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We have explored the efficacy of neoadjuvant chemotherapy in association with cytoreductive surgery and postoperative parenteral nutrition support in advanced ovarian cancer patients. The control group received cytoreductive surgery combined with postoperative conventional chemotherapy and fasted after surgery, whereas the treatment group received neoadjuvant chemotherapy combined with cytoreductive surgery and parenteral nutrition. In contrast to the control group, the operation time, hospital stay, amount of intraoperative blood loss, and abdominal fluid accumulation of the treatment group were diminished, the total effectiveness rate was elevated, serum levels of albumin, transferrin, and prealbumin were increased, levels of human epididymal protein 4, vascular endothelial growth factor, and carbohydrate antigen 125 were declined, and the Karnofky Performance Status score was higher. While there was no difference observed in the 1-year survival rate or total incidence of complications between the two groups, the quality of life of patients in the treatment group improved. [ABSTRACT FROM AUTHOR]

Nucleic acid therapeutics are becoming an important drug modality, offering the unique opportunity to address "undruggable" targets, respond rapidly to evolving pathogens, and treat diseases at the gene level for precision medicine. However, nucleic acid therapeutics have poor bioavailability and are chemolabile and enzymolabile, imposing the need for delivery vectors. Dendrimers, by virtue of their well-defined structure and cooperative multivalence, represent precision delivery systems. We synthesized and studied bola-amphiphilic dendrimers for cargo-selective and on-demand delivery of DNA and small interfering RNA (siRNA), both important nucleic acid therapeutics. Remarkably, superior performances were achieved for siRNA delivery with the second-generation dendrimer, yet for DNA delivery with the third generation. We systematically studied these dendrimers with regard to cargo binding, cellular uptake, endosomal release, and in vivo delivery. Differences in size both of the dendrimers and their nucleic acid cargos impacted the cooperative multivalent interactions for cargo binding and release, leading to cargo-adaptive and selective delivery. Moreover, both dendrimers harnessed the advantages of lipid and polymer vectors, while offering nanotechnology-based tumor targeting and redox-responsive cargo release. Notably, they allowed tumor- and cancer cell-specific delivery of siRNA and DNA therapeutics for effective treatment in different cancer models, including aggressive and metastatic malignancies, outperforming the currently available vectors. This study provides avenues to engineer tailor-made vectors for nucleic acid delivery and precision medicine. [ABSTRACT FROM AUTHOR]

Increasing evidence has suggested alternative splicing (AS) is an essential mechanism for tumor initiation and progression. However, the functions of aberrant splicing have not been well understood in hormone therapy-treated breast cancer (HTBC) patients yet. By mining the SpliceSeq data of TCGA, we characterized 138 8 survival-associated AS events (SASEs) that are markedly related to the overall survival (OS) of HTBC patients. Subsequently, a SASE prognostic signature was deduced via the least absolute shrinkage and selection operator (LASSO) and multivariate Cox analysis, and the HTBC patients were stratified into high- and low-risk groups based on the sign ature. The differentially expressed genes between the high- and low-risk patients were enriched with immune response genes. Furthermore, we revealed that B cell infiltration was significantly low in the high-risk patients with single-sample gene set enrichment analysis (ssGSEA), suggesting a link between AS abnormality and B cell infiltration in tumor immune microenvironment (TIME). Next, a similar prognostic signature based on splicing factor expression was deduced using Molecular Taxonomy of Breast Cancer (METABRIC) HTBC patients. When this prognostic signature was applied to stratify HTBC patients in the METABRIC and TCGA cohorts, the high-risk subgroups both had significantly low B cell infiltration in TIME. CIBERSORT analysis further demonstrated plasma cells infiltrated less in TIME. Also, both the AS (P < 0.0001) and SF (P = 0.009) prognostic signatures performed well in predicting OS of HTBC patients. In summary, our study has demonstrated that AS abnormality is a potential cause of B cell infiltration alteration, which is a critical factor for cancer death risks in HTBC patie nts and might be exploited therapeutically in the future. [ABSTRACT FROM AUTHOR]

There is a growing appreciation of the role of lung stem/progenitor cells in the development and perpetuation of chronic lung disease including idiopathic pulmonary fibrosis. Human amniotic epithelial cells (hAECs) were previously shown to improve lung architecture in bleomycin-induced lung injury, with the further suggestion that hAECs obtained from term pregnancies possessed superior anti-fibrotic properties compared with their preterm counterparts. In the present study, we aimed to elucidate the differential effects of hAECs from term and preterm pregnancies on lung stem/progenitor cells involved in the repair. Here we showed that term hAECs were better able to activate bronchioalveolar stem cells (BASCs) and type 2 alveolar epithelial cells (AT2s) compared with preterm hAECs following bleomycin challenge. Further, we observed that term hAECs restored TGIF1 and TGFß2 expression levels, while increasing c-MYC expression despite an absence of significant changes to Wnt/ß-catenin signaling. In vitro, term hAECs increased the average size and numbers of BASC and AT2 colonies. The gene expression levels of Wnt ligands were higher in term hAECs, and the expression levels of BMP4, CCND1 and CDC42 were only increased in the BASC and AT2 organoids co-cultured with hAECs from term pregnancies but not preterm pregnancies. In conclusion, term hAECs were more efficient at activating the BASC niche compared with preterm hAECs. The impact of gestational age and/or complications leading to preterm delivery should be considered when applying hAECs and other gestational tissue-derived stem and stem-like cells therapeutically. [ABSTRACT FROM AUTHOR]

miR-27b is reported to participate in the proliferation and differentiation of hepatic stellate cells (HSCs) and to regulate fat metabolism of rat HSCs by targeting retinoid X receptor α. Our previous study also indicated that the recombinant P40 protein from Schistosoma japonicum (rSjP40) inhibited the activation of HSCs. In this study, we observed the expression of miR-27b in rSjP40-treated LX-2 cells and explored its potential mechanisms. Quantitative real-time PCR showed that rSjP40 inhibits the expression of miR-27b in LX-2 cells. Further results obtained by Western blot and dual-luciferase reporter assay confirmed that miR-27b regulates peroxisome proliferator-activated receptor γ (PPARγ) expression in rSjP40-treated LX-2 cells by targeting the 3′-UTR of PPARγ. 5-AZA-2′-deoxycytidine (5-AZA-dC), which inhibits methylation of HSCs, partially reversed rSjP40-induced down-regulation expression of miR-27b in LX-2 cells. 5-AZA-dC also partially reversed rSjP40-induced up-regulation expression of PPARγ in LX-2 cells. The increased expression of PPARγ in rSjP40-treated LX-2 cells may be partially due to miR-27b methylation. Therefore, our study provides further insight into the mechanism by which rSjP40 inhibits HSC activation and provides a basis for future study of the blocking effect of rSjP40 in liver fibrosis. [ABSTRACT FROM AUTHOR]

This paper is devoted to the asymptotic behaviors of the solution to a reaction-diffusion-advection system in a homogeneous environment with fixed boundary or free boundary. For the fixed boundary problem, the global asymptotic stability of nonconstant semi-trivial states is obtained. It is also shown that there exists a stable nonconstant co-existence state under some appropriate conditions. Numerical simulations are given not only to illustrate the theoretical results, but also to exhibit the advection-induced difference between the left and right boundaries as time proceeds. For the free boundary problem, the spreading-vanishing dichotomy is proved, i.e., the solution either spreads or vanishes finally. Besides, the criteria for spreading and vanishing are further established. [ABSTRACT FROM AUTHOR]

Background: Despite advances in neonatal care, bronchopulmonary dysplasia (BPD) remains a significant contributor to infant mortality and morbidity. While human amnion epithelial cells (hAECs) have shown promise in small and large animal models of BPD, there is scarce information on long-term benefit and clinically relevant questions surrounding administration strategy remain unanswered. In assessing the therapeutic potential of hAECs, we investigated the impact of cell dosage, administration routes and timing of treatment in a pre-clinical model of BPD. Methods: Lipopolysaccharide was introduced intra-amniotically at day 16 of pregnancy prior to exposure to 65% oxygen (hyperoxia) at birth. hAECs were administered either 12 hours (early) or 4 days (late) after hyperoxia commenced. Collective lung tissues were subjected to histological analysis, multikine ELISA for inflammatory cytokines, FACS for immune cell populations and 3D lung stem cell culture at neonatal stage (postnatal day 7 and 14). Invasive lung function test and echocardiography were applied at 6 and 10 weeks of age. Results: hAECs improved the tissue-to-airspace ratio and septal crest density in a dose-dependent manner, regardless of administration route. Early administration of hAECs, coinciding with the commencement of postnatal hyperoxia, was associated with reduced macrophages, dendritic cells and natural killer cells. This was not the case if hAECs were administered when lung injury was established. Fittingly, early hAEC treatment was more efficacious in reducing interleukin-1β, tumour necrosis factor alpha and monocyte chemoattractant protein-1 levels. Early hAEC treatment was also associated with reduced airway hyper-responsiveness and normalisation of pressure-volume loops. Pulmonary hypertension and right ventricle hypertrophy were also prevented in the early hAEC treatment group, and this persisted until 10 weeks of age. Conclusions: Early hAEC treatment appears to be advantageous over late treatment. There was no difference in efficacy between intravenous and intratracheal administration. The benefits of hAEC administration resulted in long-term improvements in cardiorespiratory function. [ABSTRACT FROM AUTHOR]

Recent advances in saliency detection have used deep learning to obtain high-level features to detect salient regions. These advances have demonstrated superior results over previous works that use handcrafted low-level features for saliency detection. We propose a convolutional neural network (CNN) model to learn high-level features for saliency detection. Compared to other methods, our method presents two merits. First, when performing features extraction, apart from the convolution and pooling step in our method, we add restricted Boltzmann machine into the CNN framework to obtain more accurate features in intermediate step. Second, in order to avoid manual annotation data, we add deep belief network classifier at the end of this model to classify salient and nonsalient regions. Quantitative and qualitative experiments on three benchmark datasets demonstrate that our method performs favorably against the state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Background: Human amnion epithelial cells (hAECs) are clonogenic and have been proposed to reduce inflammatoryinduced tissue injury. Perturbation of the immune response is implicated in the pathogenesis of perinatal brain injury; modulating this response could thus be a novel therapy for treating or preventing such injury. The immunomodulatory properties of hAECs have been shown in other animal models, but a detailed investigation of the effects on brain immune cells following injury has not been undertaken. Here, we investigate the effects of hAECs on microglia, the first immune responders to injury within the brain. Methods: We generated a mouse model combining neonatal inflammation and perinatal hyperoxia, both of which are risk factors associated with perinatal brain injury. On embryonic day 16 we administered lipopolysaccharide (LPS), or saline (control), intra-amniotically to C57Bl/6 J mouse pups. On postnatal day (P)0, LPS pups were placed in hyperoxia (65% oxygen) and control pups in normoxia for 14 days. Pups were given either hAECs or saline intravenously on P4. Results: At P14, relative to controls, LPS and hyperoxia pups had reduced body weight, increased density of apoptotic cells (TUNEL) in the cortex, striatum and white matter, astrocytes (GFAP) in the white matter and activated microglia (CD68) in the cortex and striatum, but no change in total microglia density (Iba1). hAEC administration rescued the decreased body weight and reduced apoptosis and astrocyte areal coverage in the white matter, but increased the density of total and activated microglia. We then stimulated primary microglia (CD45lowCD11blow+) with LPS for 24 h, followed by co-culture with hAEC conditioned medium for 48 h. hAEC conditioned medium increased microglial phagocytic activity, decreased microglia apoptosis and decreased M1 activation markers (CD86). Stimulating hAECs for 24 h with LPS did not alter release of cytokines known to modulate microglia activity. Conclusions: These data demonstrate that hAECs can directly immunomodulate brain microglia, probably via release of trophic factors. This observation offers promise that hAECs may afford therapeutic utility in the management of perinatal brain injury. [ABSTRACT FROM AUTHOR]

The major cell types expressing Golli in the immune system are the T-lineage cells. The aim of the current study was to investigate the changes of gene expression in T lymphocytes subsequent to downregulation of the Golli-myelin basic protein (MBP) gene. RNA interference technology was used to suppress the expression of Golli-MBP in Jurkat cells and DNA microarray techniques were applied to investigate the alterations of gene expression profiles. The results indicated that there were 387 differentially expressed genes. In the Golli-MBP knockdown Jurkat cells, the expression of 108 genes was enhanced, 279 genes were suppressed. Gene ontology analysis identified differentially expressed genes involved in several biological progresses, including cell adhesion and immune responses. Pathway analysis demonstrated that the majority of the differentially expressed genes (23.3%) were involved in cytokine-cytokine receptor interaction. Subsequent to Golli-MBP knockdown, the mechanisms that changed the biological characteristics of Jurkat cells were complex, involving numerous types of functional proteins, and metabolic and signaling pathways. However, further experiments are required to confirm these results. [ABSTRACT FROM AUTHOR]

A 24-year-old female who was previously diagnosed with an immature, right ovarian teratoma was referred to The Second Hospital of Dalian Medical University (Dalian, China) due to abdominal pain. The patient had previously undergone a laparotomy and right ovarian oophorectomy. Despite this, at 10 years post-surgery, the patient developed extensive abdominal metastases, in conjunction with elevated serum cancer antigen (CA)-125 and CA19-9 levels. The patient had a high risk of recurrence, and the liver and spleen metastases were subsequently diagnosed as mature teratomas. In order to prevent the possibility of disease recurrence, frequent post-surgical follow-up, consisting of imaging analysis and the testing of serum markers, is required. Regarding the published literature, there have been no other patients presenting with a giant teratoma with associated metastasis. Due to the lack of regular follow-up appointments in China, the tumor in the present study was not recognized until too late. Therefore, to increase the successful detection of recurrent teratomas, a longer follow-up period is necessary for patients who present with a high risk of recurrence. [ABSTRACT FROM AUTHOR]

Introduction: Conventional antidepressants, including fluoxetine, have a major disadvantage in delayed onset of efficacy. Yueju, an herbal medicine used to treat mood disorders was recently found to exhibit rapid antidepressant effects. The present study was conducted to evaluate the role of Yueju in rapidly acting on major depressive disorder (MDD). Methods: Participants were MDD patients with scores of 24-item Hamilton Depression Rating Scale (HDRS-24) ≥20 and without history of antidepressant use. They randomly received daily oral doses of Yueju (23 g/day) plus fluoxetine (20 mg/day) (experimental group) or placebo plus fluoxetine (control group) for 7 days. HDRS-24 was used as the primary outcome measurement at baseline, and on days 1, 3, 5, and 7. Concentrations of serum brain-derived neurotrophic factor (BDNF) were assessed at baseline and on days 1 and 7. Results: In all, 18 participants met the criteria for data analysis. Compared to baseline level, only experimental group showed significant decrease of HDRS-24 score from day 3 to day 7 (P<0.05). Experimental group also showed significant improvement compared with control group from day 3 to day 7 (P<0.05). No correlation between treatment outcomes with serum BDNF levels was observed. However, experimental group showed significant correlation for serum BDNF level on day 1 with day 7 (r=0.721, P=0.028), whereas the control group did not. Conclusion: Yueju likely contributes to fast-onset antidepressant effects on MDD. Further investigation is necessary to firmly establish the ancient formula as a safe, efficacious, and rapidly acting alternative medicine for MDD treatment. [ABSTRACT FROM AUTHOR]

Background Septin4 (SEPT4) exists widely in human tissues and is related to mechanical stability, actin dynamics, membrane trafficking, viral replication and apoptosis. Data from many studies have suggested that SEPT4 plays a significant role in liver fibrosis. SEPT4 is down-regulated in the model of CCl4 and BDL treated liver fibrosis. However, it is up-regulated and peaked at 12 weeks post-infection (p.i.), and then decreased subsequently in Schistosoma japonicum (S. japonicum) egg-induced liver fibrosis. The aim of this study was to observe the dynamic alteration of SEPT4 after the treatment of praziquantel (PZQ) in ICR mice infected with S. japonicum. Methods Expression of SEPT4 was determined by western blot, immunofluorescence and qRT-PCR. And pro-inflammatory cytokines IL-6 and TNF-α were detected by qRT-PCR. The number of eggs, the diameter of egg granulomas and fibrosis-associated genes were also measured. Results Our results showed that the granulomatous inflammation was reduced, whereafter the expression of SEPT4 on hepatic stellate cells (HSCs) was decreased after PZQ anti-schistosome therapy. And the variation tendency of SEPT4 had positive correlation with the inflammatory response in the area of S. japonicum egg granulomas. Conclusions Based on these findings, the inhibition of the expression of the SEPT4 by PZQ might be due to alleviation of the inflammatory response at the chronic and advanced stage of S. japonicum infection. [ABSTRACT FROM AUTHOR]

The severely preterm infant receives a multitude of life-saving interventions, many of which carry risks of serious side effects. Cell therapy is an important and promising arm of regenerative medicine that may address a number of these problems. Most forms of cellular therapy use stem/progenitor cells or stem-like cells, which have the capacity to migrate, engraft and exert anti-inflammatory effects. Although some of these cell-based therapies have made their way to clinical trials in adults, little headway has been made in the neonatal patient group. This review discusses the efficacy of cell therapy in preclinical studies to date and their potential applications to diseases that afflict many prematurely bom infants. Specifically, we identify the major hurdles that must be overcome before cell therapies can be safely used in the neonatal intensive care unit. [ABSTRACT FROM AUTHOR]

Background: In the process of hepatic fibrosis, hepatic stellate cells (HSCs) can be activated by many inflammatory cytokines. The transforming growth factor-β1 (TGF-β1) is one of the main profibrogenic mediators. Recently, some studies have also shown that microRNAs (miRNAs) play essential roles in the progress of liver fibrosis by being involved in the differentiation, fat metabolism and ECM production of HSCs. Methods: The expression of miR-454 in LX-2 cells treated with TGF-β1 and in the fibrotic livers with Schistosoma japonicum infection was detected by qRT-PCR. The role of miR-454 on LX-2 cells was then analyzed by Western blot, flow cytometry and luciferase assay. Results: The results showed that the expression of miR-454 was down-regulated in the TGF-β1-treated LX-2 cells and miR-454 could inhibit the activation of HSCs by directly targeting Smad4. However, we found that miR-454 had no effect on cell cycle and cell proliferation in TGF-β1-treated LX-2. Besides these, miR-454 was found to be regulated in the process of Schistosoma japonicum infection. Conclusions: All the results suggested that miR-454 could provide a novel therapeutic approach for treating liver fibrosis, especially the liver fibrosis induced by Schistosoma japonicum. [ABSTRACT FROM AUTHOR]

Applying the B3LYP calculations, the reactivity and sensitivity of a graphyne-like BN sheet (BN-yne) were explored toward NO 2 gas. The NO 2 molecule preferentially adsorbs via its both oxygen atoms simultaneously on two B atoms of both –B N– linkage and hexagonal ring with adsorption energy of −12.5) kcal/mol. The NO 2 gas increases the electrical conductance of BN-yne sheet by stabilizing the LUMO level. The electrical conductance of NO 2 /BN-yne complex is predicted to be much higher than that of the pristine BN-yne nanosheet. We showed that the NO 2 gas interacts faster and stronger than the SO 2, NH 3 , CO 2 , O 2 , H 2 O, and N 2 gases with the BN-yne sheet, quickly occupying the adsorption sites. Therefore, we conclude that the BN-yne sheet may be promising selective sensor for NO 2 gas in the presence of these gases. The recovery time for NO 2 desorption from the surface of BN-yne is predicted to be 0.14 ms at room temperature, indicating a short time. [ABSTRACT FROM AUTHOR]

Type II topoisomerases (TOP2) form transient TOP2 cleavage complexes (TOP2ccs) during their catalytic cycle to relieve topological stress. TOP2ccs are covalently linked TOP2-DNA intermediates that are reversible but can be trapped by TOP2 poisons. Trapped TOP2ccs block transactions on DNA and generate genotoxic stress, which are the mechanisms of action of TOP2 poisons. How cells avoid TOP2cc accumulation remains largely unknown. In this study, we uncovered RAD54 like 2 (RAD54L2) as a key factor that mediates a TOP2-specific DNA damage avoidance pathway. RAD54L2 deficiency conferred unique sensitivity to treatment with TOP2 poisons. RAD54L2 interacted with TOP2A/TOP2B and ZATT/ZNF451 and promoted the turnover of TOP2 from DNAwith or without TOP2 poisons. Additionally, inhibition of proteasome activity enhanced the chromatin binding of RAD54L2, which in turn led to the removal of TOP2 from chromatin. In conclusion, we propose that RAD54L2-mediated TOP2 turnover is critically important for the avoidance of potential TOP2-linked DNA damage under physiological conditions and in response to TOP2 poisons. [ABSTRACT FROM AUTHOR]

Backgrounds and aims: Family dysfunction is a significant risk factor for adolescent problematic gaming, yet few studies have investigated the bidirectional relations between changes in family dysfunction and adolescent problematic gaming and potential mediating mechanisms. This study thus examined the bidirectional relations between family dysfunction and adolescent problematic gaming and the mediating role of self-concept clarity within this relation. Methods: Participants included 4,731 Chinese early adolescents (44.9% girls; M age = 10.91 years, SD = 0.72) who were surveyed at four time points 6 months apart. Results: Random intercept cross-lagged panel modeling found (a) family dysfunction directly predicts increased problematic gaming, (b) adolescent problematic gaming directly predicts increased experience of family dysfunction, (c) family dysfunction indirectly predicts problematic gaming via self-concept clarity, and (d) adolescent problematic gaming indirectly predicts family dysfunction via self-concept clarity. Discussion and conclusions: The present study suggests that adolescents may be trapped in a vicious cycle between family dysfunction and problematic gaming either directly or indirectly through impairing their self-concept clarity. Findings indicate fostering youth self-concept clarity is essential to break the vicious circle between dysfunctional experiences in the family and problematic gaming among adolescents. [ABSTRACT FROM AUTHOR]

The regiospecific synthesis of three quercetin O-β-glucosides of N-acetylglucosamine has been achieved in good yield. Selective di- and tri-O-benzylation of quercetin followed by O-glycosylation with 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl chloride under phase-transfer catalysis conditions yielded, after deacetylation and debenzylation, 3-, 3'- and 4'-glycosylated quercetin. [ABSTRACT FROM AUTHOR]

The inhibition of the activation of hepatic stellate cells (HSCs) and the induction of their apoptosis have been investigated as potential strategies to counteract the development and progression of liver fibrosis. Previous research has suggested that apoptosis‑related protein in the transforming growth factor‑β signaling pathway (ARTS) may serve a significant role in numerous cell types; however, little is known regarding its roles in HSCs. Total RNA was extracted from LX‑2 cells, and the human full‑length ARTS gene was obtained by reverse transcription‑polymerase chain reaction and inserted into the pIRES2‑EGFP cloning vector. Subsequently, the recombinant pIRES2‑EGFP‑ARTS plasmid was transfected into LX‑2 cells by FuGENE 6 transfection reagent, and the expression of ARTS was detected by western blotting and fluorescent microscopy. In addition, the effects of pIRES2‑EGFP‑ARTS on the activation, apoptosis, viability and migration of LX‑2 cells were assessed by western blot analysis, TUNEL staining, an MTT assay, and scratch and Transwell assays, respectively. The present results demonstrated that the pIRES2‑EGFP‑ARTS vector expressing human ARTS was successfully constructed, and the overexpression of ARTS contributed to enhance the apoptosis and inhibit the activation of human LX‑2 HSCs. The present findings suggested that ARTS overexpression may have potential as a novel therapeutic strategy to reverse hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Real world activities can be found all around the web. In this paper, we present our work on an exploratory activity search system that is utilizing common-sense data to enrich the search for activities in the web. Two algorithms are proposed. One is the weighted query expansion algorithm using ConceptNet, and the other is the ranking algorithm using query expansion result whose weights are tuned by the genetic algorithms. Finally, a detailed double-blinded user evaluation of the system follows, where we simultaneously evaluate the activity search system from the viewpoint of novelty, serendipity, usefulness and interest. There were 20 participants in this evaluation, and the proposed system has shown a 13.4% increase in novelty and 11.6% increase in serendipity when compared with Bing search. [ABSTRACT FROM AUTHOR]

Nano-cathodoluminescence (Nano-CL) reveals optical emission from individual InGaN quantum wells for applications in optoelectronic devices. We show the luminescent intensity decays over time with exposure to the electron beam for energies between 80 and 200 keV. Measurements of the CL intensity over time show an exponential decline in intensity, which we propose is due to the formation of nitrogen Frenkel defects. The measured CL damage decreases with reductions in the electron accelerating voltage and we suggest that the electron induced structural damage may be suppressed below the proposed damage threshold. The electron beam induced damage leads to a non-radiative region that extends over the measured minority carrier diffusion length. Nano-CL may thus serve as a powerful technique to study III-nitride optoelectronics. [ABSTRACT FROM AUTHOR]

Plant trichomes and root hairs are powerful models for the study of cell fate determination. In Arabidopsis thaliana, trichome and root hair initiation requires a combination of three groups of proteins, including the WD40 repeat protein TRANSPARENT TESTA GLABRA1 (TTG1), R2R3 repeat MYB protein GLABRA1 (GL1), or WEREWOLF (WER) and the IIIf subfamily of basic helix-loop-helix (bHLH) protein GLABRA3 (GL3) or ENHANCER OF GLABRA3 (EGL3). The bHLH component acts as a docking site for TTG1 and MYB proteins. Here, we isolated a mutant showing defects in trichome and root hair patterning that carried a point mutation (R173H) in AtMYC1 that encodes the fourth member of IIIf bHLH family protein. Genetic analysis revealed partial redundant yet distinct function between AtMYC1 and GL3/EGL3. GLABRA2 (GL2), an important transcription factor involved in trichome and root hair control, was down-regulated in Atmyc1 plants, suggesting the requirement of AtMYC1 for appropriate GL2 transcription. Like its homologs, AtMYC1 formed a complex with TTG1 and MYB proteins but did not dimerized. In addition, the interaction of AtMYC1 with MYB proteins and TTG1 was abrogated by the R173H substitution in Atmyc1-1. We found that this amino acid (Arg) is conserved in the AtMYC1 homologs GL3/EGL3 and that it is essential for their interaction withMYBproteins and for their proper functions. Our findings indicate that AtMYC1 is an important regulator of trichome and root hair initiation, and they reveal a novel amino acid necessary for protein-protein interactions and gene function in IIIf subfamily bHLH transcription factors. [ABSTRACT FROM AUTHOR]

AbstractHighly pathogenic avian influenza H5N1 virus represents a growing threat for an influenza pandemic. Development of effective vaccines for H5N1 is a priority for pandemic preparedness. Focusing on influenza virus-like particles (VLPs) has been suggested as a promising vaccine approach. Recent VLP vaccination efforts have been concentrated on the H5N1 strains isolated from humans. Because all confirmed cases of human H5N1 infection were directly transmitted from infected poultry, it is of interest to develop VLP vaccines comprised of antigenic proteins of avian H5N1 strains in order to compare their efficacy in fighting diverse H5N1 strains with vaccines developed using human isolates. In this study, we generated a VLP vaccine composed of the HA, NA, and M1 proteins of the avian H5N1 influenza virus isolate A/chicken/Hubei/489/2004, which seems to occupy a unique phylogenetic position; it belongs to neither clade 1 nor clade 2. Upon infection of Sf9 insect cells using recombinant baculoviruses, the co-expressed HA, NA, and M1 proteins self-assembled and released into the culture medium as VLPs. In a mouse model, purified VLPs elicited an effective antibody response and conferred complete protection against heterologous human H5N1 influenza virus, as well as a homologous avian H5N1 influenza virus isolate. Our work provides further evidence that vaccination with influenza VLPs may be a productive approach to achieve protection against diverse H5N1 strains. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the neuroprotective effects of phenylethanol glycosides (PhGs) on H2O2- and β-amyloid peptide (Aβ)1-42-induced injury of PC12 cells as an in vitro model of Alzheimer's disease (AD). The optimal induction conditions were established through screening of various incubation times and concentrations. PC12 cells were treated with 0.5 μM Aβ1-42 and H2O2 in the presence of PhGs for 24 h and the cell viability was then evaluated by an MTT assay; lactate dehydrogenase (LDH) release and malondialdehyde (MDA) content were also measured. The optimal conditions for establishing the AD model were the treatment of PC12 cells with 0.5 μM Aβ1-42 for 48 h, or with 25 μM H2O2 dissolved in DMEM with PBS. PhGs at concentrations of 5, 25 and 50 μg/ml increased the viability and decreased LDH and MDA release by PC12 cells injured with Aβ1-42 or H2O2. In conclusion, the model of Aβ1-42- and H2O2-induced PC12 cell injury was successfully established. PhGs were shown to have a significant neuroprotective effect against Aβ1-42- or H2O2-induced cell injury. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that oncogenic viral protein plays a crucial role in activating aerobic glycolysis during tumorigenesis, but the underlying mechanisms are largely undefined. Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a transmembrane protein with potent cell signaling properties and has tumorigenic transformation property. Activation of NF-κB is a major signaling pathway mediating many downstream transformation properties of LMP1. Here we report that activation of mTORC1 by LMP1 is a key modulator for activation of NF-κB signaling to mediate aerobic glycolysis. NF-κB activation is involved in the LMP1-induced upregulation of glucose transporter 1 (Glut-1) transcription and growth of nasopharyngeal carcinoma (NPC) cells. Blocking the activity of mTORC1 signaling effectively suppressed LMP1-induced NF-κB activation and Glut-1 transcription. Interfering NF-κB signaling had no effect on mTORC1 activity but effectively altered Glut-1 transcription. Luciferase promoter assay of Glut-1 also confirmed that the Glut-1 gene is a direct target gene of NF-κB signaling. Furthermore, we demonstrated that C-terminal activating region 2 (CTAR2) of LMP1 is the key domain involved in mTORC1 activation, mainly through IKKβ-mediated phosphorylation of TSC2 at Ser939. Depletion of Glut-1 effectively led to suppression of aerobic glycolysis, inhibition of cell proliferation, colony formation, and attenuation of tumorigenic growth property of LMP1-expressing nasopharyngeal epithelial (NPE) cells. These findings suggest that targeting the signaling axis of mTORC1/NF-κB/Glut-1 represents a novel therapeutic target against NPC. IMPORTANCE: Aerobic glycolysis is one of the hallmarks of cancer, including NPC. Recent studies suggest a role for LMP1 in mediating aerobic glycolysis. LMP1 expression is common in NPC. The delineation of essential signaling pathways induced by LMP1 in aerobic glycolysis contributes to the understanding of NPC pathogenesis. This study provides evidence that LMP1 upregulates Glut-1 transcription to control aerobic glycolysis and tumorigenic growth of NPC cells through mTORC1/NF-κB signaling. Our results reveal novel therapeutic targets against the mTORC1/NF-κB/Glut-1 signaling axis in the treatment of EBV-infected NPC. [ABSTRACT FROM AUTHOR]

The primary aim of the present study was to develop a novel microemulsion (ME) formulation to deliver phenylethanoid glycoside (PG) for use in skin lighteners and sunscreens. The oil phase was selected on the basis of drug solubility, while the surfactant and cosurfactant were screened and selected on the basis of their solubilizing capacity and the efficiency with which they formed MEs. Pseudoternary phase diagrams were constructed to evaluate ME regions and five formulations of oil-in-water MEs were selected as vehicles. In vitro skin permeation experiments were performed to optimize the ME formulation and to evaluate its permeability in comparison to that of saline solution. The physicochemical properties of the optimized ME and the permeating ability of PG delivered by this ME were also investigated. The optimized ME formulation was composed of isopropy myristate (7%, w/w), Cremorphor EL (21%, w/w), propylene glycol (7%, w/w) and water (65%, w/w). The cumulative amount of PG that permeated through excised mouse skin when carried by ME was ∼1.68 times that when PG was carried by saline solution only. The cumulative amount of PG in the microemulsion (4149.650±37.3 μg'cm-2) was significantly greater than that of PG in the saline solution (2288.63±20.9 μg'cm-2). Furthermore, the permeability coefficient indicated that optimized microemulsion was a more efficient carrier for transdermal delivery of PG than the control solution (8.87±0.49 cm/hx10-3 vs. 5.41±0.12 cm/hx10-3). Taken together, the permeating ability of ME-carried PG was significantly increased compared with saline solution. [ABSTRACT FROM AUTHOR]

A series of novel reduction-responsive micelles with tailored size were designed and prepared to release doxorubicin (DOX) for treating glioma, which were developed based on amphiphilic block copolymer poly (2-ethyl-2-oxazoline)-b-poly (ε-caprolactone) (PEtOz-SS-PCL) and the micelle size could be regulated by designing the polymer structure. The DOX-loaded PEtOz-SS-PCL micelles had small size and rapid drug release in reductive intracellular environments. Biodistribution andin vivoimaging studies in C6 glioma mice tumor model showed that DOX loaded PEtOz-SS-PCL43 micelles with the smallest size had superior accumulation and fast drug release in tumor sites.In vivoantitumor activity demonstrated that DOX-loaded PEtOz-SS-PCL43 micelles improved antitumor efficacy in contrast to PEtOz-SS-PCL micelles with larger size toward the orthotopic C6-Luci cells-bearing mice. This study shows great potential in tailoring the micelle size and introducing the responsive bonds or compartment for intracellular drug delivery and release in glioma treatment by designing the architecture of the polymer. [ABSTRACT FROM AUTHOR]

Understanding the photocatalytic conversion mechanism of NO is crucial to develop an effective and practical strategy for indoor air pollution control. In this study, we systematically investigated the photocatalytic removal mechanism of NO over nanocrystalline Bi2Sn2O7, which was successfully synthesized via hydrothermal method using bismuth citrate and stannic chloride pentahydrate as precursors for the first time. Various characterizations were carried out to study the physicochemical properties of the as-prepared samples. The performance of the as-prepared Bi2Sn2O7 samples was evaluated by the photocatalytic degradation of NO in a continuous reactor under simulated solar light irradiation. The NO removal rate over the Bi2Sn2O7 sample synthesized for 12 h (BSO-12) was 37%, which was much higher than those of Bi2Sn2O7 samples synthesized for 24 h (BSO-24) and 36 h (BSO-36). Results from photocurrent tests and electrochemical impedance spectroscopy (EIS) demonstrated that the BSO-12 sample presents much more effective interface charge separation efficiency, which can contribute to its improved photocatalytic performance. Reactive radicals during the photocatalysis processes were identified via trapping experiments, which were also confirmed by electron spin resonance (ESR) study. Combined with the quantification of reaction intermediates, the photocatalytic removal mechanism of NO over nanocrystalline Bi2Sn2O7 was proposed for the first time. [ABSTRACT FROM AUTHOR]

Phosphorylation and dephosphorylation of the checkpoint kinase CaRad53 is crucial for fungal cells in response to genotoxic stresses. The protein phosphatase 2A (PP2A) CaPph3/CaPsy2 phosphatase complex is involved in CaRad53 dephosphorylation in Candida albicans. In view of the role of ScTip41/ScTap42 in regulating PP2A phosphatases in Saccharomyces cerevisiae, we have explored the function of CaTip41 in C. albicans. Here, we show that CaTIP41 is a functional ortholog of ScTIP41 in the sensitivity of S. cerevisiae cells to rapamycin. Deletion of CaTIP41 causes C. albicans cells to be sensitive to DNA damaging agents, methylmethane sulfonate (MMS) and cisplatin, and resistant to both rapamycin and caffeine. Accordingly, expression of CaTip41 increases in response to MMS and cisplatin. In addition, C. albicans cells lacking CaTIP41 show a delay in the recovery from MMS-induced filamentation to yeast form, decreased PP2A activity and a defect in deactivation of CaRad53 during recovery from DNA damage. Through yeast two-hybrid assay we show that CaTip41 interacts with either CaPph3, CaPsy2 or CaTap42. Therefore, CaTip41 plays regulatory roles in both the CaRad53 deactivation during recovery from DNA damage and the target of rapamycin signaling pathway. [ABSTRACT FROM AUTHOR]

Nanocathodoluminescence reveals thespectral properties of individual InGaN quantum wells in high efficiencylight emitting diodes. We observe a variation in the emission wavelengthof each quantum well, in correlation with the Si dopant concentrationin the quantum barriers. This is reproduced by band profile simulations,which reveal the reduction of the Stark shift in the quantum wellsby Si doping. We demonstrate nanocathodoluminescence is a powerfultechnique to optimize doping in optoelectronic devices. [ABSTRACT FROM AUTHOR]

This paper describes a detailed analysis of the effects of high temperatures on the optical performance and structural characteristics of GaN-based LED structures with a high threading dislocation density. Results show that, as a consequence of storage at 900 °C in N2 atmosphere, the samples exhibit: (i) an increase in the efficiency of GaN and quantum-well luminescence, well correlated to an increase in carrier lifetime; (ii) a decrease in the parasitic luminescence peaks related to Mg acceptors, which is correlated to the reduction in the concentration of Mg in the p-type region, detected by Secondary Ion Mass Spectroscopy (SIMS); (iii) a diffusion of acceptor (Mg) atoms to the quantum well region; (iv) a reduction in the yield of Rutherford Backscattering Spectrometry (RBS)-channeling measurements, possibly due to a partial re-arrangement of the dislocations, which is supposed to be correlated to the increase in radiative efficiency (see (i)). [ABSTRACT FROM AUTHOR]

A three-step synthesis from genistein of the water-soluble sodium salt of 7-O-carboxymethyl-genistein is described. Base-catalysed reaction of genistein with t-butyl bromoacetate gave 7-O-(carbo-t-butoxy)methyl-genistein, which was hydrolysed by aqueous acetic acid to 7-O-carboxymethyl-genistein and neutralised (NaHCO3) to give the target compound. The carboxylate group enhanced the watersolubility of genistein more than a thousand-fold and the new derivate will be useful as a candidate compound in pharmacological and clinical chemistry studies of isoflavones. [ABSTRACT FROM AUTHOR]

Deep level transient spectroscopy was performed on InGaN/GaN multiple quantum well light emitting diodes (LEDs) in order to determine the effect of the dislocation density on the deep intragap electronic levels. The LEDs were grown by metalorganic vapor phase epitaxy on GaN templates with a high dislocation density of 8 × 109 cm-2 and a low dislocation density of 3 × 108 cm-2. Three trapping levels for electrons were revealed, named A, A1, and B, with energies EA≅0.04 eV, EA1≅0.13 eV, and EB≅0.54 eV, respectively. The trapping level A has a much higher concentration in the LEDs grown on the template with a high density of dislocations. The logarithmic dependence of the peak amplitude on the bias pulse width for traps A and A1 identifies the defects responsible for these traps as associated with linearly arranged defects. We conclude that traps A and A1 are dislocation-related intragap energy levels. [ABSTRACT FROM AUTHOR]