Hairy gene homolog increases nasopharyngeal carcinoma cell stemness by upregulating Bmi-1.

B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) is overexpressed in various cancer types. We found that Bmi-1 mRNA levels were elevated in nasopharyngeal carcinoma (NPC) cell lines. In immunohistochemical analyses, high Bmi-1 levels were observed in not only 5 of 38 non-cancerous nasopharyngeal squamous epithelial biopsies, but also in 66 of 98 NPC specimens (67.3%). High Bmi-1 levels were detected more frequently in T3-T4, N2-N3 and stage III-IV NPC biopsies than in T1-T2, N0-N1 and stage I-II NPC samples, indicating that Bmi-1 is upregulated in advanced NPC. In 5-8F and SUNE1 NPC cells, stable depletion of Bmi-1 using lentiviral RNA interference greatly suppressed cell proliferation, induced G1-phase cell cycle arrest, reduced cell stemness and suppressed cell migration and invasion. Likewise, knocking down Bmi-1 inhibited NPC cell growth in nude mice. Both chromatin immunoprecipitation and Western blotting assays demonstrated that Hairy gene homolog (HRY) upregulated Bmi-1 by binding to its promoter, thereby increasing the stemness of NPC cells. Immunohistochemistry and quantitative real-time PCR analyses revealed that HRY expression correlated positively with Bmi-1 expression in a cohort of NPC biopsies. These findings suggested that HRY promotes NPC cell stemness by upregulating Bmi-1, and that silencing Bmi-1 can suppress NPC progression.

MdPP2C24/37, Protein Phosphatase Type 2Cs from Apple, Interact with MdPYL2/12 to Negatively Regulate ABA Signaling in Transgenic Arabidopsis.

The phytohormone abscisic acid (ABA) plays an important role in the ability of plants to cope with drought stress. As core members of the ABA signaling pathway, protein phosphatase type 2Cs (PP2Cs) have been reported in many species. However, the functions of MdPP2Cs in apple (Malus domestica) are unclear. In this study, we identified two PP2C-encoding genes, MdPP2C24/37, with conserved PP2C catalytic domains, using sequence alignment. The nucleus-located MdPP2C24/37 genes were induced by ABA or mannitol in apple. Genetic analysis revealed that overexpression of MdPP2C24/37 in Arabidopsis thaliana led to plant insensitivity to ABA or mannitol treatment, in terms of inhibiting seed germination and overall seedling establishment. The expression of stress marker genes was upregulated in MdPP2C24/37 transgenic lines. At the same time, MdPP2C24/37 transgenic lines displayed inhibited ABA-mediated stomatal closure, which led to higher water loss rates. Moreover, when exposed to drought stress, chlorophyll levels decreased and MDA and H2O2 levels accumulated in the MdPP2C24/37 transgenic lines. Further, MdPP2C24/37 interacted with MdPYL2/12 in vitro and vivo. The results indicate that MdPP2C24/37 act as negative regulators in response to ABA-mediated drought resistance.

Coexpression Network Analysis of lncRNA Associated with Overexpression of DNMT1 in Esophageal Epithelial Cells.

Screening and preliminary identification of high DNMT1 expression-related lncRNA, which is involved in various interrelated signaling pathways, has led to the development of a theoretical basis for various types of disease mechanisms. Differential expression profiles of lncRNA and mRNA were identified in a microarray. Ten lncRNAs with high levels of variation were identified by qRT-PCR. KEGG and GO analyses were used to identify differentially expressed mRNAs. Six signaling pathways were selected based on the KEGG results of the lncRNA-mRNA expression network analysis. From the microarrays in the experimental and control groups, we found a total of 6987 differentially expressed lncRNAs, and 7421 differentially expressed mRNAs were obtained (P < 0.05; fold change > 2.0x). GO analysis and KEGG pathway analysis showed high expression of DNMT1 in esophageal epithelial cells. Nine pathways were involved in mRNA upregulation, including natural killer cell-mediated cytotoxicity and many other prominent biochemical pathways. Forty-six pathways were associated with downregulated mRNAs and ribosomes involving multiple biological pathways. Coexpression network analysis showed that 8 mRNAs and 16 lncRNAs were linked to the p53 signaling pathway. In Helicobacter pylori infections, interactions occurred between 22 lncRNAs and 11 mRNAs in the ErbB signaling pathway and between 19 lncRNAs and 8 mRNAs in epithelial cell signal transduction. Interactions were present between 19 lncRNAs and 5 mRNAs in the sphingolipid signaling pathway, along with interactions between 21 lncRNAs and 12 mRNAs in the PI3K-Akt signaling pathway. Cytotoxicity interactions occurred between 22 lncRNAs and 9 mRNAs in natural killer cells.

Boosting photoelectrochemical efficiency by near-infrared-active lattice-matched morphological heterojunctions.

Photoelectrochemical catalysis is an attractive way to provide direct hydrogen production from solar energy. However, solar conversion efficiencies are hindered by the fact that light harvesting has so far been of limited efficiency in the near-infrared region as compared to that in the visible and ultraviolet regions. Here we introduce near-infrared-active photoanodes that feature lattice-matched morphological hetero-nanostructures, a strategy that improves energy conversion efficiency by increasing light-harvesting spectral range and charge separation efficiency simultaneously. Specifically, we demonstrate a near-infrared-active morphological heterojunction comprised of BiSeTe ternary alloy nanotubes and ultrathin nanosheets. The heterojunction's hierarchical nanostructure separates charges at the lattice-matched interface of the two morphological components, preventing further carrier recombination. As a result, the photoanodes achieve an incident photon-to-current conversion efficiency of 36% at 800 nm in an electrolyte solution containing hole scavengers without a co-catalyst.

List-wise learning to rank biomedical question-answer pairs with deep ranking recursive autoencoders.

Biomedical question answering (QA) represents a growing concern among industry and academia due to the crucial impact of biomedical information. When mapping and ranking candidate snippet answers within relevant literature, current QA systems typically refer to information retrieval (IR) techniques: specifically, query processing approaches and ranking models. However, these IR-based approaches are insufficient to consider both syntactic and semantic relatedness and thus cannot formulate accurate natural language answers. Recently, deep learning approaches have become well-known for learning optimal semantic feature representations in natural language processing tasks. In this paper, we present a deep ranking recursive autoencoders (rankingRAE) architecture for ranking question-candidate snippet answer pairs (Q-S) to obtain the most relevant candidate answers for biomedical questions extracted from the potentially relevant documents. In particular, we convert the task of ranking candidate answers to several simultaneous binary classification tasks for determining whether a question and a candidate answer are relevant. The compositional words and their random initialized vectors of concatenated Q-S pairs are fed into recursive autoencoders to learn the optimal semantic representations in an unsupervised way, and their semantic relatedness is classified through supervised learning. Unlike several existing methods to directly choose the top-K candidates with highest probabilities, we take the influence of different ranking results into consideration. Consequently, we define a listwise "ranking error" for loss function computation to penalize inappropriate answer ranking for each question and to eliminate their influence. The proposed architecture is evaluated with respect to the BioASQ 2013-2018 Six-year Biomedical Question Answering benchmarks. Compared with classical IR models, other deep representation models, as well as some state-of-the-art systems for these tasks, the experimental results demonstrate the robustness and effectiveness of rankingRAE.

EPB41L3 is a potential tumor suppressor gene and prognostic indicator in esophageal squamous cell carcinoma.

Although there have been reports about the role of erythrocyte membrane protein band 4.1 like 3 (EPB41L3) in several types of cancer, primarily in non-small-cell lung carcinoma, the molecular function and modulatory mechanisms of EPB41L3 remain unclear. In specific, the functional and clinical significance of EPB41L3 in esophageal squamous cell carcinoma (ESCC) has not been explored to date. In the present study, reduced EPB41L3 expression was demonstrated in ESCC cell lines and tissues, which was due to its high methylation rate. Ectopic expression of EPB41L3 in ESCC cells inhibited cell proliferation in vivo and in vitro. In addition, EPB41L3 overexpression induced apoptosis and G2/M cell cycle arrest by activating Caspase-3/8/9 and Cyclin-dependent kinase 1/Cyclin B1 signaling, respectively. Notably, patients with higher EPB41L3 expression had markedly higher overall survival rates compared with patients with lower EPB41L3 expression. In summary, the present results suggest that EPB41L3 may be a tumor suppressor gene in ESCC development, representing a potential therapeutic target and a prognostic indicator for ESCC.

Epb41l3 suppresses esophageal squamous cell carcinoma invasion and inhibits MMP2 and MMP9 expression.

EPB41L3 may play a role as a metastasis suppressor by supporting regular arrangements of actin stress fibres and alleviating the increase in cell motility associated with enhanced metastatic potential. Downregulation of epb41l3 has been observed in many cancers, but the role of this gene in esophageal squamous cell carcinoma (ESCC) remains unclear. Our study aimed to determine the effect of epb41l3 on ESCC cell migration and invasion. We investigated epb41l3 protein expression in tumour and non-tumour tissues by immunohistochemical staining. Expression in the non-neoplastic human esophageal cell line Het-1a and four ESCC cell lines - Kyse150, Kyse510, Kyse450 and Caes17 - was assessed by quantitative Polymerase Chain Reaction (qPCR) and Western blotting. Furthermore, an EPB41L3 overexpression plasmid and EPB41L3-specific small interfering RNA were used to upregulate EPB41L3 expression in Kyse150 cells and to downregulate EPB41L3 expression in Kyse450 cells, respectively. Cell migration and invasion were evaluated by wound healing and transwell assays, respectively. The expression levels of p-AKT, matrix metalloproteinase (MMP)2 and MMP9 were evaluated. Expression of epb41l3 was significantly lower in tumour tissues than in non-tumour tissues and in ESCC cell lines compared with the Het-1a cell line. Kyse450 and Caes17 cells exhibited higher expression of epb41l3 than Kyse150 and Kyse510 cells. Overexpressing epb41l3 decreased Kyse150 cell migration and invasion, whereas EPB41L3-specific small interfering RNA silencing increased these functions in Kyse450 cells. Furthermore, overexpressing epb41l3 led to downregulation of MMP2 and MMP9 in Kyse150 and Kyse510 cells. Our findings reveal that EPB41L3 suppresses tumour cell invasion and inhibits MMP2 and MMP9 expression in ESCC cells.

UDP-glucosyltransferase71c5, a major glucosyltransferase, mediates abscisic acid homeostasis in Arabidopsis.

Abscisic acid (ABA) plays a key role in plant growth and development. The effect of ABA in plants mainly depends on its concentration, which is determined by a balance between biosynthesis and catabolism of ABA. In this study, we characterize a unique UDP-glucosyltransferase (UGT), UGT71C5, which plays an important role in ABA homeostasis by glucosylating ABA to abscisic acid -: glucose ester (GE) in Arabidopsis (Arabidopsis thaliana). Biochemical analyses show that UGT71C5 glucosylates ABA in vitro and in vivo. Mutation of UGT71C5 and down-expression of UGT71C5 in Arabidopsis cause delay in seed germination and enhanced drought tolerance. In contrast, overexpression of UGT71C5 accelerates seed germination and reduces drought tolerance. Determination of the content of ABA and ABA-GE in Arabidopsis revealed that mutation in UGT71C5 and down-expression of UGT71C5 resulted in increased level of ABA and reduced level of ABA-GE, whereas overexpression of UGT71C5 resulted in reduced level of ABA and increased level of ABA-GE. Furthermore, altered levels of ABA in plants lead to changes in transcript abundance of ABA-responsive genes, correlating with the concentration of ABA regulated by UGT71C5 in Arabidopsis. Our work shows that UGT71C5 plays a major role in ABA glucosylation for ABA homeostasis.

Quasi-unidirectional shrinkage of gels with well-oriented lipid bilayers upon uniaxial stretching.

PDGI-PAAm gels with well oriented lipid bilayers show a quasi-unidirectional shrinkage upon uniaxial stretching along the bilayers. They shrink largely parallel to the bilayer but slightly perpendicular to it in order not to increase the bilayer area and its interfacial energy. Such an anisotropic deformation can be well-modelled based on classical theories for gel networks and lipid layers.

A novel membrane-bound E3 ubiquitin ligase enhances the thermal resistance in plants.

High temperature stress disturbs cellular homoeostasis and results in a severe retardation in crop growth and development. Thus, it is important to reveal the mechanism of plants coping with heat stress. In this study, a novel gene that we identified from Brassica napus, referred to as BnTR1, was found to play a key role in heat stress response in planta. BnTR1 is a membrane-bound RINGv (C4HC3) protein that displays E3 ligase activity in vitro. We demonstrated that modest expression of BnTR1 is sufficient to minimize adverse environmental influence and confers thermal resistance on development without any detrimental effects in B. napus and Oryza sativa. Our investigation into the action mechanism indicates that BnTR1 is likely to be involved in mediating Ca²âº dynamics by regulating the activity of calcium channels, which further alters the transcripts of heat shock factors and heat shock proteins contributing to plant thermotolerance. Hence, our study identified BnTR1 as a novel key factor underlying a conserved mechanism conferring thermal resistance in plants.

[Construction and identification of blood type B antigen mimetic polypeptide-Mip3beta double expression recombinant plasmid].

OBJECTIVE: To construct and identify blood type B antigen mimetic polypeptide-macrophage inflammatory protein 3beta (Mip3beta) double expression recombinant plasmid. METHODS: The positive phage clone P1 was obtained using phage random 12-mer peptide library. Specific primers were designed to amplify the phage DNA of P1 and transmembrane domain and inner segment of PBluscript-Fas gene. The products of the amplification were linked into Mip3betav21 to construct blood type B antigen mimetic polypeptide-Mip3beta double expression recombinant plasmid. The recombinant plasmid was transfected into human melanoma cell line B16 to identify its expression. RESULTS AND CONCLUSION: Blood type B antigen mimetic polypeptide-Mip3beta double expression recombinant plasmid is successfully obtained and expressed in human melanoma cell line B16.

[Efficacy of cryoablation combined with CpG oligonucleotides in the treatment of murine transplanted colon carcinoma].

OBJECTIVE: To investigate the efficacy of cryoablation combined with CpG ODN in the treatment of murine transplanted colon carcinoma. METHODS: Colon carcinoma model was established by subcutaneously inoculating CT26 cells into the right flank in BALB/c mice. The tumor-bearing mice were randomly divided into 4 groups:the group of PBS injected in peritumoral area, the group of cryoablation, the group of cryoablation combined with CpG ODN, the group of CpG ODN injected in peritumoral area. The tumor size changes were measured. Serum levels of interleukin (IL)-12 and interferon-gamma(IFN-gamma) were assayed by ELISA. The rates of CD3(+)CD4(+)T, CD3(+)CD8(+)T lymphocytes in serum were counted with flow cytometry. Mice in the cryoablation group and the combined group with tumor regression were re-challenged with CT26 cells. RESULTS: The survival time of cryoablation group and combined therapy group were (80.3 + or - 5.4) days and (83.8 + or - 5.5) days, respectively, longer than (53.7 + or - 3.7) days in PBS group and (51.5 + or - 6.8) days in CpG ODN group(all P<0.05). The suppress rates of tumor cells in cryoablation group and combined therapy group were 83.8% and 86.2% respectively. After 20 days following treatment, CD3(+)CD4(+)T/CD3(+)CD8(+)T ratio and the concentrations of IL-12 and IFN-gamma in mice serum of cryoablation group and combined therapy group were higher than those in PBS group and CpG ODN group(all P<0.05). No significant difference was found in CD3(+)CD4(+)T/CD3(+)CD8(+)T ratio between cryoablation group and combined therapy group(P>0.05). However, the concentrations of IL-12 and IFN-gamma in combined therapy group were higher than those of cryoablation group(all P<0.05). After re-challenging, tumor formation rate in the cryoablation combined with CpG ODN group was 16.7%, significantly lower than that in the cryoablation group(83.8%)(P<0.05). CONCLUSION: Cryoablation combined with CpG ODN can increase antitumor immune response in mice, and therefore can decrease the tumor formation when re-challenged with CT26 cells.

[Therapeutic and immunological effects of microwave ablation combined with CpG ODN on transplanted colon carcinoma in mice].

OBJECTIVE: To investigate the therapeutic and immunological effects of microwave ablation (MA) combined with CpG ODN in mice bearing transplanted colon carcinoma. METHODS: A mouse model bearing colon carcinoma was established by subcutaneously inoculating CT26 cells into the right flank of Balb/c mice. The tumor-bearing mice were randomized into control group with PBS injection in the peritumoral area, MA group, MA combinated with CpG ODN group, and CpG ODN group with CpG ODN injection in the peritumoral area. The tumor volume changes were observed, and serum CD3(+)CD4(+) and CD3(+)CD8(+) T lmyphocytes were analyzed by flow cytometry after the treatments. Serum levels of interleukin (IL)-2, IL-12 and IFN-gamma were detected by ELISA. The mice in the MA group and the combined treatment group showing tumor regression were rechallenged with CT26 cells. RESULTS: No significant difference was found in the number of serum CD3(+), CD3(+)CD4(+), or CD3(+)CD8(+) T lymphocytes between the 4 groups. The ratio of CD3(+)CD4(+)/CD3(+)CD8(+) T lymphocytes in the combined treatment group and MA group were 1.58-/+0.10 and 1.53-/+0.13, respectively, significantly higher than that in PBS group and CpG ODN group (P<0.05). The serum concentration of IL-2, IL-12 and IFN-gamma in the combined treatment group were 64.6-/+7.4 pg/ml, 314.1-/+26.9 pg/ml and 61.9-/+7.3 pg/ml, respectively, significantly higher than those in the other 3 groups (P<0.05). The tumor formation rate in the combined treatment group was significantly lower than that in MA group (25.0% vs 75.0%, P<0.05). CONCLUSION: CpG ODN can enhance the immunity and decrease the tumor formation rate following a rechallenge with CT26 cells in mice treated with MA.

Effects of permethrin, cypermethrin and 3-phenoxybenzoic acid on rat sperm motility in vitro evaluated with computer-assisted sperm analysis.

Pyrethroid pesticides, produced and used worldwide, have been reported to impair male reproductive function by reducing sperm count and sperm motility. They are divided into two types: type I pyrethroids including permethrin, etc. and type II pyrethroids including cypermethrin, fenvalerate, cyfluthrin, etc. Our previous study showed that fenvalerate and cypermethrin could reduce sperm motility in vitro. However, it is not clear whether permethrin and 3-phenoxybenzoic acid (3-PBA, the major metabolite of pyrethroids) affect sperm motility directly or indirectly by affecting spermatogenesis via interaction with androgens and/or their receptors. In this study, rat sperm suspensions were treated respectively with permethrin, cypermethrin and 3-PBA, at various concentrations (0, 1, 4, 16, or 64mmol/L) for various times (1, 2, or 4h). The motility parameters of sperm were analyzed with a computer-assisted sperm analysis (CASA) system. The differential effects of permethrin and cypermethrin on sperm motility patterns in vitro were also compared. Our study revealed that permethrin and cypermethrin could reduce sperm motility in vitro in a concentration- and time-dependent manner. Marked differences between the two pyrethroids were not found in this study. Moreover, 3-PBA did not reduce sperm motility directly at all concentrations and treatment periods. These results provide further evidence that permethrin and cypermethrin can directly affect mature rat sperm motility.

Intra-tumor injection of H101, a recombinant adenovirus, in combination with chemotherapy in patients with advanced cancers: a pilot phase II clinical trial.

AIM: H101, an E1B 55 kD gene deleted adenovirus, has been shown to possess oncolysis activity experimentally and proved to be safe in preliminary phase I study. The current study was designed to evaluate its anti-tumor activity and toxicity in combination with chemotherapy in patients with late stage cancers. METHODS: H101 5.0x10(11) virus particles were given by intra-tumor injection daily for five consecutive days at every three-week cycle, combined with routine chemotherapy, to one of the tumor lesions of 50 patients with different malignant tumors. Tumor lesions without H101 injection in the same individuals were used as controls. The efficacy and toxicity were recorded. RESULTS: Forty-six patients were evaluable with a 30.4% response rate. H101 injection in combination with chemotherapy induced three complete response (CR) and 11 partial response (PR), giving an overall response rate of 28.0% (14/50) among intention-to-treat patients. The response rate for the control lesions was 13.0%, including one case with CR and five cases with PR, which was significantly lower than that for the injected lesions (P<0.05). Main side effects were fever (30.2%) and pain at the injected sites (26.9%). Grade 1 hepatic dysfunction was found in four patients, grade 2 in one patient, and grade 4 in one patient. Hematological toxicity (grade 4) was found in four patients. CONCLUSION: Intra-tumor injection of the genetically engineered adenovirus H101 exhibits potential anti-tumor activity to refractory malignant tumors in combination with chemotherapy. Low toxicity and good tolerance of patients to H101were observed.

[Morphology, cytogenetics of intergeneric hybrid between Aegilops taucchii and Dasypyrum villosum].

"Aegilops tauschii x Dasypyrum villosum" F1 hybrids were obtained by the combination of hybridization and embryo culture in vitro. Chromosome pairing behavior in meiosis of the hybrid F1 was carried out. Results showed that in an average , 1.25 rod bivalents were observed in one PMC, meiotic configuration was 2n=14=11.49 I + 1.25 II (Xta=1.25) and most of PMCs possessed 1 approximately 5(rod) bivalens, indicating that the relatively high homeology was detected between the D genome of Ae. tauschii and the V genome of D. villosum. The morphological differences between F1 hybrids and their parents were significant. F1 plants were highly self-sterile, but partially self-fertile after treated by chromosome doubling technique.