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Permeable asphalt mixtures are widely used to achieve good permeability of the pavements used for urban road surfaces. Based on the law of water migration in permeable road structures, the water-holding performance of permeable asphalt mixtures was analyzed and the evaluation indexes were determined. Open-graded asphalt friction course (OGFC-13) permeable asphalt mixture was selected, and the changes in the saturation, water retention, and water-holding rate of OGFC-13 permeable asphalt mixtures with different porosities were compared using water-holding equipment. The water-holding characteristics of permeable pavement materials under different seepage conditions were analyzed. A model of the relationship governing the water-holding capacity of the permeable asphalt mixture, water action conditions, and material porosity was established by a linear fitting method, and the reliability of the model was verified by comparison with laboratory test results, providing a foundation for related research on the water-holding and cooling behavior of permeable pavements.

Purpose Ferulic acid (FA) is a natural compound which is used to treat insomnia. However, its use is limited because of its poor oral bioavailability caused by extremely rapid elimination. The current study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral delivery of FA and to enhance its hypnotic efficacy. Methods FA-SMEDDS was prepared, and its morphology and storage stability were characterized. The formulation was also subjected to pharmacokinetic and tissue distribution studies in rats. The hypnotic efficacy of FA-SMEDDS was evaluated in p-chlorophenylalanine-induced insomnia mice. Results FA-loaded SMEDDS exhibited a small droplet size (15.24 nm) and good stability. Oral administration of FA-SMEDDS yielded relative bioavailability of 185.96%. In the kidney, SMEDDS decreased the distribution percentage of FA from 76.1% to 59.4% and significantly reduced its metabolic conversion, indicating a reduction in renal elimination. Interestingly, FA-SMEDDS showed a higher distribution in the brain and enhanced serotonin levels in the brain, which extended the sleep time by 2-fold in insomnia mice. Conclusion This is the first study to show that FA-loaded SMEDDS decreased renal elimination, enhanced oral bioavailability, increased brain distribution, and improved hypnotic efficacy. Thus, we have demonstrated that SMEDDS is a promising carrier which can be employed to improve the oral delivery of FA and facilitate product development for the therapy of insomnia.

Background:Breast cancer (BC) is one of the most common tumors in women. Recent years, immune checkpoint inhibitors (ICIs) have brought good news to BC patients. Although significant achievements have been made through treatment with ICIs, some people who experience serious immune-related adverse events (IrAEs) are still insensitive to this approach. The response to ICI treatment depends on the type of tumor microenvironment (TME). Methods:WGCNA (weighted gene co-expression network analysis), ESTIMATE algorithm, LASSO regression analysis, survival analysis, functional enrichment analysis are conducted to analyze the BC data in the TCGA database. Immunohistochemistry was used to verify the expression of CD52 in BC.Results:WGCNA and ESTIMATE algorithm found that the CD52 is closely related to the immune microenvironment. CD52 highly expressed in various breast cancer subtypes, and patients with high expression of CD52 have longer survival time. Compared with the low-CD52 group, the high-CD52 group had more immune cell infiltration. TIMER database verification results showed that CD8+ T cells, activated memory CD4 T cells, memory B cells, γδ T cells, and Tregs were positively correlated with CD52 expression, while M2 macrophages were negatively correlated. CD52 can change the trend of TIC (CD8+ T) and tumor-associated macrophage (TAM) infiltration with respect to the survival time of breast cancer patients. Based on the expression of CD52, we explored the relationship between CD52 and the adaptive immune response (AIR). CD52 is a marker of AIR stratification in breast cancer patients. We constructed a CD52-related adaptive immune response gene signature (CD52rAIRGsig) which is an independent prognostic factor for breast cancer and related to genome instability and the immune cells infiltration in the TME. CD52 and CD52rAIRGsig were associated with PD-1 signaling and immune checkpoint inhibitor markers, which proves that patients with high CD52 expression and low risk of CD52rAIRGsig are more suitable for ICI treatment. We then screened chemotherapeutics for personalized medicine based on CD52rAIRGsig. Conclusion:Therefore, we have discovered a new marker to guide the treatment and prognosis of breast cancer patients with ICIs. This provides a combined treatment strategy including different combinations of ICIs combined with chemotherapeutic drugs to treat breast cancer.

Colon adenocarcinoma (COAD) is one of the diseases with the highest morbidity and mortality in the world. At present, immunotherapy has become a valuable method for the treatment of COAD. Tumor mutational burden (TMB) is considered to be the most common biomarker for predicting immunotherapy. According to reports, the mutation rate of COAD ranks third. However, whether these gene mutations are related to TMB and immune response is still unknown. Here, COAD somatic mutation data were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Bioinformatics methods were used to study the relationships among gene mutations, COAD survival prognosis, and tumor immune response. A total of 22 of the top 40 mutations in TCGA and ICGC databases were the same. Among them, the USH2A mutation was associated with high TMB and poor clinical prognosis. According to Gene Set Enrichment Analysis (GSEA) and the CIBERSORT algorithm, we determined that the USH2A mutation upregulates signaling pathways involved in the immune system and the antitumor immune response. In cases with a USH2A mutation, the immune score and MSI score of TCGA samples increased, the expression of immune checkpoint genes decreased significantly, and the TIDE score decreased significantly. Dependent on the presence or absence of a USH2A mutation, TCGA COAD samples were analyzed for differentially expressed genes, 522 of which were identified. Using a univariate Cox analysis and LASSO COX analysis of these differential genes, a prediction model was established, which established significant differences in the infiltration of immune cells, immune checkpoint gene expression, immune score, MSI score, TMB, and TIDE in patients in high- and low-risk groups. In conclusion, mutation of USH2A is frequent in COAD and is related to an increase in TMB and the antitumor immunity. The differential genes screened by USH2A mutation allowed the construction of a risk model for predicting the survival and prognosis of cancer patients, in addition to providing new ideas for COAD immunotherapy.

Long non-coding RNA (lncRNA) is a prognostic biomarker for many types of cancer. Here, we aimed to study the prognostic value of lncRNA in Breast Invasive Carcinoma (BRCA). We downloaded expression profiles from The Cancer Genome Atlas (TCGA) datasets. Subsequently, we screened the differentially expressed genes between normal tissues and tumor tissues. Univariate Cox, LASSO regression, and multivariate Cox regression analysis were used to construct a lncRNA prognostic model. Finally, a nomogram based on the lncRNAs model was developed, and weighted gene co-expression network analysis (WGCNA) was used to predict mRNAs related to the model, and to perform function and pathway enrichment. We constructed a 6-lncRNA prognostic model. Univariate and multivariate Cox regression analysis showed that the 6-lncRNA model could be used as an independent prognostic factor for BRCA patients. We developed a nomogram based on the lncRNAs model and age, and showed good performance in predicting the survival rates of BRCA patients. Also, functional pathway enrichment analysis showed that genes related to the model were enriched in cell cycle-related pathways. Tumor immune infiltration analysis showed that the types of immune cells and their expression levels in the high-risk group were significantly different from those in the low-risk group. In general, the 6-lncRNA prognostic model and nomogram could be used as a practical and reliable prognostic tool for invasive breast cancer.

There is increasing appreciation for the roles of the gut-liver axis in liver and gall diseases. Specific gut microbes are associated with susceptibility to gallstone diseases, while the relationship between intestinal flora and liver metabolism in the formation of gallstones remains unclear. In this study, an experimental group of model mice was given a lithogenic diet, and a control group was given a normal diet. Both groups were fed for 8 weeks. Integrating 16S rRNA gene sequencing and non-targeted metabolomics to explore the impact of the lithogenic diet on intestinal flora and liver metabolism, Spearman correlation analysis reveals the network of relationships between the intestine and liver. Our findings showed that the gut microbiome and liver metabolome compositions of the test group were significantly changed compared with those of the normal group. Through our research, biomarkers of gallstones were identified at the phylum (5), class (5), order (5), family (7), and genus levels. We predicted the function of the differential flora. We analyzed the liver metabolism of mice with gallstones paired with their flora, and the results showed that there were 138 different metabolites between the two groups. The metabolic pathways enriched by these differential metabolites are highly consistent with the functions of the disordered flora. We focused on an analysis of the relationship between deoxycholic acid, asymmetric dimethylarginine, glucosamine, tauroursodeoxycholic acid, and the disordered flora. This provides a basis for the establishment of the intestine-liver axis in gallstone disease. This research provides a theoretical basis for the research and development of probiotics and prebiotics.

Background: CXCs are important genes that regulate inflammation and tumor metastasis. However, the expression level, prognosis value, and immune infiltration of CXCs in cancers are not clear. Methods: Multiple online datasets were used to analyze the expression, prognosis, and immune regulation of CXCs in this study. Network analysis of the Amadis database and GEO dataset was used to analyze the regulation of intestinal flora on the expression of CXCs. A mouse model was used to verify the fact that intestinal bacterial dysregulation can affect the expression of CXCs. Results: In the three cancers, multiple datasets verified the fact that the mRNA expression of this family was significantly different, the mRNA levels of CXCL3, 8, 9, 10, 14, and 17 were significantly correlated with the prognosis of three cancers. CXCs were correlated with six types of immuno-infiltrating cells in three cancers. Immunohistochemistry of clinical samples confirmed that the expression of CXCL8 and 10 was higher in three cancer tissues. Animal experiments have shown that intestinal flora dysregulation can affect CXCL8 and 10 expressions. Conclusion: Our results further elucidate the function of CXCs in cancers and provide new insights into the prognosis and immune infiltration of breast, colon, and pancreatic cancers, and they suggest that intestinal flora may influence disease progression through CXCs.

TMEM16A, the calcium-activated chloride channel, is broadly expressed and plays pivotal roles in diverse physiological processes. To understand the structural and functional relationships of TMEM16A, it is necessary to fully clarify the structural basis of the gating of the TMEM16A channel. Herein, we performed the protein electrostatic analysis and molecular dynamics simulation on the TMEM16A in the presence and absence of Ca2+. Data showed that the separation of TM4 and TM6 causes pore expansion, and Q646 may be a key residue for the formation of π-helix in the middle segment of TM6. Moreover, E705 was found to form a group of H-bond interactions with D554/K588/K645 below the hydrophobic gate to stabilize the closed conformation of the pore in the Ca2+-free state. Interestingly, in the Ca2+ bound state, the E705 side chain swings 100o to serve as Ca2+-binding coordination and released K645. K645 is closer to the hydrophobic gate in the calcium-bound state, which facilitates the provision of electrostatic forces for chloride ions as the ions pass through the hydrophobic gate. Our findings provide the structural-based insights to understanding the mechanisms of gating of TMEM16A.

Next generation sequencing (NGS)-based tumor profiling identified an overwhelming number of uncharacterized somatic mutations, also known as variants of unknown significance (VUS). The therapeutic significance of EGFR mutations outside mutational hotspots, consisting of >50 types, in nonsmall cell lung carcinoma (NSCLC) is largely unknown. In fact, our pan-nation screening of NSCLC without hotspot EGFR mutations (n = 3, 779) revealed that the majority (>90%) of cases with rare EGFR mutations, accounting for 5.5% of the cohort subjects, did not receive EGFR-tyrosine kinase inhibitors (TKIs) as a first-line treatment. To tackle this problem, we applied a molecular dynamics simulation-based model to predict the sensitivity of rare EGFR mutants to EGFR-TKIs. The model successfully predicted the diverse in vitro and in vivo sensitivities of exon 20 insertion mutants, including a singleton, to osimertinib, a third-generation EGFR-TKI (R2 = 0.72, P = 0.0037). Additionally, our model showed a higher consistency with experimentally obtained sensitivity data than other prediction approaches, indicating its robustness in analyzing complex cancer mutations. Thus, the in silico prediction model will be a powerful tool in precision medicine for NSCLC patients carrying rare EGFR mutations in the clinical setting. Here, we propose an insight to overcome mutation diversity in lung cancer., LC-SCRUM-Japanで構築した日本最大のがん臨床ゲノムデータを活用しスーパーコンピュータで治療薬の効き目を予測 --がんゲノム医療における新たなツールの開発--. 京都大学プレスリリース. 2019-05-13.

Background: Alectinib has shown a greater efficacy to ALK-rearranged NSCLCs in first-line setting; however, most patients relapse due to secondary mutations in ALK such as I1171N and G1202R. Although ceritinib or lorlatinib was shown to be effective to these resistant mutations positive tumor, several cases of ALK-compound mutation-mediated resistance are reported in relapsed patients. However, the overcoming drug has not been clarified yet. Methods: We established lorlatinib-resistant ALK-G1202R-positive tumor in vivo. ENU mutagenesis screening was performed using Ba/F3 cells expressing ALK-I1171N and -G1202R. We performed drug screening to overcome the ALK compound mutations. To evaluate these resistances in silico, we developed a modified computational molecular dynamic simulation (MP-CAFEE). Findings: We identified 14 lorlatinib-resistant ALK-compound mutants, including several mutants recently discovered in lorlatinib-resistant patients. Most of these compound mutants were found to be sensitive to early-generation ALK-TKIs and several BCR-ABL inhibitors. Using our original computational simulation, we succeeded in demonstrating a clear linear correlation between binding free energy and in vitro experimental IC50 value of several ALK-TKIs to single-mutant EML4-ALK expressing Ba/F3 cells and in recapitulating the tendency of binding affinity reduction by the double mutations found in this study. Through the computational simulation, we found that ALK-L1256F single mutant conferred resistance to lorlatinib but increased sensitivity to alectinib. Interpretation: We discovered lorlatinib resistant multiple ALK compound mutations and an L1256F mutation, and found the potential therapeutic strategies to those ALK mutations. Our original computational simulation calculating binding affinity might be applicable for predicting resistance mutations and overcoming drugs in silico. Funding: This study was supported in part by MEXT/JSPS KAKENHI grant number 15H02368 and 17H06327 (to N. Fujita), 16H04715 (to R. Katayama), the grant from the MHLW/AMED grant number 17cm0106203h0002 and 17ck0106231h0002 (to R. Katayama), and the grant from the Vehicle Racing Commemorative Foundation (to R. Katayama). MEXT as “Priority Issue on Post-K computer (Building Innovative Drug Discovery Infrastructure Through Functional Control of Biomolecular Systems)” (to Y. Okuno), and FOCUS Establishing Supercomputing Center of Excellence (to Y. Okuno). This research used the computational resources of the K computer provided by the RIKEN Advanced Institute for Computational Science through the HPCI System Research Project (Project IDs: hp150272, hp160213, hp170275, and ra000018). Declaration of Interest: R Katayama received research grants from Toppan Printing, Taiho Pharmaceutical, Fujifilm, TAKEDA. Ethical Approval: All in vivo studies were conducted through the Institutional Animal Care and Use Committee-approved animal protocols according to the institutional guidelines.

Background Annexin A2 (ANXA2) plays a crucial role in acute pancreatitis (AP). However, its potential mechanism remains unclear. Methods In the present study, we used caerulein-treated AR42J rat pancreatic acinar cells as cell model of AP to investigate the potential functions of ANXA2 and its predicted long noncoding RNA (lncRNA) FOXF1 adjacent noncoding developmental regulatory RNA (lncRNA Fendrr). Cell apoptosis was evaluated by flow cytometry using annexinV-fluorescein isothiocyanate/propidium iodide staining. The expressions of ANAX2 and lncRNA Fendrr were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, Western blot analysis was performed to determine the protein levels of ANXA2, Bcl-2, and Bax. The association between lncRNA Fendrr and ANXA2 was disclosed by RNA pull-down, RNA immunoprecipitation, and electrophoretic mobility shift assays. Results ANXA2 was elevated in caerulein-induced AP model and promoted apoptosis of AR42J cells. LncRNA Fendrr was also upregulated in AP cell model and directly bound ANXA2 protein. Further studies indicated that the interaction between ANXA2 and lncRNA Fendrr contributed to the apoptosis of AR42J cells in AP cell model. Conclusion Our study demonstrated that ANXA2 promoted AP progression via interacting with lncRNA Fendrr in vitro, which will provide a novel insight into the therapeutic target for AP.

Background: Equipoise exists regarding the implementation of evidence-based guidelines for nutritional therapy in critical illness because some previous cluster-randomised controlled trials (cRCTs) demonstrate patient benefits whilst others do not. We aimed to resolve this issue by initiating an appropriately powered cRCT to assess whether active implementation of an evidence-based guideline for nutrition therapy in critical illness could reduce mortality. Methods: We did a multicentre, cluster-randomised, parallel-controlled trial in 97 intensive care units (ICUs) throughout China. We developed an up-to-date, evidence-based nutrition guideline. ICUs randomly allocated to implement the guideline formed a local "intervention team", which actively implemented the guideline using standardized educational materials. ICUs assigned to the control group remained unaware of the guideline. All ICUs enroled critically ill patients who were expected to stay longer than seven days. The primary outcome was all-cause mortality within 28 days of enrolment . Findings Between March, 2018 and July, 2019, we enrolled 1,373 patients at 48 guideline ICUs and 1,399 patients at 49 control ICUs. Implementation of the nutrition guideline resulted in significantly earlier enteral nutrition (EN) initiation (1.20 vs. 1.55 mean days to initiation of EN; difference -0.40 [95% CI, -0.71 to -0.09]; P=0.01) and delayed parenteral nutrition (PN) initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI, 0.44 to 1.67]; P=0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference -1.6% [95% CI -4.3% to 1.2%]; p=0.42) between study groups. Interpretation: Active implementation of an evidence-based guideline can change practice. Our active implementation strategy improved the provision of nutrition therapy to critically ill patients. However, in our cRCT, this improvement in care did not translate to a reduction in mortality. We did not identify any safety concerns associated with the active implementation of our evidence-based guideline for nutrition therapy. Trial Registration: The study was registered in the ISRCTN registry before enrolment commenced (No. ISRCTN12233792). Funding Statement: The study was funded by the Key Research and Development Program Foundation of Jiangsu Province of China (no. BE2015685) and Nutricia, Wuxi, China. Declaration of Interests: Dr. GSD reported receiving academic research grants related to nutrition in critical illness from the Australian National Health and Medical Research Council, Fresenius Kabi Deutschland GmbH and Baxter Healthcare Pty Ltd and speakers honoraria from Fresenius Kabi Deutschland GmbH, Baxter Healthcare Australia, Pty Ltd, Nestle Healthcare, Vevy, Switzerland and Nutricia Pharmaceutical (Wuxi) Co., Ltd. China. Dr. AvZ reports personal fees from Baxter, personal fees from Nestle, personal fees from Fresenius Kabi, grants and personal fees from Nutricia, grants from Cardinal Health grants from Mermaid grants from Lyric, outside the submitted work. Dr. WqL reported receiving speakers honoraria from Nutricia Pharmaceutical (Wuxi) Co., Ltd. China. No other disclosures were reported. Ethics Approval Statement: The study was approved by the local hospital ethics committees of all the participating ICUs. At each site, informed consent was obtained from the patients or their next of kin before enrolment.

Phage display technology in combination with next-generation sequencing (NGS) currently is a state-of-the-art method for the enrichment and isolation of monoclonal antibodies from diverse libraries. However, the current NGS methods employed for sequencing phage display libraries are limited by the short contiguous read lengths associated with second-generation sequencing platforms. Consequently, the identification of antibody sequences has conventionally been restricted to individual antibody domains or to the analysis of single domain binding moieties such as camelid VHH or cartilaginous fish IgNAR antibodies. In this study, we report the application of third-generation sequencing to address this limitation. We used single molecule real time (SMRT) sequencing coupled with hairpin adaptor loop ligation to facilitate the accurate interrogation of full-length single-chain Fv (scFv) libraries. Our method facilitated the rapid isolation and testing of scFv antibodies enriched from phage display libraries within days following panning. Two libraries against CD160 and CD123 were panned and monitored by NGS. Analysis of NGS antibody data sets led to the isolation of several functional scFv antibodies that were not identified by conventional panning and screening strategies. Our approach, which combines phage display selection of immune libraries with the full-length interrogation of scFv fragments, is an easy method to discover functional antibodies, with a range of affinities and biophysical characteristics.

Currently, 28% of all monoclonal antibody (mAb) therapies and 74% of fully human mAb therapies approved by US Food and Drug Administration (FDA) are derived from transgenic animal platforms. In these platforms, the host antibody heavy chain VDJ and light chain VJ repertoire are substituted by their counterparts which are encoded exclusively by human transgenes. These platforms take advantage of the host’s naturally antigen-driven antibody selection and maturation process associated with the primary and secondary immune response. Through immunisations and subsequent antibody discovery using common technologies including hybridoma and single B-cell screening, a large panel of mAbs exhibiting high affinity and specificity against the target antigen along with ideal biophysical characteristics and developability can be obtained. They can be streamlined into clinical development. This chapter gives a comprehensive overview of the transgenic strategies, methods of creating knockout of the endogenous immunoglobulin (Ig) production and generation of transgenic constructs containing human Ig heavy and light chain gene locus. Brief introductions are also given to a list of representative transgenic platforms which have originated in multiple species and can produce human antibodies in various formats. The strategies for antibody discovery in these platforms are also discussed.

Antibody phage display is a powerful platform for discovery of clinically applicable high affinity monoclonal antibodies against a broad range of targets. Libraries generated from immunized animals offer the advantage of in vivo affinity-maturation of V regions prior to library generation. Despite advantages, few studies have described isolation of antibodies from rats using immune phage display. In our study, we describe a novel primer set, covering the full rat heavy chain variable and kappa light chain variable regions repertoire for the generation of an unbiased immune libraries. Since the immune repertoire of rats is poorly understood, we first performed a deep sequencing analysis of the V(D)J regions of VH and VLK genes, demonstrating the high abundance of IGVH2 and IGVH5 families for VH and IGVLK12 and IGVLK22 for VLK. The comparison of gene’s family usage in naïve rats have been used to validate the frequency’s distribution of the primer set, confirming the absence of PCR-based biases. The primers were used to generate and assemble a phage display library from human CD160-vaccinated rats. CD160 represents a valid therapeutic target as it has been shown to be expressed on chronic lymphocytic leukaemia cells and on the surface of newly formed vessels. We utilised a novel phage display panning strategy to isolate a high affinity pool (KD range: 0.399–233 nM) of CD160 targeting monoclonal antibodies. Subsequently, identified binders were tested for function as third generation Chimeric Antigen Receptors (CAR) T cells demonstrating specific cytolytic activity. Our novel primer set coupled with a streamlined strategy for phage display panning enable the rapid isolation and identification of high affinity antibodies from immunised rats. The therapeutic utility of these antibodies was demonstrated in CAR format.

Approximately 15–30% of patients with lung cancer harbor mutations in the EGFR gene. Major EGFR mutations (>90% of EGFR-mutated lung cancer) are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs). Many uncommon EGFR mutations have been identified, but little is known regarding their characteristics, activation, and sensitivity to various EGFR-TKIs, including allosteric inhibitors. We encountered a case harboring an EGFR-L747P mutation, originally misdiagnosed with EGFR-del19 mutation using a routine diagnostic EGFR mutation test, which was resistant to EGFR-TKI gefitinib. Using this minor mutation and common EGFR-activating mutations, we performed the binding free energy calculations and microsecond-timescale molecular dynamic (MD) simulations, revealing that the L747P mutation considerably stabilizes the active conformation through a salt-bridge formation between K745 and E762. We further revealed why several EGFR inhibitors, including the allosteric inhibitor, were ineffective. Our computational structural analysis strategy would be beneficial for future drug development targeting the EGFR minor mutations.

Recently, we and other groups revealed that aberrant expression of Kv10.1 channel, a voltage-gated potassium ion channel, contributes to a variety of tumorigenesis process. Potent and selective inhibitor of Kv10.1 is urgently needed, both as pharmacological tools for studying the physiological functions of this enigmatic channel and as potential leads for development of anti-tumor drugs. In this study, Procyanidin B1, a natural compound extracted from the grape seed, was identified as a potent, specific inhibitor, which can inhibit the Kv10.1 channel in a concentration-dependent manner (IC50 = 10.38 ± 0.87 μM), but has negligible effects on other potassium channels, including Kir2.1, HERG or KCNQ1. It was demonstrated that Procyanidin B1 directly binds to Kv10.1 channel and inhibits its currents, without increasing intracellular Ca2+. Further, three amino acids, I550, T552, and Q557 in the C-linker domain of Kv10.1 were found critical for forming the binding pocket of Procyanidin B1 with Kv10.1 channel. In addition, Procyanidin B1 inhibits migration and proliferation of liver cancer cells (HuH-7 cells, HepG2 cells) through inhibiting Kv10.1, but not in Kv10.1 negatively expressed cell lines. Next, we assayed the tumor suppressing effect of Procyanidin B1 on cell line-derived xenograft mouse model. Our data showed that 15 mg/kg Procyanidin B1 can significantly suppress the growth of the tumor (HepG2) with an inhibition rate of about 60.25%. Compared with cisplatin, Procyanidin B1 has no side effect on the normal metabolism of the mice. The present work indicated that Procyanidin B1 is a proming liver cancer anti-tumor drug, and also confirmed that Kv10.1 can serve as a potential, tumor-specific drug target.

BackgroundThe gut microbiota participates in the metabolism of substances and energy, promotes the development and maturation of the immune system, forms the mucosal barrier, and protects the host from pathogen attacks. Although the pathogenesis of cholesterol gallstones is still not clear, studies have suggested that gut microbiota dysbiosis plays an important role in their formation.MethodsMicrobial DNA from faeces of normal control patients and those of patients with calculi was subjected to 16S rRNA gene sequencing to detect gene expression changes in intestinal microbes. ELISA kits were used to measure free bile acids, secondary bile acids and coprostanol according to the manufacturer’s instructions. The relationship between flora and their metabolites was then analysed.ResultsIn the gallstone group, the diversity of intestinal bacteria and the abundances of certain phylogroups were significantly decreased (p Firmicutes(p p p p p Ruminococcus gnavusgroup could be used as a biomarker to distinguish the gallstone group from the control group.ConclusionWe conclude that intestinal flora imbalance affects bile acid and cholesterol metabolism and is associated with gallstone formation.

Background There is a lack of large-scale epidemiological data on the clinical practice of enteral nutrition (EN) feeding in China. This study aimed to provide such data on Chinese hospitals and to investigate factors associated with EN delivery. Methods This cross-sectional study was launched in 118 intensive care units (ICUs) of 116 mainland hospitals and conducted on April 26, 2017. At 00:00 on April 26, all patients in these ICUs were included. Demographic and clinical variables of patients on April 25 were obtained. The dates of hospitalization, ICU admission and nutrition initiation were reviewed. The outcome status 28 days after the day of investigation was obtained. Results A total of 1953 patients were included for analysis, including 1483 survivors and 312 nonsurvivors. The median study day was day 7 (IQR 2–19 days) after ICU entry. The proportions of subjects starting EN within 24, 48 and 72 h after ICU entry was 24.8% (84/352), 32.7% (150/459) and 40.0% (200/541), respectively. The proportion of subjects receiving > 80% estimated energy target within 24, 48, 72 h and 7 days after ICU entry was 10.5% (37/352), 10.9% (50/459), 11.8% (64/541) and 17.8% (162/910), respectively. Using acute gastrointestinal injury (AGI) 1 as the reference in a Cox model, patients with AGI 2–3 were associated with reduced likelihood of EN initiation (HR 0.46, 95% CI 0.353–0.599; p

Perspiration contains valuable information indicating physiological health. For most wearable perspiration sensors, the sensing element contacts with skin directly. Yet lack of precise fluidic manipulation unit limits accurate and continuous analysis considering perspiration aggregation, evaporation loss and electrolyte reabsorption by sweat glands. The potential skin irritation caused by the chemicals in the sensor is also a safety concern. In this work, we report a wearable microfluidic device with fluidic manipulation unit based on capillary force to address these issues. Inspired by wicking materials for wiping perspiration in our daily life, herein, we use biocompatible threads to collect perspiration by capillary absorption. Then the collected perspiration was spontaneously delivered to a hydrophilic microfluidic channel, forming a continuous flow. Electrodes were embedded in the microfluidic channel for continuous electrochemical analysis and to avoid the direct skin contact. On-body tests demonstrated that continuous perspiration collection, transportation and analysis of Na+ as a proof-of-concept analyte can be achieved using the pump-free epidermal microfluidic device.

Significance Auxin signaling components participate in ethylene-mediated inhibition of root elongation. However, the interplay between TIR1/AFB2-auxin-Aux/indole acetic acid (IAA) signaling and ethylene response remains to be elucidated in detail. In this study, we report an E3 ubiquitin ligase soil-surface rooting 1 (SOR1), which targets a noncanonical Aux/IAA protein OsIAA26 for 26S proteasome-mediated degradation. The E3 ligase activity of SOR1 can be repressed by the canonical Aux/IAA protein OsIAA9, which is the target of OsTIR1/AFB2. Our study identifies a potential regulator that modulates auxin-mediated ethylene response at the auxin signaling level., Plant hormones ethylene and auxin synergistically regulate plant root growth and development. Ubiquitin-mediated proteolysis of Aux/IAA transcriptional repressors by the E3 ubiquitin ligase SCFTIR1/AFB triggers a transcription-based auxin signaling. Here we show that rice (Oryza sativa L.) soil-surface rooting 1 (SOR1), which is a RING finger E3 ubiquitin ligase identified from analysis of a rice ethylene-insensitive mutant mhz2/sor1-2, controls root-specific ethylene responses by modulating Aux/IAA protein stability. SOR1 physically interacts with OsIAA26 and OsIAA9, which are atypical and canonical Aux/IAA proteins, respectively. SOR1 targets OsIAA26 for ubiquitin/26S proteasome-mediated degradation, whereas OsIAA9 protects the OsIAA26 protein from degradation by inhibiting the E3 activity of SOR1. Auxin promotes SOR1-dependent degradation of OsIAA26 by facilitating SCFOsTIR1/AFB2-mediated and SOR1-assisted destabilization of OsIAA9 protein. Our study provides a candidate mechanism by which the SOR1-OsIAA26 module acts downstream of the OsTIR1/AFB2-auxin-OsIAA9 signaling to modulate ethylene inhibition of root growth in rice seedlings.

Here we report an efficient Cu(i)-mediated C–H amination reaction with oximes as amino donors to introduce NH2 groups directly., Here we report an efficient Cu(i)-mediated C–H amination reaction with oximes as amino donors to introduce NH2 groups directly. Various strongly coordinating heterocycles including quinoline, pyrimidine, pyrazine, pyrazole and triazole were tolerated well. The potential utility was further demonstrated in a late-stage modification of telmisartan (an antagonist for the angiotensin II receptor).

Background Epithelial–mesenchymal transition (EMT) and dysregulated microRNAs (miRNAs) have important roles in driving chemoresistance. We previously reported that iASPP is a key EMT inducer and could increase cisplatin resistance in cervical cancer (CC) cells. Herein, we investigate the downstream mechanisms through which iASPP contributes to EMT and cisplatin resistance in CC. Methods By using a lentiviral system, we investigated the effects of iASPP knockdown on CC cell growth and chemosensitivity of CC cells to cisplatin in vivo. We examined if miR-20a, which was up-regulated following iASPP overexpression, would influence metastatic phenotypes and cisplatin resistance in CC cells, and explored the possible molecular mechanisms involved. Results Knockdown of iASPP suppressed CC cell proliferation and sensitized CC cells to cisplatin in vivo. iASPP promotes miR-20a expression in a p53-dependent manner. Upregulation of miR-20a induced EMT and the recovery of CC cell invasion and cisplatin chemoresistance that was repressed by iASPP knockdown. We identified FBXL5 and BTG3 as two direct miR-20a targets. Silencing of FBXL5 and BTG3 restored cell invasion and cisplatin chemoresistance, which was suppressed by iASPP or miR-20a knockdown. Reduced FBXL5 and BTG3 expression was found in CC samples and associated with poor prognosis in CC patients. Conclusions iASPP promotes EMT and confers cisplatin resistance in CC via miR-20a-FBXL5/BTG3 signaling. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0520-6) contains supplementary material, which is available to authorized users.

Identification and isolation of breast cancer stem cells (CSCs) based on CD44/CD24 expression and/or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1). However, the differences among the CD44+/CD24−/low cells, ALDH1+ cells and the overlap between the sub-populations have not been frequently investigated. Thus, it is imperative to improve the understanding of breast CSC with different stem markers. CD44+/CD24−/low, ALDH1+ and ALDH1+CD44+/CD24−/low cell populations were isolated from fresh breast cancer tissues and analyzed by flow cytometry and immunofluorescence. Mammosphere formation, cell proliferation assay and Transwell experiments, were used to analyze self-renewal, proliferation and invasion, respectively, for each sub-population. Finally, in vivo experimentation in mice was performed to evaluate the tumorigenic abilities of the sub-populations. The sub-populations of CD44+/CD24−/low, ALDH1+ and ALDH1+CD44+/CD24−/low in human breast cancer cells, represented the 7.2, 4.6 and 1.5% of the total tumor cell population, respectively. ALDH1+CD44+/CD24−/low cells had the strongest ability of self-renewal, invasion, proliferation and tumorigenicity compared with the other sub-populations (P

The aim of this study was to investigate the role and mechanism of miR-155 in regulating autophagy in a caerulein-induced acute pancreatitis (AP) cellular model. GFP-LC3 immunofluorescence assay was performed to detect autophagy vesicle formation in pancreatic acinar cell line AR42J. AR42J cells were transfected with miR-155 mimic, inhibitor, and corresponding controls to explore the effect of miR-155 on autophagy. The protein levels of LC3-I, LC3-II, Beclin-1, and p62 were analyzed by western blot analysis. Dual-luciferase reporter assay was performed to verify the interaction between miR-155 and Rictor (RPTOR independent companion of MTOR complex 2). The results showed that caerulein treatment induced impaired autophagy as evidenced by an increase in the accumulation of p62 together with LC3-II in AR42J cells, accompanied by miR-155 upregulation. Furthermore, miR-155 overexpression aggravated, whereas miR-155 silencing reduced the caerulein-induced impairment of autophagy. Mechanistically, Rictor was confirmed to be a direct target of miR-155, which could rescue the miR-155 overexpression-mediated aggravation of impaired autophagy. Collectively, these findings indicate that miR-155 aggravates impaired autophagy in caerulein-treated pancreatic acinar cells by targeting Rictor.

As one of the most important crops, maize not only has been a source of the food, feed, and industrial feedstock for biofuel and bioproducts, but also became a model plant system for addressing fundamental questions in genetics. Male sterility is a very useful trait for hybrid vigor utilization and hybrid seed production. The identification and characterization of genic male-sterility (GMS) genes in maize and other plants have deepened our understanding of the molecular mechanisms controlling anther and pollen development, and enabled the development and efficient use of many biotechnology-based male-sterility (BMS) systems for crop hybrid breeding. In this review, we summarize main advances on the identification and characterization of GMS genes in maize, and construct a putative regulatory network controlling maize anther and pollen development by comparative genomic analysis of GMS genes in maize, Arabidopsis, and rice. Furthermore, we discuss and appraise the features of more than a dozen BMS systems for propagating male-sterile lines and producing hybrid seeds in maize and other plants. Finally, we provide our perspectives on the studies of GMS genes and the development of novel BMS systems in maize and other plants. The continuous exploration of GMS genes and BMS systems will enhance our understanding of molecular regulatory networks controlling male fertility and greatly facilitate hybrid vigor utilization in breeding and field production of maize and other crops.

Increasing evidence has demonstrated that dexmedetomidine (DEX) possesses multiple pharmacological actions. Herein, we explored the protective effect and potential molecular mechanism of DEX on lipopolysaccharide (LPS)-induced early acute kidney injury (AKI) from the perspective of antioxidant stress. We found that DEX (30 μg/kg, i.p.) ameliorated the renal dysfunction and histopathological damage (tubular necrosis, vacuolar degeneration, infiltration of inflammatory cells and cast formation) induced by LPS (10 mg/kg). DEX also attenuated renal oxidative stress remarkably in LPS-induced early AKI, as evidenced by reduction in production of reactive nitrogen species, decreasing malondialdehyde levels, as well as increasing superoxide dismutase activity and glutathione content. DEX prevented activator protein-1 translocation, inhibited phosphorylation of I-kappa B (IκB) and activation of nuclear factor kappa B (NF-κB) in LPS-induced early AKI, as assessed by real-time quantitative polymerase chain reaction and protein levels of c-Jun, c-Fos, IκB and NF-κB. Notably, DEX pretreatment had the same effect as intraperitoneal injection of an inhibitor of inducible nitric oxide synthase inhibitor (1400W; 15 mg/kg), and inhibited the activity of renal inducible nitric oxide synthase (iNOS) and decreased the expression of iNOS mRNA and NO production. However, the protective effect of DEX on LPS-induced early AKI was reversed by the alpha 2 adrenal receptor (α2-AR) inhibitor atipamezole, whereas the imidazoline receptor inhibitor idazoxan did not. Taken together, DEX protects against LPS-induced early AKI in rats by inhibiting the iNOS/NO signaling pathway, mainly by acting on α2-ARs instead of IRs.

Accelerated bridge construction (ABC) has been increasingly popular in recent decades, due to various potential advantages compared with traditional cast-in-place (CIP) construction. Grouted splice (GS) sleeve is one of the most widely adopted techniques connecting the pre-fabricated segmental bridge columns and pier footings/caps. Therefore, the behavior of segmental piers with GS should be investigated carefully, especially under earthquake events. This paper investigates the seismic performance of GS piers, considering the influence of columns heights that is scarcely incorporated in previous numerical and experimental studies. The results show that the distribution of plastic regions and hysteretic responses of GS piers are similar to the CIP ones, except for GS regions remaining elastic. The ultimate lateral forces of GS piers are increased by about 10%, since the implementation of GS improves the corresponding section stiffness. While the yield displacement of GS piers accounts over 90% of CIP ones, the displacement capacity and ductility are 40–60% lower, caused by the strain penetration of steel bars and shifting of plastic deformation into grouted beds, as well as shorter plastic regions. Additionally, investigation on coupler rigid length factor ( β ) proposes for the first time that this parameter could be affected by the pier height, H, and might be related to other factors. Suggestions concerning the seismic design of GS piers are finally proposed according to the above results.

Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson’s disease (PD), respectively, which manifested with the selective vulnerability of neuronal cells in substantia nigra (SN) and striatum (STR) regions. However, the underlying molecular mechanism linking parkin with the etiology of PD remains elusive. Here we report that p62, a critical regulator for protein quality control, inclusion body formation, selective autophagy and diverse signaling pathways, is a new substrate of parkin. P62 levels were increased in the SN and STR regions, but not in other brain regions in parkin knockout mice. Parkin directly interacts with and ubiquitinates p62 at the K13 to promote proteasomal degradation of p62 even in the absence of ATG5. Pathogenic mutations, knockdown of parkin or mutation of p62 at K13 prevented the degradation of p62. We further showed that parkin deficiency mice have pronounced loss of tyrosine hydroxylase positive neurons and have worse performance in motor test when treated with 6-hydroxydopamine hydrochloride in aged mice. These results suggest that, in addition to their critical role in regulating autophagy, p62 are subjected to parkin mediated proteasomal degradation and implicate that the dysregulation of parkin/p62 axis may involve in the selective vulnerability of neuronal cells during the onset of PD pathogenesis. Electronic supplementary material The online version of this article (doi:10.1007/s13238-015-0230-9) contains supplementary material, which is available to authorized users.

To overcome the adverse effects of conventional chemotherapy for cancers, various nanoparticles based drug delivery systems have been developed. However, nanoparticles delivering drugs directly to kill tumor cells still faced with challenges, because tumors possessed adopt complex mechanism to resist damages, which compromised the therapeutic efficacy. TMEM16A/CaCCs (Calcium activates chloride channels) has been identified to be overexpressed in lung adenocarcinoma which can serve as a novel tumor specific drug target in our previous work. Here, we developed a novel dual-targeted antitumor strategy via designing a novel nano-assembled, pH-sensitive drug-delivery system loading with specific inhibitors of TMEM16A against lung adenocarcinoma. For validation, we assayed the novel dual-targeting therapy on xenograft mouse model which exhibited significant antitumor activity and not affect mouse body weight. The dual targeting therapy accomplished in this study will shed light on the development of advanced antitumor strategy.

The objective of this study is to optimize the diesel injection parameters, operating parameters and the combustion system of a diesel/natural gas fueled dual fuel engine simultaneously by applying the genetic algorithm. The indicated specific fuel consumption, NOx and CH4 emissions are selected as the optimization objectives. It is shown that almost all the solutions can meet the EURO VI emission limit of the Soot. However, only partial solutions satisfy the EURO V NOx emission limit. More open combustion chambers are chosen than the re-entrant combustion chamber on the Pareto front. A wide range distribution of the combustion bowl radius is found on the Pareto front. However, the diesel fuel spray angle, swirl ratio, EGR (Exhaust Gas Recirculation) rate and compression ratio are gradually concentrated near several optimal points. The response surfaces of ISFC, CH4 and NOx emissions for injection timing vs. EGR rate and spray angle vs. swirl ratio for all the calculated Pareto citizens are achieved.

Autophagy induction in tumors is implicated in tumor malignancy and acquisition of anticancer-drug resistance, and hence, autophagy inhibitors are expected as novel anticancer agents. Atg4B, a cysteine proteinase, is a key enzyme in autophagy process, and considered as one of desirable targets for development of selective autophagy inhibitors. In this study, to search novel inhibitors of Atg4B, we employed the virtual screening approach and differential scanning fluorimetry analysis, and found two compounds 1 (2-methyl-5-oxo-5H-[1,3,4]thiadiazolo-[3,2-a]pyrimidine-6-carboxylic acid) and 17 (methyl 4-({2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]propanoyl} amino)benzoate), showing IC50 values of 10 and 12 µM, respectively, in in vitro LC3 cleavage assay of Atg4B. Molecular docking analysis suggested that 1 and 17 bind to the catalytic domain of Atg4B. The treatments with 1 and 17 significantly suppressed autophagy induction to lung cancer A549 cells by tamoxifen and cisplatin, in which their cotreatments promoted tamoxifen- and cisplatin-induced apoptotic cell death. Moreover, the autophagy suppression by 1 and 17 remarkably restored the sensitivity to cisplatin in cisplatin-resistant A549 cells. Thus, 1 and 17 represent promising leads for future development of potent and selective Atg4B inhibitors that augment existing chemotherapy efficacy.

We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1). This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs) isolated from immunized OmniFlic animals. Using next-generation sequencing antibody repertoire analysis, we measured heavy chain variable gene usage and the diversity of clonotypes present in the lymph node germinal centers of 75 OmniFlic rats immunized with 9 different protein antigens. Furthermore, we expressed 2,560 unique heavy chain sequences sampled from a diverse set of clonotypes as fixed light chain antibody proteins and measured their binding to antigen by ELISA. Finally, we measured patterns and overall levels of somatic hypermutation in the full B-cell repertoire and in the 2,560 mAbs tested for binding. The results demonstrate that OmniFlic animals produce an abundance of antigen-specific antibodies with heavy chain clonotype diversity that is similar to what has been described with unrestricted light chain use in mammals. In addition, we show that sequence-based discovery is a highly effective and efficient way to identify a large number of diverse monoclonal antibodies to a protein target of interest.

The deposition of Amyloid-beta peptides (Aβ) is detected at an earlier stage in Alzheimer’s disease (AD) pathology. Thus, the approach toward Aβ metabolism is considered to play a critical role in the onset and progression of AD. Mounting evidence suggests that lifestyle-related diseases are closely associated with AD, and exercise is especially linked to the prevention and the delayed progression of AD. We previously showed that exercise is more effective than diet control against Aβ pathology and cognitive deficit in AD mice fed a high-fat diet; however, the underlying molecular mechanisms remain poorly understood. On the other hand, a report suggested that exercise induced expression of fibronectin type III domain-containing protein 5 (FNDC5) in the hippocampus of mice through PGC1α pathway. Thus, in the current study, we investigated a possibility that FNDC5 interacts with amyloid precursor protein (APP) and affects Aβ metabolism. As a result, for the first time ever, we found the interaction between FNDC5 and APP, and forced expression of FNDC5 significantly decreased levels of both Aβ40 and Aβ42 secreted in the media. Taken together, our results indicate that FNDC5 significantly affects β-cleavage of APP via the interaction with APP, finally regulating Aβ levels. A deeper understanding of the mechanisms by which the interaction between APP and FNDC5 may affect Aβ production in an exercise-dependent manner would provide new preventive strategies against the development of AD. Electronic supplementary material The online version of this article (10.1186/s13041-018-0401-8) contains supplementary material, which is available to authorized users.

Summary We demonstrate, using the seed-coating method, that melatonin promotes soybean growth, seed production, and stress tolerance by regulating cell division, photosynthesis, carbohydrate metabolism, fatty acid biosynthesis, and ascorbate metabolism., Melatonin is a well-known agent that plays multiple roles in animals. Its possible function in plants is less clear. In the present study, we tested the effect of melatonin (N-acetyl-5-methoxytryptamine) on soybean growth and development. Coating seeds with melatonin significantly promoted soybean growth as judged from leaf size and plant height. This enhancement was also observed in soybean production and their fatty acid content. Melatonin increased pod number and seed number, but not 100-seed weight. Melatonin also improved soybean tolerance to salt and drought stresses. Transcriptome analysis revealed that salt stress inhibited expressions of genes related to binding, oxidoreductase activity/process, and secondary metabolic processes. Melatonin up-regulated expressions of the genes inhibited by salt stress, and hence alleviated the inhibitory effects of salt stress on gene expressions. Further detailed analysis of the affected pathways documents that melatonin probably achieved its promotional roles in soybean through enhancement of genes involved in cell division, photosynthesis, carbohydrate metabolism, fatty acid biosynthesis, and ascorbate metabolism. Our results demonstrate that melatonin has significant potential for improvement of soybean growth and seed production. Further study should uncover more about the molecular mechanisms of melatonin’s function in soybeans and other crops.

In different plant species, aquaporins (AQPs) facilitate water movement by regulating root hydraulic conductivity under diverse stress conditions such as salt and water stresses. To improve survival and yield of crop plants, a detailed understanding of stress responses is imperative and required. We used Glycine soja genome as a tool to study AQPs, considering it shows abundant genetic diversity and higher salt environment tolerance features and identified 62 GsAQP genes. Additionally, this study identifies major aquaporins responsive to salt and drought stresses in soybean and elucidates their mode of action through yeast two-hybrid assay and BiFC. Under stress condition, the expression analysis of AQPs in roots and leaves of two contrasting ecotypes of soybean revealed diverse expression patterns suggesting complex regulation at transcriptional level. Based on expression analysis, we identify GmTIP2;1 as a potential candidate involved in salinity and drought responses. The overexpression of GmTIP2;1 in Saccharomyces cerevisiae as well as in-planta enhanced salt and drought tolerance. We identified that GmTIP2;1 forms homodimers as well as interacts with GmTIP1;7 and GmTIP1;8. This study augments our knowledge of stress responsive pathways and also establishes GmTIP2;1 as a new stress responsive gene in imparting salt stress tolerance in soybean.

Techniques to obtain large quantities of antigen-specific monoclonal antibodies (mAbs) were first established in the 1970s when Georges Kohler and Cesar Milstein immortalized antibody-producing mouse B-lymphocytes by fusion with myeloma cells (http://www.whatisbiotechnology.org/exhibitions/milstein). Combined with the expression of human antibodies in transgenic animals, this technique allowed upon immunization the generation of highly specific fully human mAbs for therapeutic applications. Apart from being extremely beneficial, mAbs are a huge success commercially. However, despite cell fusion generating many useful mAbs questions have been asked about which types of cells are prone to fuse and whether other methods may identify a wider range of binders. The discovery that expression libraries, using Escherichia coli or yeast, produced different specificities was intriguing and more recently Next-Generation Sequencing has identified wide-ranging usage with highly diverse and unique repertoires. Another strategy is the combination of flow cytometry sorting of antigen-binding B lymphocytes and single-cell reverse transcription polymerase chain reaction followed by reexpression, which has identified many high-affinity mAbs.

Epithelial ovarian cancer (EOC) is one of the deadly gynecological malignancies. The function of protein kinase CK2α (CK2α) in EOC is still unknown. Our study aimed to investigate the relationship between the protein expression of CK2α and the tumor progression, the prognosis of human EOC. In this study, we analyzed the expression levels of CK2α through Western blot, using EOC cell lines like A2780, HO8910, COV644, OVCAR3, SKOV3, and the primary normal ovarian surface epithelial (NOSE) cells. Furthermore, OVCAR3 and SKOV3 EOC cells were employed as a cellular model to study the role of CK2α on cell growth, migration, invasion, apoptosis, and cell cycle distribution. In addition, we investigated CK2α protein expression in tumor tissues from patients with EOC by immunohistochemistry and analyzed the association between CK2α expression and clinicopathologic parameters and prognosis of EOC patients. And we found that compared with NOSE cells, CK2α protein expression was increased in A2780, HO8910, OVCAR3, and SKOV3 ovarian cancer cell lines. Decreased CK2α expression suppressed OVCAR3 and SKOV3 cell growth and induced more apoptosis. CK2α knockdown using specific siRNAs inhibited migration and invasion ability of OVCAR3 and SKOV3 cells. In addition, high CK2α protein expression was found in 68.4% (80/117) of EOC patients. Increased CK2α expression of was significantly correlated with FIGO staging and peritoneal cytology. Patients with higher CK2α expression had a significantly poorer overall survival compared with those with lower CK2α expression. Multi-variate Cox regression analysis proved that increased CK2α expression was an independent prognostic marker for EOC. Taken together, our data displayed that CK2α may play a role in tumor aggressive behavior of EOC and could be used as a marker for predicting prognosis of EOC patient. High CK2α expression might predict poor patient survival.