Semisupervised Multiple Choice Learning for Ensemble Classification.

Ensemble learning has many successful applications because of its effectiveness in boosting the predictive performance of classification models. In this article, we propose a semisupervised multiple choice learning (SemiMCL) approach to jointly train a network ensemble on partially labeled data. Our model mainly focuses on improving a labeled data assignment among the constituent networks and exploiting unlabeled data to capture domain-specific information, such that semisupervised classification can be effectively facilitated. Different from conventional multiple choice learning models, the constituent networks learn multiple tasks in the training process. Specifically, an auxiliary reconstruction task is included to learn domain-specific representation. For the purpose of performing implicit labeling on reliable unlabeled samples, we adopt a negative l1 -norm regularization when minimizing the conditional entropy with respect to the posterior probability distribution. Extensive experiments on multiple real-world datasets are conducted to verify the effectiveness and superiority of the proposed SemiMCL model.

Fosthiazate inhibits root-knot disease and alters rhizosphere microbiome of Cucumis melo var. saccharinus.

Root-knot nematodes especially Meloidogyne spp. are considered as most destructive obligate parasites that substantially reduce crop yield and quality. Fosthiazate is an efficient organothiophosphate chemical with nematicidal activity against Meloidogyne spp. The present study aimed to analyze the efficacy of fosthiazate against root-knot disease in Cucumis melo var. saccharinus and its potential effects on rhizosphere microbiome and metabolites. The fosthiazate (40%) was applied two times by spraying on the day of transplanting and during the pollination period (after 31 days). Samples from treatment (fosthiazate 40%: MF) and control groups (untreated plants; MCK) were analysed through metagenomic and metabolomic profiling of rhizospheres. Results revealed that root-knot index of the MF group (9.26 ± 1.28) was significantly (p < 0.05) lower than the MCK group (22.06 ± 0.71) with a control effect of 57.85% after 31 days of the first spray, whereas fosthiazate efficacy reduced to 31.87% after 38 days of second application with significantly (p < 0.05) different root-knot index values (MF: 56 ± 1.43 and; MCK: 82.26 ± 3.87). However, Cucumis melo var. saccharinus fruit yield in both groups (MCK: 21.1 ± 0.9 and MF: 21.53 ± 0.85) showed no differences (p > 0.05). Metagenomic profiling revealed Proteobacteria, Acidobacteriota, and Firmicutes as predominant phyla and Bacillus, Sphingomonas, and Acidibacter as predominant genera in rhizosphere soil samples of both MF and MCK groups. Further, a t-test revealed higher differential enrichment of Firmicutes at phylum level and Bacillus at genus level in MF than MCK. Metabolomic profiling of rhizospheric soil revealed a total of six differential metabolites (p < 0.05), four of them (Sucrose, Hexaonic acid 1, (Z)-9-Octadecenamide 1, and Hexadecanamide) were up-regulated in MF group, whereas two of them (2,3,4-Trihydroxy-3-(Hydroxymethyl) Butanol and Sulfurous acid, 2, ethylhexylundecyl ester) were down-regulated in CK group. Our study concluded that fosthiazate exhibits a better control over the rook-knot disease in the short term and resulted in trackable changes in rhizosphere microbiome and metabolome.

Zinc finger E-box-binding homeobox 2 (ZEB2) regulated by miR-200b contributes to multi-drug resistance of small cell lung cancer.

Zinc finger E-box-binding homeobox 2 (ZEB2) was closely related to the oncogenesis, development and response to chemotherapy of cancer. However, its biological functions in small cell lung cancer (SCLC) remain unknown. The aim of this study is to investigate the roles of ZEB2 in chemoresistance of SCLC and its possible molecular mechanism. Expression of ZEB2 was examined in sixty-eight cases of SCLC tissues by immunohistochemistry. Knockdown of ZEB2 was carried out in SCLC multidrug resistant cells (H69AR) to assess its influence on chemoresistance. The results showed that ZEB2 was expressed in 23.5% (16/68) of SCLC. Overexpression of ZEB2 was associated with the poor pathologic stage of SCLC (P < 0.001 by the Fisher's Exact Test) and the shorter survival time (by the Kaplan-Meier method). Inhibition of ZEB2 expression using small interfering RNA in H69AR cells sensitized cancer cells to chemotherapeutic drugs through increasing drug-induced cell apoptosis accompanied with S phase arrest. In silico analysis demonstrated that there are complementary binding sites between miR-200b and ZEB2 3'-UTR, and identified miR-200b as a potential regulator of ZEB2. We found that miR-200b was down-regulated in the resistant cells and enforced expression of miR-200b by miRNA mimics increased cell sensitivity. Overexpression of miR-200b led to the downregulation of ZEB2 at protein level. Luciferase reporter gene assay showed that 3'UTR ZEB2 activity was regulated by miR-200b. Our results suggest that ZEB2 modulates drug resistance and is regulated by miR-200b. All findings provide insight into the ZEB2 signaling mechanism and ZEB2 may be a potentially novel target for multi-drug resistance in SCLC.

[Role of homeobox gene A5 in multidrug resistance of human small cell lung cancer cells].

OBJECTIVE: To investigate the role of homeobox gene A5 (HOXA5) in multidrug resistance of human small cell lung cancer (SCLC) cells and the possibility of using HOXA5 as the therapeutic targets for SCLC treatment. METHODS: We examined HOXA5 mRNA and protein expressions in chemosensitive human SCLC cells (H69) and the multidrug-resistant SCLC cells (H69AR) using quantitative real-time PCR and immunoblotting. HOXA5 expression was then enhanced or suppressed by transfection of the cells with HOXA5 expression plasmids or small interference RNA (siRNA), and the chemosensitivity of transfected cells to cisplatin (DDP) and etoposide (VP-16) was evaluated using cell counting kit-8 (CCK8) assay. RESULTS: H69 cells showed a 8.99-fold higher expression of HOXA5 than H69AR cells. HOXA5 knockdown caused obvious reductions in the chemosensitivity of H69 cells to DDP and VP-16 with increased cells in G0/G1 phase; conversely, HOXA5 enhancement resulted in an increased sensitivity of H69AR cells to DDP and VP-16. CONCLUSION: HOXA5 may play an important role in multidrug resistance of SCLC and can be a potential therapeutic target in clinical treatment of SCLC.

MiR-296-3p regulates cell growth and multi-drug resistance of human glioblastoma by targeting ether-à-go-go (EAG1).

MicroRNAs (miRNAs) - short non-coding RNA molecules - post-transcriptionally regulate gene expressions and play crucial roles in diverse biological processes such as development, differentiation, apoptosis and proliferation. In order to investigate the possible role of miRNAs in the development of multi-drug resistance (MDR) in human glioblastoma, we first detected (by Western blotting, real-time polymerase chain reaction [RT-PCR] and immunohistochemistry) the expression of miR-296-3p and ether-à-go-go (EAG1 or KCNH1) in U251 cells, U251/imatinib mesylate (U251AR cells) and clinical specimens. The results showed that miR-296-3p was down-regulated in U251AR cells, concurrent with the up-regulation of EAG1 protein, compared with the parental U251 cell line. In vitro drug sensitivity assay demonstrated that over-expression of miR-296-3p sensitised glioblastoma (GBM) cells to anticancer drugs, whereas down-expression using antisense oligonucleotides conferred MDR. Ectopic expression of miR-296-3p reduced EAG1 expression and suppressed cell proliferation drug resistance, and the luciferase activity of an EAG1 3'-untranslated region-based reporter construct in U251AR cells, whereas EAG1 over-expression rescued the suppressive effect of miR-296-3p in U251AR cells. We also found that EAG1 was widely over-expressed and inversely correlated with miR-296-3p in clinical specimens. Taken together, our findings suggest that miR-296-3p may play a role of MDR in glioblastoma at least in part by targeting EAG1.

Low-complexity nonlinear adaptive filter based on a pipelined bilinear recurrent neural network.

To reduce the computational complexity of the bilinear recurrent neural network (BLRNN), a novel low-complexity nonlinear adaptive filter with a pipelined bilinear recurrent neural network (PBLRNN) is presented in this paper. The PBLRNN, inheriting the modular architectures of the pipelined RNN proposed by Haykin and Li, comprises a number of BLRNN modules that are cascaded in a chained form. Each module is implemented by a small-scale BLRNN with internal dynamics. Since those modules of the PBLRNN can be performed simultaneously in a pipelined parallelism fashion, it would result in a significant improvement of computational efficiency. Moreover, due to nesting module, the performance of the PBLRNN can be further improved. To suit for the modular architectures, a modified adaptive amplitude real-time recurrent learning algorithm is derived on the gradient descent approach. Extensive simulations are carried out to evaluate the performance of the PBLRNN on nonlinear system identification, nonlinear channel equalization, and chaotic time series prediction. Experimental results show that the PBLRNN provides considerably better performance compared to the single BLRNN and RNN models.

Synergistic effect of 14-alpha-lipoyl andrographolide and various antibiotics on the formation of biofilms and production of exopolysaccharide and pyocyanin by Pseudomonas aeruginosa.

Pseudomonas aeruginosa produces a biofilm that provides the bacteria with an effective barrier against antibiotics. Here, we investigated the synergy of various antibiotics with 14-alpha-lipoyl andrographolide (AL-1), focusing upon synthesis of the biofilm. AL-1 also inhibited the production of the exopolysaccharide and pyocyanin components. We propose that AL-1 may potentially serve as a cotherapy to combat P. aeruginosa.

A novel joint-processing adaptive nonlinear equalizer using a modular recurrent neural network for chaotic communication systems.

To eliminate nonlinear channel distortion in chaotic communication systems, a novel joint-processing adaptive nonlinear equalizer based on a pipelined recurrent neural network (JPRNN) is proposed, using a modified real-time recurrent learning (RTRL) algorithm. Furthermore, an adaptive amplitude RTRL algorithm is adopted to overcome the deteriorating effect introduced by the nesting process. Computer simulations illustrate that the proposed equalizer outperforms the pipelined recurrent neural network (PRNN) and recurrent neural network (RNN) equalizers.

Design, synthesis and antibacterial activity of novel andrographolide derivatives.

A series of andrographolide derivatives were synthesized through a facile condensation reaction with different carboxylic acids. The new compounds were characterized and screened for their antibacterial activities. A number of the new compounds significantly reduced bacterial quorum sensing virulence factors production in Pseudomonas aeruginosa, essential for pathogenesis. Compound 11b showed the best activity among all the new compounds.

Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment.

BACKGROUND: While all anti-diabetic agents can decrease blood glucose level directly or indirectly, few are able to protect and preserve both pancreatic beta cell mass and their insulin-secreting functions. Thus, there is an urgent need to find an agent or combination of agents that can lower blood glucose and preserve pancreatic beta cells at the same time. Herein, we report a dual-functional andrographolide-lipoic acid conjugate (AL-1). The anti-diabetic and beta cell protective activities of this novel andrographolide-lipoic acid conjugate were investigated. METHODS: In alloxan-treated mice (a model of type 1 diabetes), drugs were administered orally once daily for 6 days post-alloxan treatment. Fasting blood glucose and serum insulin were determined. Pathologic and immunohistochemical analysis of pancreatic islets were performed. Translocation of glucose transporter subtype 4 in soleus muscle was detected by western blot. In RIN-m cells in vitro, the effect of AL-1 on H2O2-induced damage and reactive oxidative species production stimulated by high glucose and glibenclamide were measured. Inhibition of nuclear factor kappa B (NF-kappaB) activation induced by IL-1beta and IFN-gamma was investigated. RESULTS: In alloxan-induced diabetic mouse model, AL-1 lowered blood glucose, increased insulin and prevented loss of beta cells and their dysfunction, stimulated glucose transport protein subtype 4 (GLUT4) membrane translocation in soleus muscles. Pretreatment of RIN-m cells with AL-1 prevented H2O2-induced cellular damage, quenched glucose and glibenclamide-stimulated reactive oxidative species production, and inhibited cytokine-stimulated NF-kappaB activation. CONCLUSION: We have demonstrated that AL-1 had both hypoglycemic and beta cell protective effects which translated into antioxidant and NF-kappaB inhibitory activity. AL-1 is a potential new anti-diabetic agent.