Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

Neurocircuitry of Predatory Hunting / 神经科学通报·英文版

Predatory hunting is an important type of innate behavior evolutionarily conserved across the animal kingdom. It is typically composed of a set of sequential actions, including prey search, pursuit, attack, and consumption. This behavior is subject to control by the nervous system. Early studies used toads as a model to probe the neuroethology of hunting, which led to the proposal of a sensory-triggered release mechanism for hunting actions. More recent studies have used genetically-trackable zebrafish and rodents and have made breakthrough discoveries in the neuroethology and neurocircuits underlying this behavior. Here, we review the sophisticated neurocircuitry involved in hunting and summarize the detailed mechanism for the circuitry to encode various aspects of hunting neuroethology, including sensory processing, sensorimotor transformation, motivation, and sequential encoding of hunting actions. We also discuss the overlapping brain circuits for hunting and feeding and point out the limitations of current studies. We propose that hunting is an ideal behavioral paradigm in which to study the neuroethology of motivated behaviors, which may shed new light on epidemic disorders, including binge-eating, obesity, and obsessive-compulsive disorders.

Neural Circuit Mechanisms Involved in Animals' Detection of and Response to Visual Threats / 神经科学通报·英文版

Evading or escaping from predators is one of the most crucial issues for survival across the animal kingdom. The timely detection of predators and the initiation of appropriate fight-or-flight responses are innate capabilities of the nervous system. Here we review recent progress in our understanding of innate visually-triggered defensive behaviors and the underlying neural circuit mechanisms, and a comparison among vinegar flies, zebrafish, and mice is included. This overview covers the anatomical and functional aspects of the neural circuits involved in this process, including visual threat processing and identification, the selection of appropriate behavioral responses, and the initiation of these innate defensive behaviors. The emphasis of this review is on the early stages of this pathway, namely, threat identification from complex visual inputs and how behavioral choices are influenced by differences in visual threats. We also briefly cover how the innate defensive response is processed centrally. Based on these summaries, we discuss coding strategies for visual threats and propose a common prototypical pathway for rapid innate defensive responses.

Efeitos da atenção dividida no priming de repetição / Effects of divided attention in repetition priming

O presente artigo tem por objetivo investigar possíveis efeitos da atenção dividida no priming de repetição a partir de uma revisão seletiva da literatura. Foram selecionados estudos realizados com testes de priming perceptual e/ou conceitual, nos quais a divisão da atenção foi realizada na fase de codificação ou de recuperação. Em geral, as evidências indicaram que o priming, tanto o perceptual quanto o conceitual, foi afetado pela atenção dividida na codificação quando a tarefa secundária (ou distratora) foi mais demandante de atenção, exigindo resposta frequente e apresentada sincrônica ao estímulo alvo. Poucos estudos foram realizados na recuperação e eles indicaram imunidade do priming perceptual e conceitual à atenção dividida. Conclui-se que os processos de memória implícita podem exigir recursos atencionais na codificação. Implicações teóricas dos resultados são discutidas.

This article aims to investigate possible effects of divided attention on repetition priming from a selective review of the literature. Studies were included if they utilized perceptual and/or conceptual priming tasks, in which the division of attention was performed during encoding or retrieval. In general, the results suggested that perceptual and conceptual priming were affected by divided attention during encoding. This effect occurred when the secondary task (or distractor task) demanded higher levels of attention, requiring frequent task responses and it was presented simultaneously to the memory target stimulus. The few studies investigating retrieval showed that perceptual and conceptual priming are not sensitive to divided attention. Therefore, implicit memory processes may require attentional resources in the encoding. Theoretical implications of the results are discussed.

Prevalence and molecular analysis of multidrug-resistant Acinetobacter baumannii in the extra-hospital environment in Mthatha, South Africa

ABSTRACT Introduction: The presence of Acinetobacter baumannii outside hospitals remains unclear. This study aimed to determine the prevalence of multidrug-resistance (MDR) A. baumannii in the extra-hospital environment in Mthatha, South Africa and to investigate the frequency of carbapenemase-encoding genes. Material and Methods: From August 2016 to July 2017 a total of 598 abattoir samples and 689 aquatic samples were collected and analyzed presumptively by cultural methods for the presence of A. baumannii using CHROMagar™ Acinetobacter medium. Species identification was performed by autoSCAN-4 (Dade Behring Inc., IL) and confirmed by the detection of their intrinsic blaOXA-51 gene. Confirmed MDR A. baumannii isolates were screened for the presence of carbapenemase-encoding genes, ISAba1 insertion sequence and integrase intI1. Results: In total, 248 (19.3%) Acinetobacter species were isolated. Acinetobacter. baumannii was detected in 183 (73.8%) of which 85 (46.4%) and 98 (53.6%) were recovered from abattoir and aquatic respectively. MDR A. baumannii was detected in 56.5% (48/85) abattoir isolates and 53.1% (52/98) aquatic isolates. Isolates showed high resistance to antimicrobials most frequently used to treat Acinetobacter infections such as piperacillin/tazobactam; abattoir (98% of isolates resistant), aquatic (94% of isolates resistant), ceftazidime (84%, 83%), ciprofloxacin (71%, 70%), amikacin (41%, 42%), imipenem (75%, 73%), and meropenem (74%, 71%). All the isolates were susceptible to tigecycline and colistin. All the isolates carried blaOXA-51-like. The blaOXA-23 was detected in 32 (66.7%) abattoir isolates and 11 (21.2%) aquatic isolates. The blaOXA-58-like was positive in 7 (14.6%) and 4 (7.7%) abattoir and aquatic isolates, respectively. Both groups of isolates lacked blaOXA-24-like, blaIMP-type, blaVIM-type, blaNDM-1, blaSIM, blaAmpC, ISAba1 and inI1. Isolates showed high level of Multiple Antibiotic Resistance Index (MARI) ranging from 0.20-0.52. Conclusion: Extra-hospital sources such as abattoir and aquatic environments may be a vehicle of spread of MDR A. baumannii strains in the community and hospital settings.

Enterotoxin-encoding genes in Staphylococcus aureus from buffalo milk / Genes codificadores de enterotoxinas em Staphylococcus aureus no leite de búfalas

This paper investigated the occurrence of Staphylococcus aureus and the detection of enterotoxin-encoding genes of these strains in milk collected from 30 Murrah buffaloes used to produce dairy products in Brazil. A total of 68 strains of Staphylococcus aureus were found as identified by conventional laboratory tests, and thus screened for sea, seb, sec, sed, see, seg, seh and sei enterotoxin-encoding genes by polymerase chain reaction (PCR). Twelve strains containing enterotoxin-amplified genes were found, with higher expression for the sei and seh genes. These results can be attributed to animal health and inadequate cleaning of the equipment, indicating the need for better quality control in animal production and health lines. The results of this study with the presence of pathogens and their enterotoxigenic potential indicate a source of food poisoning, as well as being a pioneering study in the detection of new enterotoxins for buffalo milk.(AU)

Este estudo investigou a ocorrência de isolados de Staphylococcus aureus e a detecção de genes que codificam a enterotoxigenicidade dessas cepas em leite de búfala utilizado na produção de laticínios no Brasil. As amostras foram coletados em 30 búfalos da raça Murrah, identificado por testes laboratoriais convencionais, foram identificados um total de 68 cepas de S. aureus e rastreados para os genes que codificam a enterotoxina sea, seb, sec, sed, see, seg, seh and sei por reação em cadeia da polimerase (PCR). Doze cepas contendo genes da enterotoxina foram amplificadas, com maior expressão para os genes sei e seh. Esses resultados podem ser atribuídos à saúde animal e à higiene inadequada do equipamento, indicando a necessidade de melhor controle de qualidade nas linhas de produção e saúde animal. Os resultados desta pesquisa, com a presença de patógenos e seu potencial enterotoxigênico, indicam uma fonte de intoxicação alimentar, além de ser uma pesquisa pioneira na detecção de novas enterotoxinas para o leite de búfala.(AU)

Mechanism of mesenchymal stem cells-derived extracellular matrix influences on ADSCs: changing microenvironment / 中华整形外科杂志

Objective@#This study aims to explore the potential related gene and mechanism of mesenchymal stem cells (MSCs)-derived extracellular matrix (ECM) promoting the proliferation and differentiation of adipose-derived stem cell (ADSCs), through regulating extracellular microenvironment.@*Methods@#Twelve transcriptomes were analysed using Gene Expression Omnibus (GEO) database, and divided into four groups: (1) ADSCs cultured in Tissue Culture Polystyrene (TCPS) medium with normal human dermal fibroblasts (NHDF)-derived ECM, (2) ADSCs cultured in TCPS medium with bone marrow mesenchymal stem cells (BMSCs)-derived ECM.(3) ADSCs cultured in TCPS medium with ADSCs-derived ECM.(4) ADSCs cultured in TCPS medium as the control group. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA). Software R, Perl and Cytoscape software were used for differential expression analysis and data visualization.@*Results@#Each MSC produced specific extracellular matrix. However, the ADSCs cultured with additive ECM expressed partially different genes and proteins, e. g. The collagen family genes. Furthermore, 3 important molecules: COL4A1, COL11A1, COL15A1 were detected by constructing the interaction relationship between the shared genes and the functional groups. They may affect the proliferation and differentiation of ADSCs by changing microenvironment. The low expression of above molecules, may be related to biological processes and signaling pathways, such as cell repair, nucleotide metabolism, DNA replication, cell cycle, etc.@*Conclusions@#The gene expression of collagen encoding were down-regulated, when ADSCs cultured in the medium with additive ECM derived by MSCs. This may significantly affect the proliferation and differentiation of ADSCs through various pathways.

Expression and clinical significance of melanoma antigen-encoding gene A1 protein in esophageal squamous cell carcinoma / 中国医师进修杂志

Objective To investigate the expression of melanoma antigen- encoding gene (MAGE) A1 protein in esophageal squamous cell carcinoma, and explore its correlation with the clinicopathological factors and prognosis. Methods A retrospective analysis was performed on 197 patients with esophageal squamous cell carcinoma who accepted radical surgical treatment from January 2006 to December 2012. The expressions of MAGEA1 protein in these specimens of cancer tissue and cancer adjacent tissue were detected by immunohistochemistry with tissue microarray technology. Results MAGEA1 protein was expressed in cytoplasm and nucleus of tumor cells. The positive expression rate of MAGEA1 protein in cancer tissue was significantly higher than that in cancer adjacent tissue: 73.6％ (145/197) vs. 5.6％ (11/197), and there was statistical difference (P<0.01). The positive expression of MAGEA1 protein had no correlations with sex, age, history of smoking/drinking, family history of upper gastrointestinal cancer, depth of tumor invasion, lymph node metastasis, tumor differentiation, location and TNM stage (P>0.05). Kaplan-Meier survival analysis result showed that the 5-year survival rate in patients with MAGEA1 protein positive expression was significantly lower than that in patients with MAGEA1 protein negative expression (37.2％ vs. 53.8％), and there was statistical difference (P=0.018). Multivariate analysis result showed that MAGEA1 protein positive expression was an independent predictor of prognosis in esophageal squamous cell carcinoma patients (HR=1.91, 95％CI 1.22 to 2.98, P = 0.004). Conclusions The expression of MAGEA1 protein is abundant in esophageal squamous cell carcinoma, and is related to worse clinical outcome. MAGEA1 protein could be a candidate target for tumor immunotherapy.

Effect of Capsaicin in Inhibiting Migration and Invasion of Breast Cancer MCF-7 Cells by Down-regulating SIRT1 / 中国实验方剂学杂志

Objective: To investigate the effect of capsaicin on the migration and invasion of human breast cancer MCF-7 cells and the underlying molecular mechanism. Method: Three capsaicin intervention groups of different concentrations (25, 50, 75 μmol·L-1) and a blank group were set up. After MCF-7 cells were treated with different concentrations of capsaicin (25, 50, 75 μmol·L-1) for 24 h, the cell migration and invasion abilities were assessed by Transwell migration and invasion assay, respectively. Meanwhile, the mRNA level of silent information regulator 2 homolog 1 (SIRT1) and DNA polymerase δ catalytic subunit p125 encoding gene POLD1 (POLD1) were detected by Real-time polymerase chain reaction (Real-time PCR). The protein levels of SIRT1 and DNA polymerase δ catalytic subunit p125 (p125) were detected by Western blot. Result: Compared with the blank group, the number of transmembrane cells was significantly reduced, and the mobility was significantly decreased (P-1) in MCF-7 cells for 24 h. Capsaicin (25, 50, 75 μmol·L-1) significantly down-regulated the mRNA and protein expressions of SIRT1 (P-1) in MCF-7 cells for 24 h. Furthermore, capsaicin (25, 50, 75 μmol·L-1) also significantly down-regulated the mRNA expression of POLD1 and the protein expression of p125 (P-1) in MCF-7 cells for 24 h. Conclusion: Capsaicin remarkably inhibits the cell migration and invasion of breast cancer MCF-7 cells, and the possible mechanism may be related to the down-regulation of SIRT1 and POLD1 mRNA expression levels and SIRT1 and p125 protein expression levels.

The influence of unitization encoding strategy on directed forgetting effect of associative recognition / 中华行为医学与脑科学杂志

Objective@#To investigate the influence of unitization encoding strategy and the moderating effect of unitization level on directed forgetting effect of associative recognition.@*Methods@#Association recognition paradigm combined with directed forgetting paradigm were employed in this study.The 39 participants acquired by simple random sampling were asked to remember or forget compound words or unrelated word pairs which were randomly presented according to cues.In the retrieval stage, they needed to distinguish " old" or " rearranged" word pairs regardless of the cues.@*Results@#(1) The reversed unitization effect reached significance. The discrimination of compound words (0.43±0.03) was lower than that of unrelated words (0.55±0.03) (F=27.27, P<0.001, ηp2=0.42). For the word pairs (to be remembered, TBR), the discrimination of compound words (0.43±0.03) was lower than that of unrelated words (0.59±0.03) (t=-6.05, P<0.001); for the word pairs (to be forgotten, TBF), the discrimination of compound words (0.43±0.03) was still lower than that of unrelated words (0.50±0.04) (t=-2.30, P=0.025). (2) The directed forgetting effect of associative recognition was significant.However, TBR (0.51±0.03) was more discriminative than TBF (0.46±0.03) (F=4.30, P=0.045, ηp2=0.10). But the difference was mainly reflected in the recognition of unrelated words.TBR (0.59±0.03) was more discriminative than TBF (0.50±0.04) (t=3.19, P=0.003). However, there was no significant difference between TBR (0.43±0.03) and TBF (0.43±0.03) in recognition of compound words.@*Conclusion@#The unitization encoding stratege can simultaneously promote hit rate and false alarm rate.The directed forgetting effect can be eliminated when unitization level is high enough.

Portable Low-Cost MRI System Based on Permanent Magnets/Magnet Arrays

Portable low-cost magnetic resonance imaging (MRI) systems have the potential to enable “point-of-care” and timely MRI diagnosis, and to make this imaging modality available to routine scans and to people in underdeveloped countries and areas. With simplicity, no maintenance, no power consumption, and low cost, permanent magnets/magnet arrays/magnet assemblies are attractive to be used as a source of static magnetic field to realize the portability and to lower the cost for an MRI scanner. However, when taking the canonical Fourier imaging approach and using linear gradient fields, homogeneous fields are required in a scanner, resulting in the facts that either a bulky magnet/magnet array is needed, or the imaging volume is too small to image an organ if the magnet/magnet array is scaled down to a portable size. Recently, with the progress on image reconstruction based on non-linear gradient field, static field patterns without spatial linearity can be used as spatial encoding magnetic fields (SEMs) to encode MRI signals for imaging. As a result, the requirements for the homogeneity of the static field can be relaxed, which allows permanent magnets/magnet arrays with reduced sizes, reduced weight to image a bigger volume covering organs such as a head. It offers opportunities of constructing a truly portable low-cost MRI scanner. For this exciting potential application, permanent magnets/magnet arrays have attracted increased attention recently. A magnet/magnet array is strongly associated with the imaging volume of an MRI scanner, image reconstruction methods, and RF excitation and RF coils, etc. through field patterns and field homogeneity. This paper offers a review of permanent magnets and magnet arrays of different kinds, especially those that can be used for spatial encoding towards the development of a portable and low-cost MRI system. It is aimed to familiarize the readers with relevant knowledge, literature, and the latest updates of the development on permanent magnets and magnet arrays for MRI. Perspectives on and challenges of using a permanent magnet/magnet array to supply a patterned static magnetic field, which does not have spatial linearity nor high field homogeneity, for image reconstruction in a portable setup are discussed.

Protective effect of Yishen Tongluo Recipe against benzo(a)pyrene-induced sperm DNA methylation changes in male rats / 中华男科学杂志

Objective@#To explore the protective effect of Yishen Tongluo Recipe (YTR) against aberrant sperm DNA methylation in male rats exposed to benzo(a)pyrene (BaP).@*METHODS@#Thirty male SD rats of the SPF grade were randomly divided into three groups of equal number: solvent control, BaP exposure and YTR intervention. The animals of the solvent control group were injected intraperitoneally with 0.5% DMSO while those of the other two groups with BaP at 0.1 mg/kg/d, all for 60 days, and at 31 days of BaP exposure, those of the YTR group were treated intragastrically with YTR for 30 days. Then, the left epididymides were harvested from all the rats and sperm suspensions collected and centrifuged for extraction of sperm DNA. The methylated DNA immunoprecipitation sequencing (MeDIP-seq) technique was used to detect the whole-genome DNA methylation in different groups.@*RESULTS@#Exposure to BaP induced the up-regulation of 828 genes encoding mRNA in the sperm DNA, while YTR intervention produced a significant protective effect on the transforming growth factor β3 (TGF-β3), cystic fibrosis transmembrane conductance regulator (CFTR) and recombination activating gene 1 (RAG1), and down-regulated the expressions of 3 227 genes. BaP exposure also caused the up-regulation of 783 genes encoding lncRNA in the sperm DNA, and YTR treatment exhibited an evident protective effect on 62 of the up-regulated genes, induced the down-regulation of 3 378 genes, and showed a protective effect on 56 of the down-regulated genes.@*CONCLUSIONS@#YTR has a protective effect against aberrant sperm DNA methylation in male rats exposed to BaP, which may be associated with lncRNA.

Molecular characteristics and virulence gene profiles of Staphylococcus aureus causing bloodstream infection

ABSTRACT Background: The rate of methicillin-resistant Staphylococcus aureus (MRSA) among the total of S. aureus isolates decreased to 35.3% in 2017 in China. It is unclear whether the molecular characteristics of S. aureus isolates have changed as the rate decreased. Objective: This study aimed to investigate the molecular characteristics and virulence genes profile of S. aureus isolates causing bloodstream infection and analyze the correlation between the prevalence rates of the common sequence types and MRSA. Methods: A total of 112 S. aureus strains from eight hospitals of four cities, including 32 MRSA isolates, were identified and evaluated through multilocus sequence typing, spa typing, and determination of virulence genes. Results: Twenty-five STs were identified, of which ST5 (21.4%) was the most prevalent, whereas the prevalence of ST239 correlated with the rate of MRSA among all S. aureus isolates. Forty-six spa types were identified, of which t2460 (14.3%) was the most common. clfa, hla, seb, fnbA and hlb were the prevailing virulence genes. 81.3% MRSA and 45.0% methicillin-sensitive S. aureus (MSSA) isolates harbored six or more tested virulence genes. ST5-t2460, seldom noted in bloodborne S. aureus isolates in China, was the most common clone. The prevalence of harboring six or more virulence genes in ST5-t2460 and ST188-t189 were 93.8% and 8.3%, respectively. Conclusion: ST5-t2460 was the most common clone in S. aureus causing bloodstream infection followed by ST188-t189, which had never been noted in China before. Moreover, ST5-t2460 harbored more virulence genes than ST188-t189, and the prevalence of ST239 clone decreased with the proportion of MRSA among all S. aureus isolates.

First report of anatoxin-a encoding gene in isolated cyanobacterial strains from Malaysia

@#Aims:This study focus on the presence of cyanobacterial toxin in Malaysia and anatoxin-a-encoding gene was detected in this study and the status of cyanobacterial toxins in Malaysia can now be clarified.Methodology and results:As part of status determination of cyanobacterial toxins in Malaysia, cyanobacterial strains have been isolated from different environments and identified using cyanobacterial16S rRNA gene sequence. PCR assay was carried out to detect the presence of cyanobacterial toxin-encoding genes in these isolated strains by amplifying genes encoded for microcystin, anatoxin-a, cylindrospermopsin and saxitoxin. Using molecular identification of 16S rRNA gene sequences, a total of forty-two cyanobacterial strains were identified, which belongs to eighteen different genera of Synechococcus, Cyanobium, Synechocystis, Chroococcidiopsis, Leptolyngbya, Nodosilinea, Limnothrix, Pseudanabaena, Cephalothrix, Aerosakkonema, Oscillatoria, Alkalinema, Pantanalinema, Planktolyngbya, Scytonema, Nostoc, Hapalosiphonand Symphyonemopsis. The toxicity of these strains was tested using PCR amplification of toxin-encoding genes using specific primers.Conclusion, significance and impact of study:Anatoxin-a (ATX) gene,which involved in the biosynthesis of anatoxin-Awas detected in two isolated strains namelyLimnothrixsp. B15 and Leptolyngbyasp. D1C10.This study focus on the the presence of cyanobacterial toxin in Malaysia can now be determined as potential threat because anatoxin-a-encoding gene was detected in this study and the status of cyanobacterial toxins in Malaysia can now be clarified.

Expression levels of plasma lncRNA MALAT1,LincRNA-p21 and GAS5 in patients with multiple myeloma and chronic lymphocytic leukemia and their diagnostic significances / 吉林大学学报(医学版)

Objective:To explore the differences of the relative expression levels of plasma long chain non encoding RNA(lncRNA)MALAT1,LincRNA-p21 and GAS5 in the patients with multiple myeloma(MM)and chronic lymphocytic leukemia(CLL),and to clarify their significances in the differential diagnosis of MM and CLL. Methods:A total of 60 cases of MM patients(MM group),60 cases of CLL patients(CLL roup)and 60 healthy persons after physical examinations(control group)were selected as the subjects.The plasma levels of lncRNA MALAT,LincRNA-p21 and GAS5 of the subjects in three groups were detected and compared.Results:The relative expression levels of lncRNA MALAT1 and GAS5 in plasma of the patients in MM group were significantly higher than those in the other two groups(P<0.05);the relative expression level of LincRNA-p21 in plasma of the patients in CLL group was significantly lower than those in the other two groups(P<0.05).The area under receiver operating characteristic curve(ROC)(AUC)of plasma LincRNA-p21 in the diagnosis of CLL was 0.850, its 95% confidence interval(CI)was 0.780-0.921. The AUC of plasma lncRNA MALAT1 and GAS5 in the diagnosis of MM were 0.898 and 0.815;their 95% CI were 0.836-0.959 and 0.740-0.890,respectively.The AUC of plasma lncRNA MALAT1,LincRNA-p21 and GAS5 in the differential diagnosis of CLL and MM were 0.878,0.778 and 0.805,and their 95% CI were 0.814 - 0.942,0.691 - 0.865 and 0.727 - 0.882, respectively.Conclusion:The incidence of MM is related with the high expressions of lncRNA MALAT1 and GAS5 in plasma and the incidence of CLL is related with the low expression of LincRNA-p21 in plasma. The relative expression levels of the above lncRNA can be used as the auxiliary indexes in the diagnosis of MM and CLL.

Recognition of fatigue status of pilots based on deep contractive auto-encoding network / 生物医学工程学杂志

We proposed a new deep learning model by analyzing electroencephalogram signals to reduce the complexity of feature extraction and improve the accuracy of recognition of fatigue status of pilots. For one thing, we applied wavelet packet transform to decompose electroencephalogram signals of pilots to extract the δ wave (0.4-3 Hz), θ wave (4-7 Hz), α wave (8-13 Hz) and β wave (14-30 Hz), and the combination of them was used as de-nosing electroencephalogram signals. For another, we proposed a deep contractive auto-encoding network-Softmax model for identifying pilots' fatigue status. Its recognition results were also compared with other models. The experimental results showed that the proposed deep learning model had a nice recognition, and the accuracy of recognition was up to 91.67%. Therefore, recognition of fatigue status of pilots based on deep contractive auto-encoding network is of great significance.

Expression levels of plasma IncRNA MALAT1, LincRNA-p21 and GAS5 in paents with multiple myeloma and chronic lymphocytic leukemia and thir diagnostic significances / 吉林大学学报(医学版)

Objective: To explore the differences of the relative expression levels of plasma long chain non encoding RNA (IncRNA) MALAT1, LincRNA-p21 and GAS5 in the patients with multiple myeloma (MM) and chronic lymphocytic leukemia (CLL), and to clarify their significances in the differential diagnosis of MM and CLL. Methods: A total of 60 cases of MM patients (MM group), 60 cases of CLL patients (CLL roup) and 60 healthy persons after physical examinations (control group) were selected as the subjects. The plasma levels of IncRNA MALAT, LincRNA-p21 and GAS5 of the subjects in three groups were detected and compared. Results: The relative expression levels of IncRNA MALAT1 and GAS5 in plasma of the patients in MM group were significantly higher than those in the other two groups (P<0.05); the relative expression level of LincRNA-p21 in plasma of the patients in CLL group was significantly lower than those in the other two groups (P<0.05). The area under receiver operating characteristic curve (ROC) (AUC) of plasma LincRNA-p21 in the diagnosis of CLL was 0.850, its 95% confidence interval (CI) was 0.780-0.921. The AUC of plasma IncRNA MALAT1 and GAS5 in the diagnosis of MM were 0.898 and 0.815; their 95% CI were 0.836-0.959 and 0.740-0.890, respectively. The AUC of plasma IncRNA MALAT1, LincRNA-p21 and GAS5 in the differential diagnosis of CLL and MM were 0.878, 0.778 and 0.805, and their 95% CI were 0.814 - 0.942, 0.691 - 0.865 and 0.727 - 0.882, respectively. Conclusion: The incidence of MM is related with the high expressions of IncRNA MALAT1 and GAS5 in plasma and the incidence of CLL is related with the low expression of LincRNA-p21 in plasma. The relative expression levels of the above IncRNA can be used as the auxiliary indexes in the diagnosis of MM and CLL.

Effect of adenovirus vector encoding hepatocyte growth factor gene on learning and memory ability and expression of apoptosis protein in hippocampus of rats with hypertension and hyperlipemia / 新乡医学院学报

Objective To investigate the effect of adenovirus vector encoding hepatocyte growth factor gene (Ad-HGF) on learning and memory ability and expression of bcl-2 and bax protein in hippocampal CA1 region of rats with hypertension and hyperlipemia.Methods Thirty male Sprague Dawley rats were randomly divided into control group,model group and Ad-HGF group,with 10 rats in each group.The rats in model group and Ad-HGF group were given bilateral renal artery stenosis operation under aseptic condition to establish experimental renal hypertension;one week after operation,the rats were fed with high fat diet for 16 weeks.The rats in control group were only separated the bilateral renal arteries,and then were given normal diet for 16 weeks after the operation.After modeling,the rats in Ad-HGF group were injected with Ad-HGF (10 μL) throuth cisterna magna;the rats in control group and model group were injected with the same volume of saline through cisterna magna.The learning and memory ability of rats were evaluated by Morris water maze test at 10 d after administration;the expression of bcl-2 and bax protein in hippocampus CA1 region were detected by immunohistochemistry.Results The escape latency of rats in model group was significantly longer than that in the control group,the number of cross platform and target quadrant time were significantly less than those in the control group (P ＜ 0.05);the escape latency of rats in Ad-HGF group was significantly shorter than that in the model group,the number of cross platform and target quadrant time were significantly more than those in the model group (P ＜ 0.05).Compared with the control group,the number of the bcl-2 and bax protein positive cells in hippocampal CA1 region of rats in the model group was increased,and the ratio of bcl-2/bax was decreased(P ＜0.05);compared with the model group,the number of the bcl-2 protein positive cells in hippocampal CA1 region of rats in AdHGF group was increased,but the number of bax protein positive cells was decreased,and the ratio of bcl-2/bax was increased (P ＜ 0.05).Conclusion Exogenous Ad-HGF can significantly improve the learning and memory ability of rats with hypertensive and hyperlipidemia,and it play a neuroprotective role in the brain,which may be related to the inhibition of apoptosis of hippocampal neurons.

Research advances in picornavirus 2C gene and its encoding protein / 中国人兽共患病学报

Picornaviridae 2C gene is relatively conservative,whose encoded protein is a non-structural protein.The 2C protein is in an earlier detection and only can be detected during virus replicatin.The 2C protein has multiple fuctions:the role of AAA+ helicase activity,invasion cells by autophagy pathway,abduction cells on inflammation and apoptosis;the interaction with other proteins such as 2B and 3C that might be induced by 2C protein,which can participate in the pathogenic process in a way.Above all,we mainly outline the reseach advances on Picornaviridae 2C gene and its encoded protein,in order to provide some superficial reference for its further study.

Effects of IGF-1 on PRNP expression and APP metabolism of PC12 cells / 上海交通大学学报（医学版）

Objective·To investigate the effects of insulin-like growth factor 1 on prion encoding gene (PRNP) expression and amyloid precursor protein (APP) metabolism of PC12 cells. Methods·After PC12 cells were treated with 20, 40, 80 ng/mL IGF-1 for 24 h, real-time PCR was used to detect the mRNA expression levels of PRNP, and Western blotting was used to detect the protein levels of AKT, phosphorylation of AKT (pAKT), ERK and phosphorylation of AKT (pERK). The level of β-amyloid 42 (Aβ42) in supernatant fluid was detected by ELISA. Results·Compared with the blank control group, the expression of PRNP mRNA in Alzheimer's disease (AD) model group was increased significantly (P0.05). Compared with the blank control group, the level of Aβ42 in supernatant fluid of model group was decreased significantly with the increasing of IGF-1 concentration. The expression level of Aβ42 was decreased significantly in 40 and 80 ng/ml IGF-1 treatment group (P<0.05). The expression of AKT/pAKT, ERK/pERK in AD model group was significantly increased along with the increasing of IGF-1 concentration (P<0.05). Conclusion·IGF-1 could regulate the expression of PRNP gene and effect the metabolism of APP, which may be associated with PI3K/AKT, MAPK/ERK1/2 signaling pathway.