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Glioblastoma (GBM) is the most frequently observed and aggressive type of high-grade malignant glioma. Temozolomide (TMZ) is the primary agent for GBM treatment. However, TMZ resistance remains a major challenge. In this study, we report that MDK is overexpressed in GBM, which leads to enhanced proliferation, apoptosis inhibition, increased invasion and TMZ resistance in GBM cells. It was also determined that MDK could significantly improve the stem-like properties of GBM cells. Mechanistically, MDK enhanced p-JNK through Notch1 and subsequently increased the expression of stemness markers, such as CD133 and Nanog, thereby promoting TMZ resistance. Finally, xenograft experiments and clinical sample analysis also demonstrated that MDK knockdown could significantly inhibit tumor growth in vivo, and the expression of MDK was positively correlated with Notch1, p-JNK and CD133. This study revealed that MDK induces TMZ resistance by improving the stem-like properties of GBM by upregulating the Notch1/p-JNK signaling pathway, which provides a possible target for therapeutic intervention of GBM, especially in TMZ-resistant GBM with high MDK expression.

Additional file 2: Supplementary Table 1. The specific primers of the three target genes and internal reference gene (actin).

Additional file 4: Supplementary Table 3. Basic information of 27 DEGs mapped to specific metabolic pathways with corresponding KO numbers.

Additional file 4: Supplementary Table 3. Basic information of 27 DEGs mapped to specific metabolic pathways with corresponding KO numbers.

Additional file 3: Supplementary Table 2. BUSCO assessment the assembly results of test sample dataset (LPN1) based on three assemblers.

At present, attention mechanism has been widely applied to the fields of deep learning models. Structural models that based on attention mechanism can not only record the relationships between features position, but also can measure the importance of different features based on their weights. By establishing dynamically weighted parameters for choosing relevant and irrelevant features, the key information can be strengthened, and the irrelevant information can be weakened. Therefore, the efficiency of deep learning algorithms can be significantly elevated and improved. Although transformers have been performed very well in many fields including reinforcement learning, there are still many problems and applications can be solved and made with transformers within this area. MARL (known as Multi-Agent Reinforcement Learning) can be recognized as a set of independent agents trying to adapt and learn through their way to reach the goal. In order to emphasize the relationship between each MDP decision in a certain time period, we applied the hierarchical coding method and validated the effectiveness of this method. This paper proposed a hierarchical transformers MADDPG based on RNN which we call it Hierarchical RNNs-Based Transformers MADDPG(HRTMADDPG). It consists of a lower level encoder based on RNNs that encodes multiple step sizes in each time sequence, and it also consists of an upper sequence level encoder based on transformer for learning the correlations between multiple sequences so that we can capture the causal relationship between sub-time sequences and make HRTMADDPG more efficient., 10 pages

A novel Gram-stain-positive, catalase- and oxidase-positive, endospore-forming bacterium, designated GY 10110T, was isolated from mangrove soil collected from Qinzhou, Guangxi province, China. Cells were aerobic, motile with peritrichous flagella and rod-shaped. The strain grew at 15–37 °C (optimum, 28 °C), at 0–3 %(w/v) NaCl (1 %) and at pH 6.0–9.0 (pH 7.0). The major fatty acids of strain GY 10110T were anteiso-C15 : 0, iso-C15 : 0 and iso-C16 : 0. The predominant menaquinone was MK-7. The cell-wall peptidoglycan contained meso-diaminopimelic acid. The polar lipid profile comprised diphosphatidylglycerol, phosphatidylethanolamine, phosphoglycolipid, glycolipid, two unidentified aminophospholipids and three unidentified phospholipids. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain GY 10110T was closely related to Falsibacillus pallidus CCTCC AB 207188T (98.0 % sequence similarity) and Bacillus oceanisediminis CGMCC 1.10115T (96.9 %), respectively. The G+C content of strain GY 10110T based on the whole genome sequence was 42.3 mol%. The novel strain showed an average nucleotide identity (ANI) value of 77.8 % and a digital DNA–DNA hybridization (dDDH) value of 15.6 % with Falsibacillus pallidus CCTCC AB 207188T based on draft genome sequences, followed by Bacillus oceanisediminis CGMCC 1.10115T with ANI and dDDH values of 75.2 and 12.8 %, respectively. The results of the polyphasic taxonomic study, including phenotypic, chemotaxonomic and phylogenetic analysis, showed that strain GY 10110T represents a novel species of the genus Falsibacillus , for which the name Falsibacillus albus sp. nov. is proposed. The type strain is GY 10110T (=CGMCC 1.13648T=NBRC 113502T).

A novel Gram-negative bacterium, non-motile and short rod-shaped, designated strain GY511T, was isolated from the intestines of fish collected from Maowei Sea, China. Growth occurred at pH 6.0–9.0 (optimum 7.0), 4–37 °C (optimum 28 °C) and at 0–2.5% (w/v) NaCl (optimum 1.0%). The result of 16S rRNA gene sequence analysis showed that strain GY511T is closely related to O. oryzae NBRC 113109T (97.6%), O. konkukae DSM 105395T (97.4%), Ottowia beijingensis CGMCC 1.12324T (95.9%), Ottowia pentelensis DSM 21699T (95.2%) and Ottowia thiooxydans DSM 14619T (95.0%). The DNA–DNA hybridization values of strain GY511T with O. oryzae NBRC 113109T and O. konkukae DSM 105395T were 35.4 ± 3.1% and 26.3 ± 1.8%, respectively. The major fatty acids (> 10%) were identified as summed feature 3 (C16:1ω7c and/or C16:1ω6c), C16:0 and summed feature 8 (C18:1ω7c and/or C18:1ω6c) and the major respiratory quinone was ubiquinone-8 (Q-8). The polar lipids comprised diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylmethylethanolamine, two unidentified aminolipids and an unidentified phospholipid. The G+C content of the genomic DNA was 62.9 mol%. Thiosulfate could be utilized as co-substrate for aerobic growth and was oxidised to sulfate. On the basis of phenotypic, chemotaxonomic and molecular data, strain GY511T is considered to represent a novel species of the genus Ottowia, for which the name Ottowia flava sp. nov. is proposed. The type strain is GY511T (= NBRC 113500T = DSM 107425T = CGMCC 1.13650T).

Resampling detection plays an important role in identifying image tampering, such as image splicing. Currently, the resampling detection is still difficult in recompressed images, which are yielded by applying resampling followed by post-JPEG compression to primary JPEG images. Except for the scenario of low quality primary compression, it remains rather challenging due to the widespread use of middle/high quality compression in imaging devices. In this paper, we propose a new convolution neural network (CNN) method to learn the resampling trace features directly from the recompressed images. To this end, a noise extraction layer based on low-order high pass filters is deployed to yield the image residual domain, which is more beneficial to extract manipulation trace features. A dual-stream CNN is presented to capture the resampling trails along different directions, where the horizontal and vertical streams are interleaved and concatenated. Lastly, the learned features are fed into Sigmoid/Softmax layer, which acts as a binary/multiple classifier for achieving the blind detection and parameter estimation of resampling, respectively. Extensive experimental results demonstrate that our proposed method could detect resampling effectively in recompressed images and outperform the state-of-the-art detectors.

Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress. mTOR signaling presents both cardioprotective and cardiotoxic effects on the diabetic heart, which interplays with oxidative stress directly or indirectly. Antihyperglycemic agent metformin and newly found free radicals scavengers, Sirt1 and CTRP9, may serve as promising pharmacological therapeutic targets. In this review, we will focus on the role of oxidative stress and mTOR signaling in the pathophysiology of MI/R injury in diabetes and discuss potential mechanisms and their interactions in an effort to provide some evidence for cardiometabolic targeted therapies for ischemic heart disease (IHD).

As the world developing rapidly, worldwide educational system needs an urgent breakthrough on establishing a rational and feasible innovative talents training system. The paper takes as the case study training path within Student Science and Technology Association of Shijiazhuang University of Economics, elaborating the six features of innovative talents in their growing up. They are, but not limited to, “difference”, “sustainability”, “publicity”, “perseverance”, “exploring” and “inclusiveness”. It describes the association's constructing a scientific and comprehensive training system based on its exploration. Besides, the paper discusses the way to reform teaching and learning system as well as the training talents, referring to the experience of students' self-managing. In the end, the paper tries to offer meaningful approaches to building an effective innovative education.

In our previous study, a novel human testis-specific gene, SPATA12, was identified using the digital differential display program. In the current study, both SPATA12 mRNA and protein levels in the developmental stage of the testis were detected by SYBR real-time reverse transcriptase polymerase chain reaction and Western blot. A high level of SPATA12 gene expression was observed in normal adult testis but was completely absent in fetal testis. Both in situ hybridization and immunohistochemical analysis showed that SPATA12 was expressed in seminiferous tubules of adult testis—more precisely in spermatocytes, spermatids, and spermatozoa—but there was no expression in Sertoli and Leydig cells. These results showed that SPATA12 is a stage-specific and germ cell—specific gene, which suggests that it must be involved in the development of testicular maturation. It was also found that the expression level of SPATA12 mRNA in the testes of infertile men was associated with the amount and density of germ cells. With a decrease in the number of germ cells, the expression of SPATA12 mRNA was lower. In addition, the signal in the testes of patients with cryptorchidism or Sertoli cell only syndrome was not detected. Flow cytometry analysis of SPATA12 in human HeLa cells and mouse GC-1 spg germ cells indicated that the expression of the SPATA12 gene may delay the progression of G1 to S in the cell cycle. SPATA12 was also shown to be lost in testicular germ cell tumors both at the level of transcription and translation. We hypothesized that the putative function of SPATA12 is to maintain the cell in a differentiated state and/or to suppress cell proliferation.

Derris eriocarpa How is an important medicinal plant, which is used as Zhuang ethnomedicine and Dai ethnomedicine to treat various diseases. One new compound, 3',4'-di-O-methylene-5-hydroxy-7-methoxy-6-isopentenyl isoflavone (1) and a known synthetic but new naturally occurring compound trans-3,4,5-trimethoxy-4'-isopentenyloxyl-stilbene (2), together with five known compounds, 5,7-dimethoxy-6-(3-methyl-2-butenyl)-4'-hydroxyl isoflavones (3), robustone (4), trans-3,4,5,4'-tetramethoxy-stilbene (5), robustic acid (6), and robustin (7) were isolated from the stem of D. eriocarpa. Spectroscopic analysis revealed the chemical structures of compounds 1-7.. Compounds 1 and 3 exhibited significant scavenging activities against 1,1-diphenyl-2-picrylhydrazyl radical and superoxide anions. Compounds 1-3 exhibited potent antiproliferative activity on Hela cells.

Relevance feedback has been developed to improve retrieval performance effectively in Content Based Image Retrieval (CBIR). This paper introduces a relevance feedback system for CBIR with both short-term relevance feedback and long-term learning. In short-term relevance feedback, query reweighting algorithm, support vector machines (SVM), and genetic algorithm are adopted. In long-term learning, the expanded-judging model with index table is used for analyzing the historical log data. Experimental results show that among short-term feedback algorithms, the SVM gets the best feedback results, and for the use of our proposed expanded-judging model in long-term learning, the recall of the retrieval system is improved more than 30% in average.

Prostate cancer (PCa) is a major health problem in males in the United States. Its lethality is mostly attributed to the primary tumor metastasizing to distant sites that are highly resistant to conventional therapies. Serum Prostate Specific Antigen (PSA) is the only protein biomarker used in clinic for prediction of prostate cancer recurrence following local therapies. Nonetheless, PSA lacks the ability to predict the behavior of an individual tumor in an individual patient. Therefore, development of reliable biomarkers for detection of metastatic potential in primary tumors, as well as discovery of new therapeutic targets, is in a great need for improved disease survival and management. Tumor metastasis is a multistep process involving extravasation of a cancer cell subsequent invasion and expression at a site distal to the primary tumors. Cell surface glycoproteins play pivotal roles as recognition molecules in a range of cell communication and adhesion events. Aberrant cell surface glycosylation has been reported in various cancers including PCa, and strongly correlated with prognosis and metastasis. However, the staggering complexity of glycans renders their analysis extraordinarily difficult. This research project aims to develop a mass spectrometry-based glycoproteomic approach for the selective isolation and identification of cell surface glycoproteins from cellular samples, and apply this technology to the discovery of new glycoprotein biomarkers which are indicative of prostate cancer progression and metastasis. To this end, cell surface glycosylation patterns were characterized by lectin flow cytometry and lectin cytochemistry on a human syngeneic PCa cell metastatic model, PC3 and its two variants with different metastatic potentials. It was found that metastatic potentials of PC3 variants were inversely correlated with cell surface α2-6 sialic acid levels. Targeted to cell surface sialoglycoproteins, a new glycoproteomic approach was successfully developed, which combined selective metabolic labeling of cell surface sialyl glycans, chemically probing the labeled sugar with a biotin tag, affinity purification of sialylated proteins, SDS-PAGE separation, and subsequent LC-MS/MS for protein identification. Application of this methodology in our prostate cancer model system resulted in unique identification of a total of 80 putative cell surface sialoglycoproteins differentially expressed between PC3 variants. After prioritization of the candidate biomarkers, one cell-based prioritized biomarker CUB-domain-containing protein 1 (CDCP1) was verified in prostate cancer cell lines and clinical samples, including tissues and body fluids, by immunoassays. Results indicated that expression of CDCP1 protein is dysregulated in prostate cancer and it has potential utility as a therapeutic target and a diagnostic marker for PCa progression. Overall, the data from this research project provided the proof-of-principle evidence for our targeted glycoproteomic approach, which we believe will help expedite the discovery of new cancer biomarkers and therapeutic targets in diseases and delineation of signal transduction pathways on a global scale.

The ability of hand operation is an important part of ergonomics. The evaluation of hand works is theoretically and practically important to both the evaluation of human hands potential and ergonomically design of tools. The research is based on the theory of anthropometry and ergonomics, a set of device of hand operating capacity is designed through research of basic method and step of hand operating capacity. The method and discipline of hand function measurement are explored through the device of hand capacity evaluation.

Background To investigate the feasibility of gene therapy in treating Epstein-Barr virus (EBV)-associated cancer by employing the suicide gene, herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV), which uses the signaling pathway through the HIV-long terminal repeat (LTR) gene which is expressed from a nuclear factor-κB (NF-κB)-binding motif-containing promoter that is regulated by EBV-latent membrane protein 1 (LMP1) via NF-κB. Methods First, we constructed the plasmid pVLTR-tk, which was regulated by EBV-LMP1 via NF-κB, and then investigated the cytotoxic effect of the pVLTR-tk/GCV on cancer cells, using MTT assays, clonogenic assays, flow cytometry, and animal experiments. Results The activation of TK was increased after transfection of the pVLTR-tk into the EBV-LMP1 positive cells. After GCV treatment, the clonogenicity and survival of the cells substantially declined, and a bystander effect was also observed. The LMP1 positive cells exhibited remarkable apoptosis following pVLTR-tk/GCV treatment, and the pVLTR-tk/GCV restrained tumor growth in vivo for EBV-LMP1 positive cancers. Conclusion The pVLTR-tk/GCV suicide gene system may be used as a new gene targeting strategy for EBV-associated cancer.

A-weighted level is the main method to evaluate the noise. The method of noise evaluation has some drawbacks because it can not include all kinds of sound and all factors which affects the work efficiency of operators. The sound includes music and song, language, the nature sound and noise, which have different effect on the work efficiency of operators. The factors effecting human annoyance include the kind of sound, special sound, A-weighted level, the different operating environment, the sound relationship with operators and so on. In the paper, the sound factors effecting human annoyance would be found and analyzed and their validity would be analyzed through some examples. Through these factors and their weights, the value of annoyance on some noise can be got which can be used to control the sound of operating environment and improve the work efficiency of operators

As important foundation for product design, ergonomics studying has been necessary for most engineering students. Ergonomics experiments can help students obtain perceptual knowledge of human factors. Through research of integrating multimedia technology into ergonomics experiments teaching, the author hopes to improve the teaching effect of ergonomics experiment. By introducing some film shooting technology, the multimedia courseware can clearly present the process of ergonomics experiment and by means of adding more ergonomics related background knowledge, the multimedia courseware can provide students rich useful information for ergonomics study. The development of ergonomics multimedia courseware gives a novel idea is to improve teaching effect.

ObjectivesThe objective of this study was to evaluate the safety and efficacy of the surgical versus transcatheter approach to correct perimembranous ventricular septal defects (pmVSDs) in a prospective, randomized, controlled clinical trial.BackgroundpmVSD is a common congenital heart disease in children. Surgical closure of pmVSD is a well-established therapy but requires open-heart surgery with cardiopulmonary bypass. Although the transcatheter approach is associated with significant incidence of complete atrioventricular block, it may provide a less invasive alternative. Critical comparison of the safety and efficacy of the 2 interventions necessitates a prospective, randomized, controlled trial.MethodsBetween January 2009 and July 2010, 229 children with pmVSD were randomly assigned to surgical or transcatheter intervention. Clinical, laboratory, procedural, and follow-up data over a 2-year period were compared.ResultsNeither group had mortality or major complications. However, statistical analysis of the 2 groups demonstrated significant differences (p < 0.001) in minor adverse events (32 vs. 7), quantity of blood transfused, duration of the procedure, median hospital stay, median intensive care unit stay, median hospitalization cost, and median blood loss. During a median follow-up of 2 years, the left ventricular end-diastolic dimension of both groups returned to normal and there was no difference in closure rate, adverse events, and complications between groups.ConclusionsTranscatheter device closure and surgical repair are effective interventions with excellent midterm results for treating pmVSD in children. Transcatheter device closure has a lower incidence of myocardial injury, less blood transfused, faster recovery, shorter hospital stay, and lower medical expenses. (Transcatheter Closure Versus Surgery of Perimembranous Ventricular Septal Defects; NCT00890799)