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Circular RNAs (circRNAs), is a novel type of endogenous non-coding RNAs (ncRNAs) participated in the pathogenesis of many diseases. Beryllium is one of the carcinogenesis elements. However, the mechanism and function of circRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4) was rarely reported. Therefore, the high-throughput RNA sequencing analysis was performed to detect the circRNA profiles between control groups and BeSO4-induced groups. Furthermore, circRNA-miRNA-mRNA network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and PPI network analysis were used for bioinformatics analysis. CircRNA sequencing analysis revealed that 36 circRNAs were up-regulated and 35 circRNAs were down-regulated in the BeSO4-exposed groups. The selected circRNAs were verified by real-time fluorescent quantitative PCR (qRT-PCR). Hsa_circ_0004214 and hsa_circ_0003586 were validated to be up-regulated, hsa_circ_0047958, hsa_circ_0001944, and hsa_circ_0008982 were down-regulated. The circRNA-miRNA-mRNA network annotated the key signaling pathway including cellular senescence, TNF signaling pathway, NF-kappa B signaling pathway, HIF-1 signaling pathway, and Hippo signaling pathway. The PPI network indicated the most circRNAs might participate in the BeSO4 toxicity by acting as a sponge for the miR-663b through JAK–STAT signaling pathway. In summary, our study suggests that circRNAs may play roles in the mechanism of beryllium toxicity.

Some industrial wastewater containing complicated contents (e.g., heavy metals and organics) and extensive concentration-variation cannot be well-treated by physical-chemical treatment processes. In order to obtain the feasible electrochemical technique, an electrocatalytic-membrane process (ECMP) was established to treat such wastewater from a mint factory in Taiwan. Wastewater samples with pollutants of Cu2+, Ni2+ and chemical oxygen demand (COD) were categorized into three types based on pH and concentrations. The complexity of wastewater is attributed that a verity of chemical reagents and manufacturing methods are employed to produce different kind of coins. In this study, each type of wastewater was treated by the ECMP and integrated with other techniques to find out the appropriate procedures. Results indicate that the sole ECMP can effectively remove the Cu2+, Ni2+, and COD when the wastewater is with relatively low pH (around 3–5), low COD (around 50 mg L−1), and high concentration of heavy metals (Cu2+ concentration over 500 mg L−1). However, the ECMP should combine with pH-adjustment to effectively remove the Cu2+, Ni2+, and COD when the wastewater is with very low pH (close to 1), high COD (over 200 mg L−1), and high concentration of heavy metals. In addition, the ECMP has to link the electrocoagulation (ECG) to decrease the Cu2+, Ni2+, and COD concentration when the wastewater is with neutral pH (around 7), middle-level COD (around 130 mg L−1), and low concentration of heavy metals (Cu2+ concentration around 1.0 mg L−1). Accordingly, the ECMP integrated with other treatment processes gains potential to treat refractory wastewater.

The rotavirus (RV) is the most important causative agent of severe gastroenteritis in infants and children aged less than 5 years worldwide. However, the response and the roles of peripheral blood mononuclear cell (PBMC) in RV clearance have yet to be fully elucidated. In this study, we established the neonatal rhesus monkey model of RV infection with histopathological changes in the small intestine. Then, we investigated gene expression changes in PBMCs from the monkey model of RV infection. Similar pathways regulated in rhesus monkeys that received intragastric administration of the RV monkey SA11 strain (G3P[2]) and the human wild-type strain ZTR-68 (G1P[8]). Gene profiling showed differences in functional genes mainly associated with chemokine signaling pathways and cytokine-cytokine receptor interactions post RV infection. Transferrin and C-C motif chemokine ligand 23 (CCL23) gene expression were upregulated in PBMCs of monkeys when stimulated by simian and human RV strains. Monkeys infected with RV had an enhanced and prolonged inflammatory response that was associated with increased levels of CCL20, CCL23, and C-X-C motif chemokine ligand 1; while inhibition of major histocompatibility complex class I expression may be important for immune evasion by RV. The RV infection was also characterized by pathological changes in the small intestine with a cytokine and chemokine storm. This study identified the chemokine signaling pathway and immune response genes involved in RV infection in infant rhesus monkeys. The SA11 RV strain is more suitable for establishing a monkey diarrhea model than the ZTR-68 RV strain.

AIM To determine the distribution of rotavirus VP7 gene in hospitalized children in Yunnan, China. METHODS A total of 366 stool specimens were collected from hospitalized children in hospitals in Yunnan Province from September 2010 to December 2013. The genomic RNA electropherotypes and the G genotypes of the rotaviruses were determined. A phylogenetic analysis of the VP7 gene was performed. Rotavirus isolation was performed, and characterized by plaque, minimum essential medium, and all genes sequence analysis. Quantification of antibodies for inactivated vaccine prepared with ZTR-68 was examined by enzyme-linked immunosorbent assay and microneutralization assay. RESULTS Group A human rotavirus was detected in 177 of 366 (48.4%) stool samples using a colloidal gold device assay. The temporal distribution of rotavirus cases showed significant correlation with the mean air temperature. Rotaviruses were isolated from 13% of the rotavirus-positive samples. The predominant genotype was G1 (43.5%), followed by G3 (21.7%), G9 (17.4%), G2 (4.3%), G4 (8.7%), and mixed (4.3%) among a total of 23 rotavirus isolates. A rotavirus strain was isolated from a rotavirus-positive stool sample of a 4-month-old child in The First People’s Hospital of Zhaotong (2010) for use as a candidate human inactivated rotavirus vaccine strain and for further research, and was designated ZTR-68. The genotype of 11 gene segments of strain ZTR-68 (RVA/Human-wt/CHN/ZTR-68/2010/G1P[8]) was characterized. The genotype constellation of strain ZTR-68 was identified as G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. The VP7 and VP4 genotypes of strain ZTR-68 were similar to Wa-like strains. CONCLUSIONS A high prevalence of the G1, G2, and G3 genotypes was detected from 2010 to 2012. However, a dominant prevalence of the G9 genotype was identified as the cause of gastroenteritis in children in Yunnan, China, in 2013. A candidate human inactivated rotavirus vaccine strain, designated ZTR-68 was isolated, characterized, and showed immunogenicity. Our data will be useful for the future formulation and development of a vaccine in China.

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X21992896 for Effects of mild hypoxia on oxygen extraction fraction responses to brain stimulation by Yayan Yin, Su Shu, Lang Qin, Yi Shan, Jia-Hong Gao and Jie Lu in Journal of Cerebral Blood Flow & Metabolism

Beryllium and its compounds are systemic toxicants that mainly accumulate in the lungs. As a regulator of gene expression, microRNAs (miRNAs) were involved in some lung diseases. This study aimed to analyze the levels of some inflammatory cytokine and the differential expressions of miRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4 ) and to further explore the biological functions of differentially expressed miRNAs. The profile of miRNAs in 16HBE cells was detected using the high-throughput sequencing between the control groups (n = 3) and the 150 μmol/L of BeSO4 -treated groups (n = 3). Bioinformatics analysis of differentially expressed miRNAs was performed, including the prediction of target genes, Gene Ontology (GO) analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify some damage-related miRNAs. We found that BeSO4 can increase the levels of some inflammatory cytokine such as interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). And BeSO4 altered miRNAs expression of 16HBE cells and a total of 179 differentially expressed miRNAs were identified, including 88 upregulated miRNAs and 91 downregulated miRNAs. The target genes predicted by 28 dysregulated miRNAs were mainly involved in the transcription regulation, signal transduction, MAPK, and VEGF signaling pathway. The qRT-PCR verification results were consistent with the sequencing results. miRNA expression profiling in 16HBE cells exposed to BeSO4 provides new insights into the toxicity mechanism of beryllium exposure.

This study aims to clarify the removal mechanism and to calculate the effective current of electrocoagulation (i.e., EC) for treating wastewater containing Ni(II), Cu(II), and Cr(VI). The adsorption behavior of various heavy metals onto Al(OH)3 coagulant generated by the EC process was investigated and the estimating method of the corresponding current was established. Results indicate that adsorption of single Ni(II) and Cu(II) by Al(OH)3 coagulant can be simulated by the Langmuir isotherm, while Cr(VI) adsorption fits the Freundlich isotherm better. As treating single heavy metal of wastewater, the removal mechanism of the EC process is the adsorption reaction. Under the coexisting condition, the Ni(II) and Cu(II) will compete for the same active sites on the Al(OH)3 surface and Cu(II) suppresses Ni(II) adsorption. As treating the coexisting heavy metals, Ni(II) removal not only associates with adsorption but also with the coprecipitation. In contrast, Cr(VI) does not compete with other metal ions for the same type of adsorption sites. Whether single or coexisting conditions, the adsorption capacity of heavy metals onto Al(OH)3 coagulants can be used to compute the necessary current to effectively remove heavy metals in the EC system.

A series of experiments with different NaCl concentrations added to the PCB (printed circuit board) wastewater were prepared to investigate the chloride effect on the formation of aluminum floc and removal efficiency of Cu and Ni. The effects of pH, current density, and different concentration of NaCl were studied and the results are discussed. Results imply that chloride ions are favored to avoid the passivation of the aluminum anode in the EC (electro-coagulation) system. Chloride ions used as the electrolyte can facilitate the release of Al3+, which results in the current efficiency of over 100% in the EC system. For the PCB factory&rsquo, s wastewater, the EC system could remove Cu2+ and Ni2+ effectively (both Cu and Ni concentration of treated wastewater was less than 1.0 mg/L within three minutes). PCB wastewater&rsquo, s pH value could maintain stably about 9.0 in the EC system when the initial pH value was around 2.5. The estimated electricity consumption for treating PCB wastewater by the EC process was about 0.894 kWh for each meter of cubic wastewater.

Rotaviruses are double-stranded RNA viruses that are a major cause of viral diarrhea in infants. Examining virus-host cell interaction is important for elucidating mechanisms of virus proliferation in host cells. Viruses can create an environment that promotes their survival and self-proliferation by encoding miRNAs or miRNA-like molecules that target various host cell. However, it remains unclear whether RNA viruses encode viral miRNAs, and their regulation mechanisms are largely unknown. We previously performed deep sequencing analysis to investigate rotavirus-encoded miRNAs, and identified the small RNA molecule Chr17_1755, which we named RV-vsRNA1755. In our present study, we determined that RV-vsRNA1755 is encoded by the rotavirus NSP4 gene and that it targets the host cell IGF1R, which is part of the PI3K/Akt pathway. We further explored the biological characteristics and functions of RV-vsRNA1755.Our results suggest that rotavirus adapts to manipulate PI3K/Akt signaling at early phases of infection. RV-vsRNA1755 targets IGF1R, blockading the PI3K/Akt pathway and triggering autophagy, but it ultimately inhibits autophagy maturation. A mechanism through which rotavirus encodes a virus-like small RNA (RV-vsRNA1755) that triggers autophagy by targeting the host cell IGF1R gene was revealed. These data provide a theoretical basis for therapeutic drug screening targeting RV-vsRNA1755.

// I-Chun Kuo 1, * , Huang-Kai Kao 2, 3, * , Yenlin Huang 4 , Chun-I Wang 1 , Jui-Shan Yi 1, 5 , Ying Liang 5 , Chun-Ta Liao 1, 3 , Tzu-Chen Yen 3, 6 , Chih-Ching Wu 1, 5, 7 and Kai-Ping Chang 1, 3, 5 1 Department of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan 2 Department of Plastic & Reconstructive Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan 3 College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan 4 Departments of Pathology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan 5 Molecular Medicine Research Center, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan 6 Departments of Nuclear Medicine, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan 7 Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan * These authors have contributed equally to this work Correspondence to: Kai-Ping Chang, email: dr.kpchang@gmail.com Chih-Ching Wu, email: luckywu@mail.cgu.edu.tw Keywords: OSCC, proteome, metastasis, prognosis, ERAP2 Received: September 30, 2016 Accepted: May 23, 2017 Published: June 27, 2017 ABSTRACT Oral cavity squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide and associated with poor prognosis and mortality. Discovery of proteins that can improve OSCC treatment is needed. Using comparative proteome profiling of primary cells derived from OSCC and adjacent noncancerous epithelium, endoplasmic reticulum aminopeptidases 2 (ERAP2) has been identified as an OSCC-associated protein. Compared with the adjacent normal tissues, ERAP2 levels were determined to be significantly elevated in OSCC tissues using quantitative real-time PCR and immunohistochemistry. Importantly, overexpression of ERAP2 was associated with positive N stage, advanced overall stage, positive perineural invasion, and tumor depth ( P = 0.041, 0.015, 0.010, and 0.032, respectively). The overall survival rates of patients without and with the ERAP2 overexpression were 71.9% and 56.0%, respectively ( P = 0.029). Furthermore, knockdown of ERAP2 inhibited the migration and invasion abilities of OSCC cells. Our results collectively show that ERAP2 overexpression is associated with the cervical metastasis and poorer prognosis of OSCC.

Objective Neurotropism of salivary adenoid cystic carcinoma (SACC) and pulmonary metastasis may lead to in treatment failure. miR-582-5p plays important roles in tumorigenesis, invasion and migration. Here, we aim to determine the effect of miR-582-5p and its role in SACC invasion and metastasis. Methods Six primary human SACC samples and matching adjacent normal tissues were analyzed by microarray analysis. Next, quantitative real-time PCR was carried out to evaluate miR-582-5p expression in 16 primary human SACC samples and matching adjacent normal tissues. Cell invasion and migration were also analyzed, and a luciferase reporter assay and western analysis were conducted. Cell growth and apoptosis assay were performed to confirm the effect of miR-582-5p and Forkhead box C1 (FOXC1) siRNA in cell proliferation and apoptosis. SACC tumorigenesis and metastasis were investigated in vivo experiment. Clinical samples from 110 patients were analyzed using in situ hybridization and immunohistochemistry. Results Microarray analysis revealed that miR-582-5p was significantly downregulated in the SACC samples compared with the matching adjacent normal tissues. Regulation of miR-582-5p expression significantly influenced the migration, invasion and proliferation ability of SACC cells by targeting FOXC1. E-cadherin was increased, while vimentin and snail were decreased with downregulation of FOXC1, suggesting that FOXC1 may regulate the epithelial-to-mesenchymal transition (EMT) of SACC cells by transactivating snail. In vivo, miR-582-5p overexpression suppressed the tumorigenesis and pulmonary metastasis of SACC. Lower expression of miR-582-5p expression predicts unfavorable prognoses and high rates of metastasis. Conclusions miR-582-5p could suppress effect on the process of invasion and migration in SACC cell lines, and this could occur through its target gene FOXC1.

Pediatric cheilitis can be a debilitating condition for the child and parents. Patch testing can help isolate allergens to avoid. Here we describe a 2-year-old boy with allergic contact cheilitis improving remarkably after prudent avoidance of contactants and food avoidance.

Epidermal growth factor receptor (EGFR) and activin A are both overexpressed in oral cavity squamous cell carcinoma (OSCC). We evaluated their clinical correlation and activin A-mediated EGFR regulation in this study. Overexpression of both transcripts/proteins indicated a poorer prognosis in OSCC patients. Knockdown of endogenous INHBA repressed the expression of EGFR and inhibited activin A-mediated canonical Smads, noncanonical phosphorylation of AKT (ser473) (p-AKT ser473) and SP1. Inhibition of PI3K signaling via its inhibitor attenuated p-AKT ser473 and in turn reduced SP1 and EGFR expression in the presence of recombinant activin A (rActivin A) in OSCC cells, as revealed via a luciferase assay and western blotting. However, canonical Smad signaling repressed the EGFR promoter, as revealed by a luciferase assay. The transcription factor SP1, its coactivator CBP/p300, and Smad proteins were recruited to the EGFR proximal promoter following rActivin A treatment, as revealed by chromatin immunoprecipitation (ChIP). Smad2/3/4 dramatically outcompeted SP1 binding to the EGFR proximal promoter following mithramycin A treatment. Activin A activates the PI3K and Smad pathways to compete for binding to overlapping SP1 consensus sequences on the EGFR proximal promoter. Nevertheless, canonical p-Smad2 was largely repressed in OSCC tumor tissues, suggesting that the activin A-mediated noncanonical pathway is essential for the carcinogenesis of OSCC.

Background DNA copy number variations (CNVs) are a hallmark of cancer, and the current study aimed to demonstrate the profile of the CNVs for oral cavity squamous cell carcinoma (OSCC) and elucidate the clinicopathological associations and molecular mechanisms of a potential marker derived from CNVs, mixed-lineage leukemia translocated to chromosome 3 protein (MLLT3), in OSCC carcinogenesis. Materials and Methods CNVs in 37 OSCC tissue specimens were analyzed using a high-resolution microarray, the OncoScan array. Gene expression was analyzed by real-time polymerase chain reaction in 127 OSCC and normal tissue samples. Cell function assays included cell cycle, migration, invasion and chromatin immunoprecipitation assays. Results We found a novel copy number amplified region, chromosome 9p, encompassing MLLT3 via the comparison of our data set with six other OSCC genome-wide CNV data sets. MLLT3 overexpression was associated with poorer overall survival in patients with OSCC (p = .048). MLLT3 knockdown reduced cell migration and invasion. The reduced invasion ability in MLLT3-knockdown cells was rescued with double knockdown of MLLT3 and CBP/p300-interacting transactivator with ED rich carboxy-terminal domain 4 (CITED4; 21.0% vs. 61.5%). Knockdown of MLLT3 impaired disruptor of telomeric silencing-1-like (Dot1L)-associated hypermethylation in the promoter of the tumor suppressor, CITED4 (p < .001), and hence dysregulated HIF-1α-mediated genes (TWIST, MMP1, MMP2, VIM, and CDH1) in OSCC cells. Conclusion We identified unique CNVs in tumors of Taiwanese patients with OSCC. Notably, MLLT3 overexpression is related to the poorer prognosis of patients with OSCC and is required for Dot1L-mediated transcriptional repression of CITED4, leading to dysregulation of HIF-1α-mediated genes. Implications for Practice This article reports unique copy number variations in oral cavity squamous cell carcinoma (OSCC) tumors of Taiwanese patients. Notably, MLLT3 overexpression is related to the poorer prognosis of patients with OSCC and is required for Dot1L-mediated transcriptional repression of CITED4, leading to dysregulation of HIF-1α-mediated genes.

Objectives The objectives were to investigate the emergency treatment of serious dog bite lacerations on limbs and to identify whether negative pressure wound therapy (NPWT) was beneficial in these instances. Methods A total of 580 cases with serious limb lacerations due to dog bites were randomly divided into 2 groups. After thorough debridement, the limb lacerations of group A (n = 329) were left open. The remaining cases (n = 251) were randomly divided into 2 subgroups, group B and group C, which were treated with 125 and 75 mm Hg of continuous negative pressure, respectively. Antibiotics were only used in cases where there were systemic signs of wound infection, and were not given prophylactically. The infection rate, infection time, and healing time were analyzed. Results The wound infection rates of groups A, B, and C were 9.1%, 4.1%, and 3.9%, respectively. The infection times of the 3 groups were 26.3 ± 11.6, 159.8 ± 13.4, and 166.4 ± 16.2 hours, respectively. The recovery times of the infection patients in the 3 groups were 19.2 ± 4.6, 13.2 ± 2.1, and 12.7 ± 2.3 days, respectively, and in the noninfection patients, the recovery times were 15.6 ± 2.7, 10.1 ± 2.3, and 10.5 ± 1.9 days, respectively. In groups B (− 125 mm Hg) and C (− 75 mm Hg), the infection rate, infection time, and healing time showed no significant differences. Conclusion Patients with serious dog bite laceration on limbs could benefit from NPWT. Compared with the traditional treatment of leaving the wounds open, NPWT reduced the infection rate and shortened recovery time. When NPWT was performed, low negative pressure (− 75 mm Hg) had the same positive effects as high pressure (− 125 mm Hg). Prophylactic antibiotics administration is not recommended for treating this kind of laceration. Level of evidence Therapeutic/care management, level II.

Rotavirus infection is an important cause of acute gastroenteritis in children, but the interaction between rotavirus and host cells is not completely understood. We isolated a wildtype (wt) rotavirus strain, ZTR-68(P [8] G1), which is derived from an infant with diarrhea in southwest China in 2010. In this study, we investigated host cellular miRNA expression profiles changes in response to ZTR-68 in early stage of infection to investigate the role of miRNAs upon rotavirus infection. Differentially expressed miRNAs were identified by deep sequencing and qRT-PCR and the function of their targets predicted by Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. A total of 36 candidate miRNAs were identified. Comparative analysis indicated that 29 miRNAs were significantly down-regulated and 7 were up-regulated after infection. The data were provided contrasting the types of microRNAs in two different permissive cell lines (HT29 and MA104). The target assays results showed that mml-miR-7 and mml-miR-125a are involved in anti-rotavirus and virus-host interaction in host cells. These results offer clues for identifying potential candidates in vector-based antiviral strategies. J. Med. Virol. 88:1497-1510, 2016. © 2016 Wiley Periodicals, Inc.

BACKGROUND The purpose of this study was to elucidate the clinicopathological associations and molecular mechanisms of karyopherin alpha 2 (KPNA2) in oral cavity squamous cell carcinoma (SCC) progression. METHODS The KPNA2 expressions were analyzed by immunohistochemistry and enzyme-linked immunosorbent assay in 209 tissues and 181 saliva samples, respectively. The functions of KPNA2 in migration and invasion were examined in KPNA2-knowdown cells. The matrix metalloproteinase (MMP) levels were determined by real-time quantitative polymerase chain reaction (qPCR). The subcellular fraction was used to obtain the nuclear distribution of nuclear factor-kappa B (NF-κB). RESULTS The KPNA2 overexpression was associated with extranodal extension (P < .05) and poor disease-specific survival in patients with oral cavity SCC (P < .05). The salivary KPNA2 levels were elevated in patients with oral cavity SCC (P < .05). The KPNA2 knockdown reduced cell migration and invasion. This knockdown also suppressed the interleukin (IL)-1β-induced nuclear import of NF-κB and MMP (MMP-1, MMP-3, and MMP-9) transcription. CONCLUSION The KPNA2 overexpression is an independent biomarker for poor prognosis of oral cavity SCC and is required for MMP-mediated metastasis.

This report compares the efficacy of timolol maleate 0.5% eyedrops (TM) with that of timolol maleate 0.5% ophthalmic gel-forming solution in the treatment of infantile hemangiomas (IHs). Sixty-six patients undergoing treatment with topical timolol were retrospectively reviewed; our results revealed similar therapeutic efficacies for both types of timolol formulations. Early treatment initiation (

The strategies for developing rotavirus (RV) vaccines have always been controversial. At present, both the monovalent RV vaccine and the multivalent RV vaccine have displayed excellent safety and efficacy against RV infection and shown cross-reactive immunity, which laid the question whether the multivalent RV vaccine could be replaced by the monovalent RV vaccine. In this study, we focused on comparing the immunogenicity (serum neutralization activity and protection against homotypic and heterotypic RVs’ challenge) of individual standard RV strains (monovalent RV immunogens) and different combinations of them (multivalent RV immunogens). In result, RV immunogens showed general immunogenicity and heterotypic reaction but the multivalent RV immunogens exhibited greater serum neutralization activity and stronger heterotypic reaction than the monovalent RV immunogens (P

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor; it is highly aggressive and is associated with a poor prognosis. Binding of the chemokine CXCL12 to its receptors (CXCR4 and CXCR7) contributes to the activation of many downstream signaling pathways and promotes the invasion of various malignant tumor cells, including GBM cells. FOXM1, a transcription factor involved in cell cycle regulation, is overexpressed in GBM and is involved in GBM progression. However, the molecular mechanisms by which CXCL12 promotes the invasion of human GBM cells remain unclear. In this study, we demonstrate that CXCL12 increases the production of FOXM1 by binding to CXCR4 in GBM cell lines. Furthermore, pretreatment with an inhibitor of the PI3K/AKT pathway abrogated the CXCL12-induced expression of FOXM1. In addition, there was a positive correlation between CXCL12/CXCR4 expression and FOXM1 expression in human malignant glioma tissues. Finally, a functional assay revealed that CXCL12 does not stimulate GBM cell invasion when FOXM1 expression is silenced using a small interfering RNA (siRNA). Collectively, these findings suggest that CXCL12 promotes GBM cell invasion in part by increasing the expression of FOXM1, which is mediated in part by a PI3K/AKT-dependent mechanism in vitro.

The significant yield of dissolved oxygen (DO) is one advanced advantage of the electrocatalytic technique for wastewater treatment. Here, we measure DO concentrations during electrocatalytic processing of Taiwanese municipal wastewater and landfill leachate. Chloride ion–containing electrolytes in the wastewater had the most deleterious effect on the production of DO. In contrast, other anions including carbonates, nitrates, sulfates, and phosphates improved DO yield. The Cl− effect can account for electrode erosion, because the anode surface will be impacted by chloride ions. This erosion results in the release of metal ions at the anode that react with DO to form species of metal oxides and deplete the DO in wastewater. However, other cations in the wastewater such as Na+, Ca2+, and Mg2+ are irrelevant with the DO yield in the electrocatalytic system. Results indicate that inert anodes such as dimensionally stable anodes can increase DO concentration, but the metal-related anodes such as stain...

Laparoscopy is widely used during living kidney donation, nephrectomy, bariatric surgery, and surgery for gastrointestinal tumors and colorectal cancer. However, laparoscopic surgery requires prolonged use of instruments and has low mechanical efficiency. In addition, to meet specific surgical demands while visualizing the surgical area on the screen, surgical personnel frequently violate the postures proposed by human factor engineering; this naturally results in a physical burden on the personnel. In this study, using laparoscopic nephrectomy as an example, an auxiliary hoisting device for surgery was designed, and pedals from a variety of equipment were integrated into the auxiliary plant. Both entity testing conducted in the hospital and 3D surgical simulation of the auxiliary plant showed that this device could improve compliance with human factor engineering recommendations during laparoscopic surgery and could also promote interaction and tacit understanding between surgical personnel, thereby providing ergonomically optimum conditions during laparoscopy.

Framed curing mold is subjected to an uneven thermal load, gravity force and the pressures from composite parts and auxiliary tools during autoclave processing of thermosetting composite structures. And those loads induce the warpage of framed-mold. The warpage of framed-mold during autoclave processing influences dimensional precision of composite parts. In the present work, a three-dimensional finite element model for prediction of the warpage of framed-mold during autoclave processing has been developed. This model solved the coupling problem between the deformation and the temperature distribution of framed-mold and allows analysis of all major identified deformation influencing factors. And numerical predictions compare quite well with experimental measurements. A parametric study was performed using FEM program to examine the effect of varying the thickness of framed-mold, the shape and the dimension of mold vents.

Apoptosis is a known regulator of morphogenetic events. In mammals, the critical role of oxidative stress-induced apoptosis has been well-studied; however, in insects the role of oxidative stress in apoptosis is not clear. In a previous study, we showed that apoptosis-related genes are present in the silkworm Bombyx mori, an important lepidopteran insect model. In this study, we evaluated the effect of H2O2-induced oxidative stress on apoptosis, reactive oxygen species (ROS) levels, mitochondrial response, cytochrome c release and apoptosis-related gene expression in the BmN-SWU1 cell line from B. mori ovaries. Our results showed that BmN-SWU1 cells exposed to H2O2 showed cell protuberances, cytoplasmic condensation, apoptotic bodies, DNA ladder formation and caspase activities indicating apoptosis. H2O2-induced apoptosis also increased intracellular ROS level, changed mitochondrial distribution, reduced mitochondrial membrane potential and increased the release of cytochrome c from mitochondria. Furthermore, western blot analysis revealed a significant increase in p53 and cytochrome c expression, and a decrease in Bcl-2 expression compared to the controls. Moreover, quantitative real-time PCR (qRT-PCR) showed an increase in the transcript levels of BmICE, Bmapaf-1 and BmEndoG by 439.5%, 423.9% and 42.2%, respectively, after treatment with 1 μM H2O2 for 24 h. However, the transcript levels of Bmbuffy declined by 41.4% after 24 h of exposure to 1 μM H2O2. These results show that H2O2 treatment induced apoptosis in BmN-SWU1 cells via the mitochondrial apoptotic pathway. Further, it appears that oxidative stress induced by H2O2 activates both caspase-dependent and caspase-independent mitochondrial apoptotic pathways in silkworm cells. Taken together, these findings improve our knowledge of apoptosis in silkworm and the apoptotic pathways in insects.

The early inflammatory lesions of morphea may present with erythema or violaceous patches and plaques before evolving into areas of sclerosis. They have been misdiagnosed as acquired port-wine stains (PWSs). We report a previously well 7-year-old Chinese girl presenting with early facial morphea mimicking an acquired PWS with unusual histologic features of perineural inflammation. The presence of cutaneous perineural inflammation may be seen in a small percentage of cases of morphea and appears to be a feature of early inflammatory morphea. We report this case to highlight the importance in recognizing this entity and summarize the reported cases of inflammatory morphea mimicking acquired PWSs.

The profiling of cancer cell secretomes is considered to be a good strategy for identifying cancer-related biomarkers, but few studies have focused on identifying low-molecular-mass (LMr) proteins (in vitro. Collectively, our data indicate that the tricine–SDS-gel/LC–MS/MS approach can be used to efficiently identify LMr proteins from OSCC cell secretomes and suggest that HMGA2 and MIF could be potential tissue biomarkers for OSCC.

A sensitive liquid chromatographic–tandem mass spectrometry(LC–MS[sol ]MS) method was developed for the determination of rizatriptan in human plasma. The analytes were extracted from plasma samples by liquid–liquid extraction, separated on a Zorbax XDB C8 column (150 × 4.6 mm i.d.) and detected by tandem mass spectrometry with an electrospray ionization interface. Zomitriptan was used as the internal standard. The method had a lower limit of quantitation of 50 pg[sol ]mL for rizatriptan, which showed more sensitivity and speed of analysis compared with reported methods. The within- and between-day precision was measured to be below 11.71% and accuracy between −5.87 and 0.86% for all quality control samples. This quantitation method was successfully applied to the evaluation of the pharmacokinetic profiles of rizatriptan after single oral administration of 5, 10 and 15 mg rizatriptan tablets to 10 healthy volunteers (five males and five females). Copyright © 2005 John Wiley & Sons, Ltd.

10-Hydroxycamptothecin (HCPT), a plant alkaloid isolated from Camptotheca acuminate, is known as a planted-derived insecticide, however, the specific mechanism in insect cells is still unclear. In this study, we treated the ovarian cell line of the silkworm, BmN-SWU1, with different HCPT doses for durations ranging from 0 to 72h. The apoptosis morphology was evident after 72h of incubation and included cell protuberance, concentrated cytoplasm and apoptotic bodies. We observed DNA fragmentation and cell apoptosis after HCPT treatment. The disruption of mitochondrial distribution, activation of the intracellular mitochondrial permeability transition pore, and release of cytochrome c during HCPT-induced apoptosis in dose and time-dependent manner indicate the involvement of mitochondria in BmN-SWU1 cells. Caspase-9 and -3 activities increased gradually with the duration of incubation time. In conclusion, HCPT has a significant effect to initiate the intrinsic mitochondrial pathway in silkworm cells, providing a theoretical basis for better application of plant-derived insecticide in pest control.

In this study we identified a potential pro-apoptotic caspase gene, Bombyx mori(B. mori)ICE-2 (BmICE-2) which encoded a polypeptide of 284 amino acid residues, including a (169)QACRG(173) sequence which surrounded the catalytic site and contained a p20 and a p10 domain. BmICE-2 expressed in Escherichia coli (E. coli) exhibited high proteolytic activity for the synthetic human initiator caspase-9 substrates Ac-LEHD-pNA, but little activity towards the effector caspase-3 substrates Ac-DEVD-pNA. When BmICE-2 was transiently expressed in BmN-SWU1 silkworm B. mori cells, we found that the high proteolytic activity for Ac-LEHD-pNA triggered caspase-3-like protease activity resulting in spontaneous cleavage and apoptosis in these cells. This effect was not replicated in Spodoptera frugiperda 9 cells. In addition, spontaneous cleavage of endogenous BmICE-2 in BmN-SWU1 cells could be induced by actinomycin D. These results suggest that BmICE-2 may be a novel pro-apoptotic gene with caspase-9 activity which is involved apoptotic processes in BmN-SWU1 silkworm B. mori cells.

Aim To describe an Asian population with isolated cutaneous Langerhans cell histiocytosis (LCH), presenting a review on previous studies on this subgroup of patients and comparing our cohort with other studies of cutaneous LCH with systemic involvement. Methods All patients diagnosed as LCH with cutaneous involvement presenting to a tertiary paediatric hospital (KK Women's & Children's Hospital) between January 2001 and December 2011 were reviewed. Information recorded included clinical presentation, investigation results, treatment and outcome. Results We identified 10 patients with cutaneous manifestations of LCH. Six had isolated cutaneous LCH with no visceral or bony involvement, while four had cutaneous lesions with involvement of other organ systems. Of the patients with isolated skin involvement, three were treated with surgical excision, one with topical corticosteroids and two with multi-agent chemotherapy. The four patients with concomitant systemic involvement were treated with multi-agent chemotherapy. None of our patients with isolated cutaneous LCH progressed to multisystem disease during the follow-up period. Conclusion Cutaneous LCH, with or without other organ involvement at diagnosis has a good overall prognosis. However, long-term follow-up is recommended in view of possible recurrence.

Classic eosinophilic pustular folliculitis (EPF), otherwise known as Ofugi disease, is a rare condition commonly treated with topical glucocorticosteroids. If this fails, oral indomethacin is frequently the next line. Because the condition is recurrent, the use of long term steroids may cause side effects such as skin atrophy, hypertrichosis, and dyspigmentation. Topical tacrolimus is an immunosuppressant that is generally used as a steroid-sparing agent in atopic dermatitis. We report a case of classic EPF, which was recurrent over 5 years that had failed topical glucocorticosteroids but was successfully treated with topical tacrolimus 0.1 percent ointment.

Background Rotavirus is one of the leading causes of diarrhoea in children in both developed and developing countries, resulting in an estimated 600 000 deaths worldwide each year. In China, roughly 13 400 children younger than 5 years die from rotavirus infection each year. We aimed to isolate and characterise a human virus for use as a candidate human inactivated rotavirus vaccine strain. We studied the preparation of the vaccine and assessed its immunogenicity effectiveness. Methods From September, 2009, to November, 2012, we collected 206 stool specimens from children in Yunnan, China, and tested for the presence of rotaviruses by use of enzyme immunoassay and double-stranded RNA-PAGE. G and P typing of the positive samples were done by one-step RT-PCR and sequencing. A new human rotavirus was isolated from a child aged 3 months with acute gastritis from the First People's Hospital of Zhaotong City, Zhaotong, China, and was designated ZTR-68. We did a full genomic analysis of ZTR-68 and tested for identifiable characteristics of the virus. A scalable inactivated rotavirus vaccine was cultured by rolling bottles, purified using low-velocity centrifuge, microfiltration clarification, ultrafiltration concentration, and size-exclusion chromatography, and inactivated by the addition of formaldehyde. Its immunogenicity was studied in Balb/c mice by intramuscular injection. Findings Strain ZTR-68 was isolated and plaque purified, and its complete genome was sequenced. ZTR-68 is a rotavirus A of genotype G1P[8] and has a close phylogenetic relation to Wa. We confirmed that our rotavirus vaccine was completely inactivated, and rotavirus antigen can be measured by ELISA. After intramuscular injection of the vaccine into BalB/c mice aged 6 weeks, high titres of rotavirus-specific IgG (>20 000) and neutralising activity (roughly 3000) were recovered in the sera of these mice. Interpretation This newly isolated rotavirus, ZTR-68, is being used to establish a new strain of inactivated rotavirus vaccine. Our findings show that the inactivated rotavirus vaccine has good immunogenicity and provide evidence for further clinical development as an alternative candidate vaccine. Funding This research was financially supported by the State Project for Essential Drug Research and Development, the Chinese national "Twelfth Five-Year" plan (project number: 2014ZX09102041004); the National High Technology Research and Development Program ("863" Program) of China (project number: 2012AA02A404); and the Yunnan Research Program of Application Foundation and Advanced Technology, self-raised funds (project number: 2013FZ140).

Anaphase promoting complex cofactor Cdh1 plays a critical role in tumor suppression and genomic stability in cancer. However, its role in chronic myeloid leukemia (CML) remains unclear. We treated both wild-type and imatinib-resistant K562 cells with imatinib or nilotinib and bortezomib, respectively. The siRNAs of Cdh1 and Skp2 were designed and transiently transfected with HiPerFect transfection reagent into CML cells. Expression of Cdh1-Skp2-p27 pathway proteins were detected by Western blotting. Cell cycle, cell apoptosis and cellular morphology were detected by flow cytometry and Wright staining. Our study revealed that Cdh1 was expressed at lower levels in imatinib-resistant CML blast crisis (BC) patients than imatinib-sensitive ones. Moreover, imatinib and bortezomib induced cell cycle quiescence or arrest, upregulation and nuclear relocation of Cdh1 in CML cells. Furthermore, nilotinib and bortezomib resulted in upregulation of Cdh1 in imatinib-resistant CML cells. Conversely, Cdh1 silencing resulted in stabilization of Skp2 and Cdc20, subsequently promoting G1-S transition and formation of multinucleated cells. Our study shows that TKIs and bortezomib can regulate the cell cycle and cell apoptosis via regulation of the expression and redistribution of Cdh1 in CML-BC, which sheds light on the orchestration of crosstalk between TKIs and bortezomib in imatinib-resistant CML-BC. Additionally, Cdh1 tends to play an important role in maintenance of genomic stability, the detailed mechanisms deserve further study.

Inactivated rotavirus vaccine is a safe and effective potential vaccine for the prevention of rotavirus infection among children, but no approved licensed vaccine is available now. In this study, a scalable inactivated rotavirus vaccine, prepared in Vero cells cultured by microcarrier fermentation, inactivated by formalin and absorbed by Al(OH)(3) adjuvant, was vaccinated into the six weeks-old female Balb/c mice by intramuscular injection. After twice immunization at interval of three weeks, both humoral and cell-mediated immune responses were assessed by ELISA, microneutralization assay and EISPOT assay. The results indicated that the scalable inactivated rotavirus vaccines induced not only high serum IgG antibody and neutralizing antibody responses, but Th1 and Th2 cytokine-secreting cell responses in mice immunized by the inactivated rotavirus vaccines. These results suggest that the scalable inactivated rotavirus vaccine has good immunogenicity, which provided the base for the scaled development of inactivated rotavirus vaccine in the future.

Oral sex is widely used in human foreplay, but rarely documented in other animals. Fellatio has been recorded in bonobos Pan paniscus, but even then functions largely as play behaviour among juvenile males. The short-nosed fruit bat Cynopterus sphinx exhibits resource defence polygyny and one sexually active male often roosts with groups of females in tents made from leaves. Female bats often lick their mate's penis during dorsoventral copulation. The female lowers her head to lick the shaft or the base of the male's penis but does not lick the glans penis which has already penetrated the vagina. Males never withdrew their penis when it was licked by the mating partner. A positive relationship exists between the length of time that the female licked the male's penis during copulation and the duration of copulation. Furthermore, mating pairs spent significantly more time in copulation if the female licked her mate's penis than if fellatio was absent. Males also show postcopulatory genital grooming after intromission. At present, we do not know why genital licking occurs, and we present four non-mutually exclusive hypotheses that may explain the function of fellatio in C. sphinx.

Yunfujing is a traditional chinese drug which in earlier studies has been shown to reduce vestibular signs in man on a rotatory chair with coriolis accelerate stimulation. Recently 131 patients were studied including all kinds of peripheral vestibular disturbances. Eighty-nine cases were treated with yunfujing and 42 controls were given armillaria mellea vabi which has the same effect as diphenidol. We found that yunfujing has the same effect as armillaria mellea vabi or diphenidol: the symptoms were reduced in a few days.

Purpose: Acute myeloid leukemia (AML) with t(7;11)(p15;p15), which results in fusion of NUP98 and HOXA9 genes, is rarely seen, especially in Western countries. Till now only few studies about this entity have been reported in literature, and they usually contained limited number of patients and did not have detailed characterization. This study evaluated the clinical and biological features of this group of patients from a large cohort. Methods: From 1994 to 2007, we had comprehensive studies on a total of 536 AML patients. We compared the clinical features and genetic mutations of NPM1, FLT3/ITD, FLT3/TKD, AML1, K-RAS, N-RAS, CEBPA, MLL/PTD, JAK2, PTPN11, and WT1 between patients with and without this translocation. We also characterized the fusion points in patients with this chromosomal abnormality and devised a quantitative real-time PCR to specifically quantify the leukemia cells bearing the genetic fusion. Results: Among the 536 patients, 11 patients (2%) were found to have t(7;11)(p15;p15). Comparing with the others, we found that AML patients bearing this translocation were younger (p=0.044), female predominant (p=0.010), and having a trend of higher lactate dehydrogenase (LDH) level (p=0.071). This group of patients had worse overall survival (OS) (median 13.5 vs. 36.5 month, p=0.005), relapse free survival (RFS) (median 6 vs. 15.5 months, p Conclusion: AML with NUP98-HOXA9 fusion has a characteristic profile in both clinical and biological aspects, and should be regarded as a poor prognostic group.

This project was conducted to obtain metabolic parameters for inhaled 141 CeO 2 in rats, for related dose effect research. Two hundred and forty three rats were exposed nose-only to polydisperse 141 CeO 2 aerosols (activity median aerodynamic diameters of 1.0 μ m in one group and 0.4 μ m in the other), and measurements were made on living and sacrificed animals up to 180 days after inhalation. Immediately after inhalation, about 77% of the initial body burden was in the gastrointestinal (GI) tract, 19% in the lungs, 4% in the nasopharynx (NP) and 0.2% in the trachea (T). Deposits in the NP and T regions were almost completely cleared within 2 days. Retention of 141 Ce in the lungs could be represented by the sum of two exponential functions, with effective half-times of 9.9 and 24.3 days. The fractions associated with each were 70% and 30%, respectively. During the first 60 days after inhalation, the amounts of 141 Ce in the thoracic lymph nodes increased from 0.003% to 0.022% of the initial body burden, and in the femora from 0.009% to 0.020%. Excretion of 141 Ce was mainly via feces.