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Cancer and its associated conditions have significant impacts on public health at many levels worldwide, and cancer is the leading cause of death among adults. Peroxisome proliferator-activated receptor α (PPARα)-specific agonists, fibrates, have been approved by the Food and Drug Administration for managing hyperlipidemia. PPARα-specific agonists exert anti-cancer effects in many human cancer types, including glioblastoma (GBM). Recently, we have reported that the hypoxic state in GBM stabilizes hypoxia-inducible factor-1 alpha (HIF-1α), thus contributing to tumor escape from immune surveillance by activating the expression of the pH-regulating protein carbonic anhydrase IX (CA9). In this study, we aimed to study the regulatory effects of the PPARα agonist fibrate on the regulation of HIF-1α expression and its downstream target protein in GBM. Our findings showed that fenofibrate is the high potency compound among the various fibrates that inhibit hypoxia-induced HIF-1α and CA9 expression in GBM. Moreover, fenofibrate-inhibited HIF-1α expression is mediated by HO-1 activation in GBM cells through the AMP-activated protein kinase (AMPK) pathway. In addition, fenofibrate-enhanced HO-1 upregulation activates SIRT1 and leads to subsequent accumulation of SIRT1 in the nucleus, which further promotes HIF-1α deacetylation and inhibits CA9 expression. Using a protein synthesis inhibitor, cycloheximide, we also observed that fenofibrate inhibited HIF-1α protein synthesis. In addition, the administration of the proteasome inhibitor MG132 showed that fenofibrate promoted HIF-1α protein degradation in GBM. Hence, our results indicate that fenofibrate is a useful anti-GBM agent that modulates hypoxia-induced HIF-1α expression through multiple cellular pathways.

Background: We describe a DNA methylation assay, named MPap test, using cervical scraping as an alternative technique for endometrial cancer detection. Methods: A multicenter hospital-based, two-stage validation study was conducted to validate the cancer detection performance of the MPap test. The MPap value was determined from the DNA methylation status of two genes (BHLHE22, CDO1) and combined with two other clinical variables (age, BMI). The cutoff threshold of the MPap value was established in stage 1 and validated in stage 2. A total of 592 women with abnormal uterine bleeding were enrolled from five medical centers throughout Taiwan. Results: In stage 1, the sensitivity, specificity, and positive and negative predictive values of the MPap test for detecting endometrial cancer were 92.9%, 71.5%, 39.8%, and 98.0%, respectively. These values were validated in stage 2, being 92.5%, 73.8%, 40.2%, and 98.1%. Moreover, MPap outperformed transvaginal ultrasound in sensitivity and negative predictive values for detecting endometrial cancer. When we applied the algorithm for triage of endometrial cancer detection by MPap in the Taiwan National Health Insurance dataset, we found that it may reduce invasive procedures by 69~73%. Conclusions: MPap may provide a feasible alternative for endometrial cancer detection and can be considered as a triage test to reduce unnecessary invasive procedures.

Since the first report of SARS-CoV-2 in December 2019, Taiwan has gone through three local outbreaks. Unlike the first two outbreaks, the spatial and temporal origin of the third outbreak (April 20 to November 5, 2021) is still unclear. We assembled and analyzed a data set of more than 6,000 SARS-CoV-2 genomes, including 300 from Taiwan and 5812 related sequences downloaded from GISAID as of 2021/12/08. We found that the third outbreak in Taiwan was caused by a single virus lineage belonging to Alpha (B.1.1.7) strain. This lineage, T-III (the third outbreak in Taiwan), carries a distinct genetic fingerprint, consisting of spike M1237I (S-M1237I) and three silent mutations, C5812T, C15895T, and T27869C. The T-III is closest to the sequences derived from Turkey on February 8, 2021. The estimated age of the most recent common ancestor (TMRCA) of T-III is March 23, 2021 (95% highest posterior density [HPD] February 24 - April 13, 2021), almost one month before the first three confirmed cases on April 20, 2021. The effective population size of the T-III showed approximately 20-fold increase after the onset of the outbreak and reached a plateau in early June 2021. Our results reconcile several unresolved observations, including the occurrence of two infection clusters at the same time without traceable connection and several airline pilots who were PCR negative but serum IgM-/IgG+ for SARS-CoV-2 in late April. Therefore, in contrast to the general notion that the third SARS-CoV-2 outbreak in Taiwan was sparked by two imported cases from USA on April 20, 2021, which, in turn, was caused by the partial relaxation of entry quarantine measures in early April 2021, our comprehensive analyses demonstrated that the outbreak was most likely originated from Europe in February 2021.

Bulk-fill resin-based composites (RBCs) are a new class of restorative materials, and polymerization shrinkage (PS) is concerned due to their single increment up to 4 mm. The aim of this study was to evaluate the PS and shrinkage stress (SS) of bulk-fill RBCs in vitro.Three bulk-fill RBCs and three conventional non-bulk-fill RBCs were selected. The PS was determined with Acuvol volumetric shrinkage analyzer by calculating the specimen volume variation before and after light irradiation. The SS was investigated using universal testing machine method with a polymethyl methacrylate rod as a bonding substrate. The force generated during the polymerization process was detected by a load cell linked to a computer. SS was calculated by dividing the maximum stress force by the area of the rod.The mean PS of various RBCs ranged from 1.72% to 2.13%. All PS results of bulk-fill RBCs were comparable to their conventional counterparts. Sonicfill 2 (SF2) and Harmonize (HM) showed the lowest PS (p 0.05; Tukey HSD test). Medians of SS results ranged from 0.55 MPa to 0.67 MPa. All SSs of bulk-fill RBCs were comparable to their conventional counterparts. SF2 showed significantly lower SS than Tetric N-Ceram (TN) and Tetric N-Ceram Bulk Fill (TNB) (p 0.0083; post hoc comparisons with Bonferroni adjustments). A moderate, positive correlation was observed between PS and SS with Pearson's correlation (r = 0.446, p = 0.013).Both PS and SS are material dependent. A moderate, positive correlation between PS and SS is found with new bulk-fill RBCs and their conventional counterparts.

Cancer has been considered a metabolic disease in recent years. Compared to normal cells, cancer cells rewire metabolic pathways to sustain their outgrowth. While growing fast, cancer cells in the core region of a solid tumor encounter metabolic stress induced by hypoxia and insufficient nutrition, and mitochondrial dynamics has a profound effect on the survival of cancer cells. However, how mitochondrial dynamics affects cancer cell survival under metabolic stress has not been fully elucidated. Krüppel-associated box-associated protein-1 (KAP1), also known as TRIM28, is a transcriptional co-regulator participating in multiple cellular physiological processes. The post-translational modifications of KAP1 play an essential role in regulating its function. We have previously demonstrated that KAP1 mRNA is highly expressed in concomitant with the upregulation of genes involving in glycolysis and oxidative phosphorylation in breast cancer. Furthermore, KAP1 is phosphorylated at Serine 473 (pS473) upon the induction of nutrient stresses via reactive oxygen species (ROS)-p38 MAPK signaling in breast cancer cells. The S473 phosphorylation of KAP1 reduces the expression of mitochondrial outer membrane protein mitofusin 2 (MFN2), which prevents the hyperfusion of mitochondria and the overproduction of ROS under nutrient deprivation. However, the mechanism of how KAP1 regulates the expression of MFN2 remains unclear. We have engineered a KAP1-deficient MDA-MB-231 cell line and re-expressed KAP1 S473 wild-type (WT), S473A (phosphorylation-defective) or S473D (phosphorylation-mimic) mutants. By analyzing the mRNA expression profiles from these cell lines, several microRNAs (miRNAs) were shown to be upregulated in the KAP1 S473D-expressing cells, which implied that pS473-KAP1 may regulate MFN2 expression through miRNA. Using several miRNA target prediction algorithms, miR-20b was predicted to target the 3’-untranslated region (UTR) of MFN2 mRNA, and the sequence of target site was conserved through evolution. By performing MFN2 3’UTR dual luciferase reporter assays, we have confirmed that MFN2 3’UTRwas targeted by miR-20b and regulated by the phosphorylation status at S473 of KAP1. Also, miR-20b expression was upregulated upon glucose deprivation and both MFN2 mRNA and protein levels declined in breast cancercells overexpressed with miR-20b mimics. In addition, KAP1 S473D, rather than S473A-expressing cells produced more miR-20b under glucose depletion condition and MFN2 expression levels were inversely correlated with miR-20b expression. Moreover, the analysis of The Cancer Genome Atlas (TCGA) breast tumor datasets indicated that there was higher miR-20b but lower MFN2 expression in advanced breast tumors compared with the primary tumors and normal tissues. In conclusion, these results suggested that the induction of KAP1 S473 phosphorylation under nutrition deprivation inhibited MFN2 by upregulating miR-20b, which prevented mitochondrial hyperfusion and consequently benefited breast cancer cell survival in response to metabolic stress. Citation Format: Yu-Shu Liu, Chun-Ting Cheng, Ching Ouyang, Ge-Jyun Liu, David Kong Ann, Ching-Ying Kuo. Phosphorylation of KAP1 Serine 473 regulates mitochondrial dynamics through miR-20b under metabolic stress in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-03.

Simple Summary The present study showed that a prescribed psychotropic medicine paliperidone inhibits GBM growth and prolongs survival in mouse brain tumor model and decreased the programmed death ligand 1 expression. Using the 3D co-culture also found that dopamine receptor D2 regulates the interaction of GBM-macrophage-induced PD-L1 expression in GBMs. In addition, the expression of DRD2 and PD-L1 in GBM modulates tumor-associated macrophage polarization. Our results also indicated that there is a contact-independent mechanism of PD-L1 induction in GBM upon interaction between GBM and monocytes. The present study also found that the interaction of GBM-macrophage-enhanced PD-L1 expression in GBM occurred by modulating the ERK and STAT3 signaling pathways. In addition, the inhibition of DRD2 reduces the upregulation of PD-1 expression, and it is regulating signaling in GBM. Abstract A previous study from our group reported that monocyte adhesion to glioblastoma (GBM) promoted tumor growth and invasion activity and increased tumor-associated macrophages (TAMs) proliferation and inflammatory mediator secretion as well. The present study showed that prescribed psychotropic medicine paliperidone reduced GBM growth and immune checkpoint protein programmed death ligand (PD-L)1 expression and increased survival in an intracranial xenograft mouse model. An analysis of the database of patients with glioma showed that the levels of PD-L1 and dopamine receptor D (DRD)2 were higher in the GBM group than in the low grade astrocytoma and non-tumor groups. In addition, GFP expressing GBM (GBM-GFP) cells co-cultured with monocytes-differentiated macrophage enhanced PD-L1 expression in GBM cells. The enhancement of PD-L1 in GBM was antagonized by paliperidone and risperidone as well as DRD2 selective inhibitor L741426. The expression of CD206 (M2 phenotype marker) was observed to be markedly increased in bone marrow-derived macrophages (BMDMs) co-cultured with GBM. Importantly, treatment with paliperidone effectively decreased CD206 and also dramatically increased CD80 (M1 phenotype marker) in BMDMs. We have previously established a PD-L1 GBM-GFP cell line that stably expresses PD-L1. Experiments showed that the expressions of CD206 was increased and CD80 was mildly decreased in the BMDMs co-cultured with PD-L1 GBM-GFP cells. On the other hands, knockdown of DRD2 expression in GBM cells dramatically decreased the expression of CD206 but markedly increased CD80 expressions in BMDMs. The present study suggests that DRD2 may be involved in regulating the PD-L1 expression in GBM and the microenvironment of GBM. Our results provide a valuable therapeutic strategy and indicate that treatments combining DRD2 antagonist paliperidone with standard immunotherapy may be beneficial for GBM treatment.

Aluminum (Al) toxicity is a major limitation to crop production in countries where acidic soil is abundant. In China, soybean production is constrained by Al stress-induced toxicity. As such, there is growing interest to develop Al-resistant varieties. In the present study, we sought to determine potential genes, functions and pathways for screening and breeding of Al-resistant varieties of soybean. First, we mined the E-GEOD-18517 dataset and identified 729 differentially expressed genes (DEGs) between untreated and Al-treated groups. Next, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathways enrichment analysis and observed that most of the screened genes were mainly enriched in defense response, plasma membrane and molecular transducer activity. They were also enriched in three important pathways, the phenylpropanoid biosynthesis, plant-pathogen interaction, and cutin, suberine and wax biosynthesis. Utilizing weighted gene co-expression network analysis of 815 DEGs screened by Venn diagram, we identified DEGs that were the most disparate between treated and untreated groups. LOC100793667 (probable protein phosphatase 2C 60, GLYMA_17G223800), LOC100780576 (ethylene-responsive transcription factor 1B, GLYMA_02G006200), and LOC100785578 (protein ESKIMO 1, GLYMA_02G258000) were the most differentially expressed, which were consistent with the qRT-PCR results. As these genes are known to participate in essential functions, such as cell junction and phenylpropanoid biosynthesis, these genes may be important for breeding Al-resistant varieties. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01018-x.

Glioblastoma (GBM) is the most common and lethal brain tumor with high inflammation. GBM cells infiltrate microglia and macrophages and are surrounded by pro-inflammatory cytokines. Interleukin (IL)-1β, which is abundantly expressed in the tumor microenvironment, is involved in tumor progression. Intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 mediate cell-cell interactions, and these cell adhesion molecules (CAMs) can be regulated by cytokines in immune cells or cancer cells in the inflammatory tumor microenvironment. In this study, we found that ICAM-1 and VCAM-1 expression was induced when GBM cells were treated with IL-1β, and that adhesive interaction between monocytes and GBM cells increased accordingly. The levels of soluble CAMs (sICAM-1 and sVCAM-1) were also increased in the supernatants induced by IL-1β. Furthermore, the conditioned media contained sICAM-1 and sVCAM-1, which further promoted IL-6 and CCL2 expression in differentiated macrophages. IL-1β downregulated Src homology 1 domain-containing protein tyrosine phosphatase (SHP-1) in GBM. The expression of ICAM-1 and VCAM-1 was regulated by p38, AKT, and NF-κB signaling pathways, which were modulated by SHP-1 signaling. The present study suggests that IL-1β-induced protein expression of ICAM-1 and VCAM-1 in GBM may modulate the adhesive interaction between GBM and monocytes. In addition, IL-1β also induced the soluble form of ICAM-1 and VCAM-1 in GBM, which plays a key role in the regulation of tumor-associated monocyte/macrophage polarization.

Carbonic anhydrases (CAs) are acid&ndash, base regulatory proteins that modulate a variety of physiological functions. Recent findings have shown that CAIX is particularly upregulated in glioblastoma multiforme (GBM) and is associated with a poor patient outcome and survival rate. An analysis of the GSE4290 dataset of patients with gliomas showed that CAIX was highly expressed in GBM and was negatively associated with prognosis. The expression of CAIX under hypoxic conditions in GBM significantly increased in protein, mRNA, and transcriptional activity. Importantly, CAIX upregulation also regulated GBM motility, monocyte adhesion to GBM, and the polarization of tumor-associated monocytes/macrophages (TAM). Furthermore, the overexpression of CAIX was observed in intracranial GBM cells. Additionally, epidermal growth factor receptor/signal transducer and activator of transcription 3 regulated CAIX expression under hypoxic conditions by affecting the stability of hypoxia-inducible factor 1&alpha, In contrast, the knockdown of CAIX dramatically abrogated the change in GBM motility and monocyte adhesion to GBM under hypoxic conditions. Our results provide a comprehensive understanding of the mechanisms of CAIX in the GBM microenvironment. Hence, novel therapeutic targets of GBM progression are possibly developed.

Glioblastoma (GBM), the most aggressive brain tumor, has a poor prognosis due to the ease of migration to surrounding healthy brain tissue. Recent studies have shown that bradykinin receptors are involved in the progression of various cancers. However, the molecular mechanism and pathological role of bradykinin receptors remains unclear. We observed the expressions of two major bradykinin receptors, B1R and B2R, in two different human GBM cell lines, U87 and GBM8901. Cytokine array analysis showed that bradykinin increases the production of interleukin (IL)-8 in GBM via B1R. Higher B1R levels correlate with IL-8 expression in U87 and GBM8901. We observed increased levels of phosphorylated STAT3 and SP-1 in the nucleus as well. Using chromatin immunoprecipitation assay, we found that STAT3 and SP-1 mediate IL-8 expression, which gets abrogated by the inhibition of FAK and STAT3. We further demonstrated that IL-8 expression and cell migration are also regulated by the SP-1. In addition, expression levels of STAT3 and SP-1 positively correlate with clinicopathological grades of gliomas. Interestingly, our results found that inhibition of HDAC increases IL-8 expression. Moreover, stimulation with bradykinin caused increases in acetylated SP-1 and p300 complex formation, which are abrogated by inhibition of FAK and STAT3. Meanwhile, knockdown of SP-1 and p300 decreased the augmentation of bradykinin-induced IL-8 expression. These results indicate that bradykinin-induced IL-8 expression is dependent on B1R which causes phosphorylated STAT3 and acetylated SP-1 to translocate to the nucleus, hence resulting in GBM migration.

Buckling Restrained Braces (BRBs) are effective energy dissipation devices. The key advantages of BRB are its comparable tensile and compressive behavior and stable energy dissipation capacity. In this paper, low-cycle fatigue performance of domestic BRBs is obtained based on collected experimental data under constant and variable amplitude loadings. The results show that the relationship between fatigue life and strain amplitude satisfies the Mason-Coffin equation. By adopting theory of structural reliability, this paper presents several allowable fatigue life curves with different confidential levels. Besides, Palmgren-Miner method was used for calculating BRB cumulative damages. An allowable damage factor with 95% confidential level is put forward for assessing damage under variable amplitude fatigue. In addition, this paper presents an empirical criterion with rain flow algorithm, which may be used to predict the fracture of BRBs under severe earthquakes and provide theory and method for their engineering application. Finally, the conclusions of the paper were vilified through precise yet conservative prediction of the fatigue failure of BRB.

Tumor-associated macrophages (TAMs) originate as circulating monocytes, and are recruited to gliomas, where they facilitate tumor growth and migration. Understanding the interaction between TAM and cancer cells may identify therapeutic targets for glioblastoma multiforme (GBM). Vascular cell adhesion molecule-1 (VCAM-1) is a cytokine-induced adhesion molecule expressed on the surface of cancer cells, which is involved in interactions with immune cells. Analysis of the glioma patient database and tissue immunohistochemistry showed that VCAM-1 expression correlated with the clinico-pathological grade of gliomas. Here, we found that VCAM-1 expression correlated positively with monocyte adhesion to GBM, and knockdown of VCAM-1 abolished the enhancement of monocyte adhesion. Importantly, upregulation of VCAM-1 is dependent on epidermal-growth-factor-receptor (EGFR) expression, and inhibition of EGFR effectively reduced VCAM-1 expression and monocyte adhesion activity. Moreover, GBM possessing higher EGFR levels (U251 cells) had higher VCAM-1 levels compared to GBMs with lower levels of EGFR (GL261 cells). Using two- and three-dimensional cultures, we found that monocyte adhesion to GBM occurs via integrin α4β1, which promotes tumor growth and invasion activity. Increased proliferation and tumor necrosis factor-α and IFN-γ levels were also observed in the adherent monocytes. Using a genetic modification approach, we demonstrated that VCAM-1 expression and monocyte adhesion were regulated by the miR-181 family, and lower levels of miR-181b correlated with high-grade glioma patients. Our results also demonstrated that miR-181b/protein phosphatase 2A-modulated SP-1 de-phosphorylation, which mediated the EGFR-dependent VCAM-1 expression and monocyte adhesion to GBM. We also found that the EGFR-dependent VCAM-1 expression is mediated by the p38/STAT3 signaling pathway. Our study suggested that VCAM-1 is a critical modulator of EGFR-dependent interaction of monocytes with GBM, which raises the possibility of developing effective and improved therapies for GBM.

Glioblastoma (GBM) is characterized by severe hypoxic and acidic stress in an abnormal microenvironment. Monocarboxylate transporter (MCT)4, a pH-regulating protein, plays an important role in pH homeostasis of the glycolytic metabolic pathways in cancer cells. The present study showed that GBM exposure to hypoxic conditions increased MCT4 expression. We further analyzed the glioma patient database and found that MCT4 was significantly overexpressed in patients with GBM, and the MCT4 levels positively correlated with the clinico-pathological grades of gliomas. We further found that MCT4 knockdown abolished the hypoxia-enhanced of GBM cell motility and monocyte adhesion. However, the overexpression of MCT4 promoted GBM cell migration and monocyte adhesion activity. Our results also revealed that MCT4-regulated GBM cell motility and monocyte adhesion are mediated by activation of the serine/threonine-specific protein kinase (AKT), focal adhesion kinase (FAK), and epidermal growth factor receptor (EGFR) signaling pathways. Moreover, hypoxia mediated the acetylated signal transducer and activator of transcription (STAT)3 expression and regulated the transcriptional activity of hypoxia inducible factor (HIF)-1&alpha, in GBM cell lines. In a GBM mouse model, MCT4 was significantly increased in the tumor necrotic tissues. These findings raise the possibility for the development of novel therapeutic strategies targeting MCT4.

Ethylene-response factor (ERF) proteins are members of a transcription factor family involved in plant growth and environmental stress responses, but the biological functions of ERF members in adzuki bean (Vigna angularis var. angularis) remain unknown. In addition, it is unclear whether these proteins have a role in regulating responses to abiotic stressors. Here, we identified 47 ERF genes by analyzing the adzuki bean genome. Whole-transcriptome analyses of plants under saline-alkaline stress suggested that the expression of 13 ERF genes was induced in response to saline-alkaline stress. Analysis of the cis-acting elements showed that the promoters of these saline-alkaline stress-inducible ERF genes contained LTRs, DREs, MYBs, ABREs, MYCs, CGTCA-, and TGACG-motifs, which are involved in abiotic stress responses. The expression of VaERF3 was induced by NaHCO3, polyethylene glycol 6000, NaCl, and ABA (abscisic acid), as determined by qRT-PCR. Overexpression of VaERF3 in transgenic Arabidopsis resulted in higher levels of proline accumulation and lower malondialdehyde and reactive oxygen species contents in plants grown under saline-alkaline stress conditions. Moreover, VaERF3 encoded a nuclear-localized transcriptional activator that promoted the expression of stress-responsive genes. Collectively, these results are of great significance in elucidating the mechanisms of saline-alkaline stress responses in adzuki bean.

Natural products have historically been regarded as an important resource of therapeutic agents. Resveratrol and melatonin have been shown to increase SIRT1 activity and stimulate deacetylation. Glioblastoma multiforme (GBM) is the deadliest of malignant types of tumor in the central nervous system (CNS) and their biological features make treatment difficult. In the glioma microenvironment, infiltrating immune cells has been shown to possess beneficial effects for tumor progression. We analyzed SIRT1, CCL2, VCAM-1 and ICAM-1 in human glioma cell lines by immunoblotting. The correlation between those markers and clinico-pathological grade of glioma patients were assessed by the Gene Expression Omnibus (GEO) datasets analysis. We also used monocyte-binding assay to study the effects of melatonin on monocyte adhesion to GBM. Importantly, overexpression of SIRT1 by genetic modification or treatment of melatonin significantly downregulated the adhesion molecular VCAM-1 and ICAM-1 expression in GBM. CCL2-mediated monocyte adhesion and expression of VCAM-1 and ICAM-1 were regulated through SIRT1 signaling. SIRT1 is an important modulator of monocytes interaction with GBM that gives the possibility of improved therapies for GBM. Hence, this study provides a novel treatment strategy for the understanding of microenvironment changes in tumor progression.

Glioblastoma (GBM) is the most commonly occurring tumor in the cerebral hemispheres. Currently, temozolomide (TMZ), an alkylating agent that induces DNA strand breaks, is considered the frontline chemotherapeutic agent for GBM. Despite its frontline status, GBM patients commonly exhibit resistance to TMZ treatment. We have recently established and characterized TMZ-resistant human glioma cells. The aim of this study is to investigate whether curcumin modulates cell apoptosis through the alternation of the connexin 43 (Cx43) protein level in TMZ-resistant GBM. Overexpression of Cx43, but not ATP-binding cassette transporters (ABC transporters), was observed (approximately 2.2-fold) in TMZ-resistant GBM cells compared to the Cx43 levels in parental GBM cells. Furthermore, at a concentration of 10[Formula: see text][Formula: see text]M, curcumin significantly reduced Cx43 protein expression by about 40%. In addition, curcumin did not affect the expression of other connexins like Cx26 or epithelial-to-mesenchymal transition (EMT) proteins such as [Formula: see text]-catenin or [Formula: see text]E-catenin. Curcumin treatment led to an increase in TMZ-induced cell apoptosis from 4% to 8%. Importantly, it did not affect the mRNA expression level of Cx43. Concomitant treatment with the translation inhibitor cycloheximide (CHX) exerted additional effects on Cx43 degradation. Treatment with the autophagy inhibitor 3-MA (methyladenine) did not affect the curcumin-induced Cx43 degradation. Interestingly, treatment with the proteasome inhibitor MG132 (carbobenzoxy-Leu-Leu-leucinal) significantly negated the curcumin-induced Cx43 degradation, which suggests that curcumin-induced Cx43 degradation occurs through the ubiquitin-proteasome pathway.

Prior studies suggest that individual differences in stress responses contribute to the pathogenesis of neuropsychiatric disorders. In the present study, we investigated the role of small ubiquitin-like modifier (SUMO) E3 ligase protein inhibitor of activated STAT1 (PIAS1) in mediating stress responses to chronic social defeat stress (CSDS). We found that mRNA and protein levels of PIAS 1 were decreased in the hippocampus of high-susceptibility (HS) mice but not in low-susceptibility (LS) mice after CSDS. Local overexpression of PIAS1 in the hippocampus followed by CSDS exposure promoted stress resilience by attenuating social avoidance and improving anxiety-like behaviors. Viral-mediated gene transfer to generate a conditional knockdown of PIAS1 in the hippocampus promoted social avoidance and stress vulnerability after subthreshold microdefeat. HS mice displayed decreased levels of glucocorticoid receptor (GR) expression, and GR SUMOylation in the hippocampus was associated with stress vulnerability. Furthermore, cytokine/chemokine levels were changed predominantly in the hippocampus of HS mice. These results suggest that hippocampal PIAS1 plays a role in the regulation of stress susceptibility by post-translational modification of GRs.

To evaluate the time efficiency and patient preference of three impression techniques by comparing immediate digital impression performed directly after implantation with regular digital impression and conventional implant impression performed 3 months after implantation.Twenty consecutive patients with a missing single molar or premolar who received implant treatment were recruited into this prospective self-controlled clinical trial. Three different impression techniques were performed after implant surgery on all the participants: An intraoral scanning (IOS) impression performed immediately after implant placement (immediate digital impression) was compared with a regular digital impression and a classic polyether impression (conventional implant impression) performed 3 months after implant surgery. The operating time of each impression technique was recorded. Patients were asked to complete a visual analogue scale (VAS) questionnaire on their perception of the three techniques to describe their satisfaction and preference. Statistical analyses were performed with the Wilcoxon signed rank test.The clinical time of the immediate digital impression (10.97 ± 2.1 min) was significantly shorter than that of the conventional implant impression (14.45 ± 3.0 min) (P0.05). The mean time of the immediate digital impression (10.97 ± 2.1 min) was statistically the same as that of the regular digital impression (10.23 ± 2.7 min) (P0.05). Participants' subjective evaluation indicated higher satisfaction with the immediate digital impression than with the regular digital impression and the conventional implant impression.The immediate digital impression was more efficient than the conventional implant impression and had the same efficiency as the regular digital impression. Among the three impression techniques, the participants showed higher satisfaction with the immediate digital impression.

Stressful events promote psychopathogenic changes that might contribute to the development of mental illnesses. Some individuals tend to recover from the stress response, while some do not. However, the molecular mechanisms of stress resilience during stress are not well-characterized. Here, we identify proteomic changes in the hippocampus using proteomic technique to examine mice following chronic social defeat stress. We showed that small ubiquitin-like modifier (SUMO)-1 expression was significantly decreased in susceptible mice following chronic social defeat stress. We also examined a protein inhibitor of activated signal transducer of transcription (PIAS)1 levels, an E3 SUMO-protein ligase protein inhibitor of activated STAT1, which is known to interact with SUMO-1. PIAS1 was shown to be profoundly decreased and monoamine oxidase (MAO)-A increased in the hippocampus of susceptible mice following chronic social defeat stress. Furthermore, the manipulated PIAS1 expression in the hippocampus also has an influence on glucocorticoid receptor (GR) translocation. We also found that knockdown of PIAS1 expression in the hippocampus then subject to submaximal stress increased GR to glucocorticoid response element (GRE)-binding site on the MAO-A promoter. The present study raises the possibility of different levels of PIAS1 between individuals in response to chronic social defeat stress and that such differences may contribute to the susceptibility to stress.

Increasing studies suggest that inflammatory processes in the central nervous system mediated by microglial activation plays an important role in numerous neurodegenerative diseases. Development of planning for microglial suppression is considered a key strategy in the search for neuroprotection. Paeonol is a major phenolic component of Moutan Cortex, widely used as a nutrient supplement in Chinese medicine. In this study, we investigated the effects of paeonol on microglial cells stimulated by inflammagens. Paeonol significantly inhibited the release of nitric oxide (NO) and the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Treatment with paeonol also reduced reactive oxygen species (ROS) production and inhibited an ATP-induced increased cell migratory activity. Furthermore, the inhibitory effects of neuroinflammation by paeonol were found to be regulated by phosphorylated adenosine monophosphate-activated protein kinase-α (AMPK-α) and glycogen synthase kinase 3 α/β (GSK 3α/β). Treatment with AMPK or GSK3 inhibitors reverse the inhibitory effect of neuroinflammation by paeonol in microglial cells. Furthermore, paeonol treatment also showed significant improvement in the rotarod performance and microglial activation in the mouse model as well. The present study is the first to report a novel inhibitory role of paeonol on neuroinflammation, and presents a new candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.

The ternary system of K2SO4 + KCl + H2O at 303.15 K was studied by the method of isothermal solution saturation and wet residues. The solubility and density of the system were determined and the equilibrium solids were also investigated by the Schreinemaker’s method and verified by X-ray diffraction. On the basis of the experimental data, the phase diagram and the diagram of density versus composition were plotted. The ternary system had two uninvariant curves, one cosaturated point (K2SO4 + KCl), and two crystalline regions corresponding to K2SO4 and KCl. The crystallization region of K2SO4 was much larger than that of KCl. The system was a simple eutectic type, in which neither double salt nor solid solution was formed. The research can offer meaningful data support for industry and a forthcoming study. These data could be conducive to the processes of separation and crystallization in the chemical industry.

Inhibition of microglial over-activation is an important strategy to counter balance neurodegenerative progression. We previously demonstrated that the adenosine monophosphate-activated protein kinase (AMPK) may be a therapeutic target in mediating anti-neuroinflammatory responses in microglia. Brain-derived neurotrophic factor (BDNF) is one of the major neurotrophic factors produced by astrocytes to maintain the development and survival of neurons in the brain, and have recently been shown to modulate homeostasis of neuroinflammation. Therefore, the present study focused on BDNF-mediated neuroinflammatory responses and may provide an endogenous regulation of neuroinflammation. Among the tested neuroinflammation, epigallocatechin gallate (EGCG) and minocycline exerted BDNF upregulation to inhibit COX-2 and proinflammatory mediator expressions. Furthermore, both EGCG and minocycline upregulated BDNF expression in microglia through AMPK signaling. In addition, minocycline and EGCG also increased expressions of erythropoietin (EPO) and sonic hedgehog (Shh). In the endogenous modulation of neuroinflammation, astrocyte-conditioned medium (AgCM) also decreased the expression of COX-2 and upregulated BDNF expression in microglia. The anti-inflammatory effects of BDNF were mediated through EPO/Shh in microglia. Our results indicated that the BDNF-EPO-Shh novel-signaling pathway underlies the regulation of inflammatory responses and may be regarded as a potential therapeutic target in neurodegenerative diseases. This study also reveals a better understanding of an endogenous crosstalk between astrocytes and microglia to regulate anti-inflammatory actions, which could provide a novel strategy for the treatment of neuroinflammation and neurodegenerative diseases.

In order to get an image with every object in focus, an image fusion process is required to fuse the images under different focal settings. In this paper, a novel multifocus image fusion algorithm based on multiresolution transform and particle swarm optimization (PSO) is proposed. Firstly the source images are decomposed into lowpass subbands coefficients and highpass subbands coefficients by the nonsubsampled contourlet transform (NSCT). Then, different fusion rules are applied for low and high frequency NSCT coefficients. Finally the fused image is reconstructed by the inverse NSCT transform. The experiment results demonstrate that the proposed method is effective and can provide better performance than the method based on the wavelet transform and the nonsubsampled contourlet transform.

In order to get an image with every object in focus, an image fusion process is required to fuse the images under different focal settings. In this paper, a new multifocus image fusion algorithm is proposed. The algorithm is based on Laplacian pyramid and Gabor filters. The source images are decomposed by Laplacian pyramid, then the directional edges feature and detail information can be obtained by Gabor filters. Different fusion rules are applied to the low frequency and high frequency coefficients. The experimental results show that the algorithm is simple and effective.

Accumulating evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play important roles in several neurodegenerative disorders. Therefore, development of methods for microglial inhibition is considered an important strategy in the search for neuroprotective agents. Caffeic acid phenethyl ester (CAPE) is distributed wildly in nature, but rapid decomposition by esterase leads to its low bioavailability. In this study, we investigated the effects of KS370G, a novel caffeic acid phenylethyl amide, on microglial activation. KS370G significantly inhibited the release of nitric oxide (NO) and the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Treatment with KS370G also induced heme oxygenase (HO)-1 and suppressors of cytokine signaling (SOCS)-3 expression in the microglia. Furthermore, the anti-inflammatory effects of KS370G were found to be regulated by phosphorylated adenosine monophosphate-activated protein kinase-α (AMPK-α) translocated to the nucleus. Moreover, KS370G showed significant anti-neuroinflammatory effects on microglial activation in vivo and on motor behavior as well. The protective effect of KS370G was weakened by an AMPK inhibitor Compound C. This study focuses on the importance of key molecular determinants of inflammatory homeostasis, AMPK, HO-1, and SOCS-3, and their possible involvement in anti-neuroinflammatory responses.

This paper investigates behaviors of the anchorage connections for buckling restrained braces (BRBs). Finite element (FE) models are established by using software ABAQUS to simulate some tests reported in Part 1 of the companion papers. The material nonlinearities of concrete, anchor bars and anchor plates with the contact property between them are considered in the FE models. A numerical formula is developed for predicting the shear stiffness of anchor bars based on the results from the parametric study using ABAQUS. A formula dealing with the tensile stiffness of the anchor bars is presented relied on the theoretical study. Both of the proposed formulas are verified with the test results. Some design suggestions of the anchorage connections for buckling restrained braces are presented on the basis of the theoretical and experimental studies.

Ultrasound images are the important foundation for disease diagnostics. Unfortunately, speckle noise is an inherent property of ultrasound images. So speckle reduction is an important pre-processing step in the ultrasound image feature extraction and analysis. This paper proposes a novel noise reduction algorithm for ultrasound images, which is based on edge detection of the images using the directional information of contourlet transform. The relative variance of the contourlet coefficients is used as a measure of edge detection. The adaptive threshold can be calculated using the probability density function of relative variance. It is shown that the proposed method outperforms several existing techniques in terms of the universal index, edge preservation and visual quality, and in addition, is able to maintain the significant details of ultrasound images.

Purpose To evaluate the efficacy of sequential posterior subtenon triamcinolone acetonide (PSTA) injection with macular grid/focal laser photocoagulation for clinically significant diabetic macular edema (CSME). Methods Prospective, interventional clinical trial. Between July 2007 and March 2008, 41 eyes of 32 patients (17 males and 15 females) with Type II diabetes mellitus and diffuse clinically significant macular edema according to the Early Treatment Diabetic Retinopathy Study criteria were recruited. PSTA was used as the first line of treatment, followed by macular focal/grid photocoagulation 2 weeks later. In patients with persistent macular edema, a second dose of PSTA followed by additional focal laser treatment was administered 8–10 weeks later. Results Best-corrected visual acuity (BCVA) calculated as logarithm of the minimum angle of resolution (logMAR) unit showed significant improvement both after 3 weeks (0.79 ± 0.27, p = 0.001) and after 6 months (0.77 ± 0.29, p = 0.001) in comparison with the baseline values 0.92 ± 0.24. Central macular thickness (CMT) was significantly reduced both after 3 weeks (336.2 ± 125.8 μm, p = 0.001) and after 6 months (342.2 ± 127.2 μm, p = 0.001) in comparison with the baseline values 437.1 ± 186.5 μm. Total macular volume (TMV) was also significantly reduced both after 3 weeks (10.2 ± 1.8 mm3, p Conclusion One or two sessions of sequential PSTA injection and macular grid/focal photocoagulation may improve or stabilize visual acuity, CMT, and TMV for at least 6 months in patients with CSME.

PurposeThis study was conducted to determine the incidence, risk factors, and treatment for retinopathy of prematurity (ROP) among very low birth weight (VLBW) infants.MethodsThis work is a retrospective, observational analysis of all VLBW infants managed at National Taiwan University Hospital from 2002 to 2005.ResultsThe chart data of 96 VLBW infants were reviewed. Seven of the 96 infants (7.3%) were noted to have no ROP, while 18 infants (18.7%) had minor ROP (stage 1 and stage 2 ROP) and 71 infants (74%) had severe ROP (greater than stage 2 ROP). With lower gestational age, lower birth body weight, greater degree of respiratory distress syndrome, prolonged use of oxygen, and without maternal history of antenatal steroid use, the incidence of severe ROP (greater than stage 2) increased significantly (p

Harbin lies in high altitude region where residential insolation has always been a sensitive and important problem in planning and construction of residential areas. As the high-rise high-density development mode plays a leading role in metropolitan residential area construction, the sunshine issues and contradiction have been highlighted. This paper aims to conduct an in-depth study on sunshine environment on Dahan Day by choosing Harbin representative high-rise residential districts. It dissects this problem in detail from three perspectives respectively, outdoor venue shadow, indoor sunshine occlusion and typical residential sunshine duration of high-rise dwelling compared with multi-storey residence, which contributes to exposing the severe current situation and diagnosing the root causes of high-rise sunshine occlusion phenomenon. Based on the new sunlight standard, suggestions are put forward in introspection on improvement of related auxiliary mechanism, multi-party balance of interest, and supervision of new standard implementation.

The changing law of internal forces during the whole deformation development process was analyzed. The process was divided into five stages based on the internal force state of the beam and the assumptions of internal force relationship of five stages were proposed. Then, the formulas for determining the midspan deflection of the steel beam under distributed load, which was restrained both in rotational and axial directions, were obtained using restraint coefficient method and rigid-plastic mechanism, thereby the deformation development process was expressed accurately in a quantified way. Priority was given to the analysis of the process from bending to tension-bending, then the final state totally depends on tension to resist the external loads, that is the problem of catenary action of the restrained beam under distributed load. Additionally, finite element analysis was carried out with software ABAQUS6.7 on a restrained steel beam under distributed load with different axial and rotational restraint coefficients. The accuracy of the formulas presented was verified by the results of the behavior of the restrained beams. Finally, error analysis was conducted and some formulas were corrected according to the reasons of errors. The calculated results of corrected formulas match the FEM analysis results better, thus the accuracy of these formulas is improved.

The opportunistic fungus Candida albicans causes oral thrush and vaginal candidiasis, as well as candidaemia in immunocompromised patients including those undergoing cancer chemotherapy, organ transplant and those with AIDS. We previously found that the AMPs (antimicrobial peptides) LL37 and hBD-3 (human β-defensin-3) inhibited C. albicans viability and its adhesion to plastic. For the present study, the mechanism by which LL37 and hBD-3 reduced C. albicans adhesion was investigated. After AMP treatment, C. albicans adhesion to plastic was reduced by up to ~60% and was dose-dependent. Our previous study indicated that LL37 might interact with the cell-wall β-1,3-exoglucanase Xog1p, which is involved in cell-wall β-glucan metabolism, and consequently the binding of LL37 or hBD-3 to Xog1p might cause the decrease in adhesion. For the present study, Xog1p(41–438)-6H, an N-terminally truncated, active, recombinant construct of Xog1p and Xog1p fragments were produced and used in pull-down assays and ELISA in vitro , which demonstrated that all constructs interacted with both AMPs. Enzymatic analyses showed that LL37 and hBD-3 enhanced the β-1,3-exoglucanase activity of Xog1p(41–438)-6H approximately 2-fold. Therefore elevated Xog1p activity might compromise cell-wall integrity and decrease C. albicans adhesion. To test this hypothesis, C. albicans was treated with 1.3 μM Xog1p(41–438)-6H and C. albicans adhesion to plastic decreased 47.7%. Taken together, the evidence suggests that Xog1p is one of the LL37/hBD-3 targets, and elevated β-1,3-exoglucanase activity reduces C. albicans adhesion to plastic.

To explore a method of constructing universal 3-dimensional (3D) colorized digital dental model which can be displayed and edited in common 3D software (such as Geomagic series), in order to improve the visual effect of digital dental model in 3D software.The morphological data of teeth and gingivae were obtained by intra-oral scanning system (3Shape TRIOS), constructing 3D digital dental models. The 3D digital dental models were exported as STL files. Meanwhile, referring to the accredited photography guide of American Academy of Cosmetic Dentistry (AACD), five selected digital photographs of patients'teeth and gingivae were taken by digital single lens reflex camera (DSLR) with the same exposure parameters (except occlusal views) to capture the color data. In Geomagic Studio 2013, after STL file of 3D digital dental model being imported, digital photographs were projected on 3D digital dental model with corresponding position and angle. The junctions of different photos were carefully trimmed to get continuous and natural color transitions. Then the 3D colorized digital dental model was constructed, which was exported as OBJ file or WRP file which was a special file for software of Geomagic series. For the purpose of evaluating the visual effect of the 3D colorized digital model, a rating scale on color simulation effect in views of patients'evaluation was used. Sixteen patients were recruited and their scores on colored and non-colored digital dental models were recorded. The data were analyzed using McNemar-Bowker test in SPSS 20.Universal 3D colorized digital dental model with better color simulation was constructed based on intra-oral scanning and digital photography. For clinical application, the 3D colorized digital dental models, combined with 3D face images, were introduced into 3D smile design of aesthetic rehabilitation, which could improve the patients' cognition for the esthetic digital design and virtual prosthetic effect.Universal 3D colorized digital dental model with better color simulation can be constructed assisted by 3D dental scanning system and digital photography. In clinical practice, the communication between dentist and patients could be improved assisted by the better visual perception since the colorized 3D digital dental models with better color simulation effect.

Microglial activation has been widely demonstrated to mediate inflammatory processes that are crucial in several neurodegenerative disorders. Pharmaceuticals that can deliver direct inhibitory effects on microglia are therefore considered as a potential strategy to counter balance neurodegenerative progression. Caffeic acid phenethyl ester (CAPE), a natural phenol in honeybee propolis, is known to possess antioxidant, anti-inflammatory and anti-microbial properties. Accordingly, the current study intended to probe the effects of CAPE on microglia activation by using in vitro and in vivo models. Western blot and Griess reaction assay revealed CAPE significantly inhibited the expressions of inducible nitric oxide synthase (NOS), cyclooxygenase (COX)-2 and the production of nitric oxide (NO). Administration of CAPE resulted in increased expressions of hemeoxygenase (HO)-1and erythropoietin (EPO) in microglia. The phosphorylated adenosine monophosphate-activated protein kinase (AMPK)-α was further found to regulate the anti-inflammatory effects of caffeic acid. In vivo results from immunohistochemistry along with rotarod test also revealed the anti-neuroinflammatory effects of CAPE in microglia activation. The current study has evidenced several possible molecular determinants, AMPKα, EPO, and HO-1, in mediating anti-neuroinflammatory responses in microglial cells.

Glioblastoma multiforme (GBM) is the most common type of primary and malignant tumor occurring in the adult central nervous system. Temozolomide (TMZ) has been considered to be one of the most effective chemotherapeutic agents to prolong the survival of patients with glioblastoma. Many glioma cells develop drug-resistance against TMZ that is mediated by increasing O-6-methylguanine-DNA methyltransferase (MGMT) levels. The expression of connexin 43 was increased in the resistant U251 subline compared with the parental U251 cells. The expression of epithelial–mesenchymal transition (EMT)-associated regulators, including vimentin, N-cadherin, and β-catenin, was reduced in the resistant U251 subline. In addition, the resistant U251 subline exhibited decreased cell migratory activity and monocyte adhesion ability compared to the parental U251 cells. Furthermore, the resistant U251 subline also expressed lower levels of vascular cell adhesion molecule (VCAM)-1 after treatment with recombinant tumor necrosis factor (TNF)-α. These findings suggest differential characteristics in the drug-resistant GBM from the parental glioma cells.

Accumulating evidence suggests that neuroinflammation is closely associated with the pathogenesis of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. The hallmark of neuroinflammation is considered to be microglial activation in the central nervous system (CNS). Activated microglia release pro-inflammatory cytokines which cause neuroinflammation and progressive neuronal cell death. Therefore, inhibition of microglial activation is considered an important strategy in the development of neuroprotective strategy. Naringenin, a flavonoid found in citrus fruits and tomatoes, has been reported to have anti-oxidant, anti-cancer, and anti-inflammatory properties. However, the mechanism of its beneficial anti-inflammatory effects in the CNS is poorly understood. In this study, we demonstrated that naringenin inhibites the release of nitric oxide (NO), the expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), as well as pro-inflammatory cytokines in microglial cells. Treatment of naringenin also induced suppressors of cytokine signaling (SOCS)-3 expression in microglia. The SOCS-3 expression and anti-inflammatory effects of naringenin were found to be regulated by adenosine monophosphate-activated protein kinase α (AMPKα) and protein kinase C δ (PKCδ). Besides, naringenin exerted protective property against neurotoxicity caused by LPS-induced microglial activation. Our findings suggest that naringenin-inhibited iNOS and COX-2 expression is mediated by SOCS-3 activation through AMPKα and PKCδ signaling pathways. In a mouse model, naringenin also showed significant protective effects on microglial activation and improved motor coordination function as well. Therefore, naringenin that involves in anti-neuroinflammatory responses and neuroprotection might be a potential agent for treatment of inflammation-associated disorders.

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Background Eosinophil cationic protein is a clinical asthma biomarker that would be released into blood, especially gathered in bronchia. The signal peptide of eosinophil cationic protein (ECPsp) plays an important role in translocating ECP to the extracellular space. We previously reported that ECPsp inhibits microbial growth and regulates the expression of mammalian genes encoding tumor growth factor-α (TGF-α) and epidermal growth factor receptor (EGFR). Results In the present study, we first generated a DNA microarray dataset, which showed that ECPsp upregulated proinflammatory molecules, including chemokines, interferon-induced molecules, and Toll-like receptors. The levels of mRNAs encoding CCL5, CXCL10, CXCL11, CXCL16, STAT1, and STAT2 were increased in the presence of ECPsp by 2.07-, 4.21-, 7.52-, 2.6-, 3.58-, and 1.67-fold, respectively. We then constructed a functional linkage network by integrating the microarray dataset with the pathway database of Kyoto Encyclopedia of Genes and Genomes (KEGG). Follow-up analysis revealed that STAT1 and STAT2, important transcriptional factors that regulate cytokine expression and release, served as hubs to connect the pathways of cytokine stimulation (TGF-α and EGFR pathways) and inflammatory responses. Furthermore, integrating TGF-α and EGFR with the functional linkage network indicated that STAT1 and STAT2 served as hubs that connect two functional clusters, including (1) cell proliferation and survival, and (2) inflammation. Finally, we found that conditioned medium in which cells that express ECPsp had been cultured could chemoattract macrophages. Experimentally, we also demonstrated that the migration of macrophage could be inhibited by the individual treatment of siRNAs of STAT1 or STAT2. Therefore, we hypothesize that ECPsp may function as a regulator for enhancing the migration of macrophages through the upregualtion of the transcriptional factors STAT1 and STAT2. Conclusion The increased expression and release of various cytokines triggered by ECPsp may attract macrophages to bronchia to purge damaged cells. Our approach, involving experimental and computational systems biology, predicts pathways and potential biological functions for further characterization of this novel function of ECPsp under inflammatory conditions.

The signal peptide of eosinophil cationic protein (ECPsp) is known to play an important role in translocating ECP to extracellular space. However, we previously discovered that ECPsp has a novel function of inhibiting microbial growth and regulating the gene expression of tumor growth factor-alpha (TGF-α) and epidermal growth factor receptor (EGFR) in mammalian cells. In the present study, we first generated a DNA microarray dataset, which showed that ECPsp up-regulated inflammatory molecules including cytokines, chemokines, interferon-induced molecules, and Toll-like receptors. We then generated a function linkage network by integrating the microarray dataset with the KEGG pathway database, and discovered that STAT1, an important factor regulating cytokine expression and release, served as a hub to connect the pathways of cytokine stimulation (TGF-α and EGFR) and inflammatory responses. Furthermore, integrating the ECPsp interactome dataset with the functional linkage network elucidated that STAT1 served as a hub to connect 3 functional clusters, including cell proliferation and survival, protein translational regulation, and inflammatory responses. Our approach involving experimental and computational systems biology provided predicted pathways and potential regulation for further characterization of the novel function of ECPsp under inflammatory conditions.

A target tracking algorithm based on particle swarm optimization (PSO) is proposed. Due to a premature convergence with PSO in multimodal problems, an improved PSO, i.e. hierarchic particle swarm optimization (HPSO), is proposed and utilized to track target. To maintain high diversity of particle swarm, dynamic propagation is utilized to generate new particles in tracking process. In addition, parameters in PSO are adaptively adjustment in iteration process, leading to a favorable performance in tracking applications. Experiment results demonstrate the proposed algorithm is accurate and effective.

Diverse pose estimation of three-dimensional (3D) object in the whole view-space remains a challenge in the field of pattern recognition. In this paper, a pose estimation algorithm of 3D object named isomap-eigenanalysis-regression (Isomap-E-R), which estimates arbitrary pose of 3D object in the whole view space, is proposed. For the training set, the low-dimensional embedding of input pattern set is computed by isomap, and the eigen-images of the embedding are deduced on the basis of an eigenspace. A different projection direction in low dimensional embedding is utilized to improve the accuracy of pose estimation. The metrics on each direction, derived by linear regression, is then used to further deduce the projection of the training set. For a given new sample, its projection onto the eigen-images is first computed, and the training images nearest to those deduced for the new sample by the algorithm give the estimation poses. The performance analysis on the obtained experimental results demonstrated that the proposed method could estimate the diverse pose of 3D object with significant efficiency and precision. Finally, the algorithm can be also extended to real-time pose estimate of 3D object and other potential applications.

A method is presented to obtain maps between the high-dimensional data and the low-dimensional space deduced by locally linear embedding (LLE). Since LLE does not provide a parametric function that build maps between the image space and the low-dimensional manifold. In this paper, multivariate linear regression is applied to deduce the maps. It can successfully project a new data point onto the embedded space. Also it can be extended to supervised LLE. The performance analysis on the obtained experimental results demonstrated that the proposed method is effective and efficient.

In traditional spectral clustering algorithms, the number of cluster is choosen in advance. A self-adaption spectral clustering algorithm is proposed to decide the cluster number automatically, which eliminates the drawbacks of two kinds of spectral clustering methods. In our algorithm, eigengap is used to discover the clustering stability and decide the cluster number automatically. We prove theoretically the rationality of cluster number using matrix perturbation theory. A kernel based fuzzy c-means is introduced to spectral clustering algorithm to separate clusters. Finally the experiments prove that our algorithm tested in the UCI data sets may get better results than c-means, Ng et.al's algorithm and Francesco et.al's algorithm.