liver mitochondria, the uptake of KRSH may reach 80% compared with that for mitoquinone. Therefore, KRSH was designed as a superior peptide antioxidant and a mitochondria-targeting anticancer agent.

circCTIC1 promotes the self-renewal of colon TICs through BPTF-dependent c-Myc expression.

Colon tumor is a conman tumor in the world. There are various kinds of cells in colon tumor bulk, and only a small population can initiate tumor efficiently and termed as tumor-initiating cells (TICs). With self-renewal and differentiation capacities, colon TICs drive colon tumorigenesis, metastasis and relapse. However, the molecular mechanisms of colon TICs self-renewal are elusive. Here, we found that circular RNA (circCTIC1) was highly expressed in colon tumor and colon TICs. circCTIC1 knockdown impaired the self-renewal of colon TICs, and its overexpression played an opposite role. circCTIC1 promoted the expression of c-Myc and drove the self-renewal of colon TIC through c-Myc-dependent manner. circCTIC1 interacted with nuclear remodeling factor (NURF) complex, recruited NURF complex onto c-Myc promoter and finally drove the transcriptional initiation of c-Myc. Altogether, circCTIC1 drove the self-renewal of colon TICs through bromodomain PHD finger transcription factor (BPTF)-mediated c-Myc expression.

Reconstructed Order Analysis-Based Vibration Monitoring under Variable Rotation Speed by Using Multiple Blade Tip-Timing Sensors.

On-line vibration monitoring is significant for high-speed rotating blades, and blade tip-timing (BTT) is generally regarded as a promising solution. BTT methods must assume that rotating speeds are constant. This assumption is impractical, and blade damages are always formed and accumulated during variable operational conditions. Thus, how to carry out BTT vibration monitoring under variable rotation speed (VRS) is a big challenge. Angular sampling-based order analyses have been widely used for vibration signals in rotating machinery with variable speeds. However, BTT vibration signals are well under-sampled, and Shannon's sampling theorem is not satisfied so that existing order analysis methods will not work well. To overcome this problem, a reconstructed order analysis-based BTT vibration monitoring method is proposed in this paper. First, the effects of VRS on BTT vibration monitoring are analyzed, and the basic structure of angular sampling-based BTT vibration monitoring under VRS is presented. Then a band-pass sampling-based engine order (EO) reconstruction algorithm is proposed for uniform BTT sensor configuration so that few BTT sensors can be used to extract high EOs. In addition, a periodically non-uniform sampling-based EO reconstruction algorithm is proposed for non-uniform BTT sensor configuration. Next, numerical simulations are done to validate the two reconstruction algorithms. In the end, an experimental set-up is built. Both uniform and non-uniform BTT vibration signals are collected, and reconstructed order analysis are carried out. Simulation and experimental results testify that the proposed algorithms can accurately capture characteristic high EOs of synchronous and asynchronous vibrations under VRS by using few BTT sensors. The significance of this paper is to overcome the limitation of conventional BTT methods of dealing with variable blade rotating speeds.

Membrane-type smart metamaterials for multi-modal sound insulation.

Metamaterial provides a promising way to control low-frequency noise, but its narrow bandgap limits its applications. To end this, a membrane-type smart metamaterial with multi-modal sound insulation property is studied. The proposed metamaterial consists of an aluminum membrane bonded with multi-modal resonant piezoelectric resonators. Both simulated and experimental results show that the proposed metamaterial can broaden the locally resonant bandgaps because of the effect of the multi-modal resonance (the percent bandwidths are 0.19 and 0.22 for the lowest mode and higher two modes, respectively). Large multi-modal sound insulations (over 37 dB) are obtained around the designed resonant frequencies in low frequency regime (<2000 Hz) with an ultra-thin thickness (over 1000 times thinner than the acoustic wavelength). It is also demonstrated that the excellent sound insulation property can be tuned by simply adjusting the external circuits instead of modifying the structure itself. The underlying mechanism of the unusual sound insulation of the proposed metamaterial is attributed to the negative effective bending stiffness Deq derived by the effective medium method. In addition, the parametric study shows that the circuital parameters (capacitances) are inversely related to the sound transmission loss of the proposed multi-resonant metamaterial, which benefits the optimization of insulation effect.

Ionic Liquid as an Efficient Medium for the Synthesis of Quinoline Derivatives via α-Chymotrypsin-Catalyzed Friedländer Condensation.

An efficient, convenient, and eco-friendly biocatalytic approach was developed for the synthesis of quinoline derivatives via the α-chymotrypsin-catalyzed Friedländer reaction. Interestingly, α-chymotrypsin exhibited higher catalytic activity in an ionic liquid (IL) aqueous solution as compared to that observed in our previous relevant study, which was conducted using an organic solvent, and a series of substrates gave similar excellent yields at lower reaction temperature and under reduced enzyme-loading conditions.