In JoVE (2)

Other Publications (255)

Articles by Kai Wang in JoVE

 JoVE Cancer Research

How to Study Basement Membrane Stiffness as a Biophysical Trigger in Prostate Cancer and Other Age-related Pathologies or Metabolic Diseases

1Departamento de Genética, Facultad de Medicina, Universidad de la República (UDELAR), 2Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, 3School of Biological, Biomedical & Environmental Sciences, University of Hull


JoVE 54230

Other articles by Kai Wang on PubMed

[Whether Free Anterolateral Thigh Flaps Are Suitable for the Elderly Patients with Oral Cancer]

Zhonghua Kou Qiang Yi Xue Za Zhi = Zhonghua Kouqiang Yixue Zazhi = Chinese Journal of Stomatology. Oct, 2015  |  Pubmed ID: 26757629

To identify the factors that were predictive of outcome and to determine the effect of age on perioperative complications.

Conus Medullaris Ganglioneuroma with Syringomyelia Radiologically Mimicking Ependymoma: A Case Report

Oncology Letters. Dec, 2015  |  Pubmed ID: 26788212

Ganglioneuromas are rare, benign, well-differentiated tumors of the conus medullaris. Approximately 20 cases of spinal cord ganglioneuroma, and only 1 case of mixed chemodectoma-ganglioneuroma of the conus medullaris have been previously reported. The present study presents the case of a 38-year-old man with a histopathological diagnosis of conus medullaris ganglioneuroma. The patient presented with hypoesthesia in the lower limbs, muscle atrophy of the right lower limb and dysuria. Magnetic resonance imaging analysis led to a diagnosis of ependymoma. Histopathological analysis of the excised mass revealed typical, well-differentiated ganglion cells, consistent with a ganglioneuroma. The mass was associated with a neighboring syringomyelia. At an 18 month follow-up the patient had recovered, although some remaining difficulty in walking and urinating remained. The aim of the present report was to raise awareness that when ganglioneuromas present in unusual locations, analogous radiological findings may mislead investigators to consider more common pathologies and thus result in misdiagnosis. The present case demonstrates the importance of considering the potential differential diagnoses for neural tissue neoplasms.

Endocan of the Maternal Placenta Tissue is Increased in Pre-eclampsia

International Journal of Clinical and Experimental Pathology. 2015  |  Pubmed ID: 26823798

Pre-eclampsia (PE) is associated with intravascular inflammation and endothelial dysfunction. Interestingly, endocan plays a predominant role in the vascular inflammation and is considered as a biomarker of endothelial dysfunction. The aim of this study was to explore whether the endocan levels in serum and placenta were different between pregnant women with PE and the normal pregnancies.

Duodenal Duplication Manifested by Abdominal Pain and Bowl Obstruction in an Adolescent: a Case Report

International Journal of Clinical and Experimental Medicine. 2015  |  Pubmed ID: 26885132

Duodenal duplication (DD) is a rare congenital anomaly reported mainly in infancy and childhood, but seldom in adolescent and adults. Symptoms, such as abdominal pain, nausea, vomiting or dyspepsia may present depending on the location and type of the lesion. DD can result in several complications, including pancreatitis, bowl obstruction, gastrointestinal bleeding, perforation and jaundice. Surgery is still the optimal method for treatment, although endoscopic fenestration has been described recently. Here, we report a case of a DD on the second portion of the duodenum in a 17-year-old adolescent complaining of transient epigastric pain and vomiting after meal. We suspected the diagnosis of DD by abdominal computerized tomography and endoscopic ultrasonography. We treated her by subtotal excision and internal derivation. Eventually, we confirmed our diagnosis with histopathological result.

[Effects of Renal Denervation on Left Atrial Fibrosis in Rats with Isoproterenol Induced Chronic Heart Failure]

Zhonghua Xin Xue Guan Bing Za Zhi. Dec, 2015  |  Pubmed ID: 26888837

To investigate the effects of renal denervation (RDN) on left atrial fibrosis in rats with chronic heart failure.

[Molecular Detection of Giardia Lamblia and Cryptosporidium Species in Pet Dogs]

Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi = Chinese Journal of Parasitology & Parasitic Diseases. Oct, 2015  |  Pubmed ID: 26931042

To determine the prevalence of Giardia lamblia and Cryptosporidium species infection in pet dogs, and identify the G. lamblia assemblages and Cryptosporidium species.

Clinically Advanced and Metastatic Pure Mucinous Carcinoma of the Breast: a Comprehensive Genomic Profiling Study

Breast Cancer Research and Treatment. Jan, 2016  |  Pubmed ID: 26762307

Pure mucinous breast carcinoma (pmucBC) is a distinctive variant of breast cancer (BC) featuring an excellent overall prognosis. However, on rare occasions, pmucBC pursues an aggressive clinical course. We queried whether comprehensive genomic profiling (CGP) would uncover clinically relevant genomic alterations (CRGA) that could lead to targeted therapy treatment for patients with an advanced and metastatic form of pmucBC.

Long Noncoding RNA GAS5 Can Predict Metastasis and Poor Prognosis: a Meta-analysis

Minerva Medica. Feb, 2016  |  Pubmed ID: 26763654

Growth arrest-specific 5 (GAS5), a newly discovered long-noncoding RNAs (lncRNAs), has been reported to be down-regulated in multiple cancers. This meta-analysis aims to identify the potential value of GAS5 as a biomarker of cancer metastasis and prognosis.

Development of Self-assembling Peptide Nanovesicle with Bilayers for Enhanced EGFR-targeted Drug and Gene Delivery

Biomaterials. Mar, 2016  |  Pubmed ID: 26763734

Development of rational vectors for efficient drug and gene delivery is crucial for cancer treatment. In this study, epidermal growth factor receptor (EGFR)-binding peptide amphiphile (PA) were used as the primary bilayer skeleton material to construct ultra-stable self-assembling peptide nanovesicle (SPV). The resulted EGFR-targeted SPV (ESPV) could efficiently encapsulate therapeutic cargos (drugs or small interfering RNAs [siRNAs]) or labelled fluorescent cargo (quantum dots [QDs]) and exhibited excellent affinity for EGFR-positive cancer cells. Moreover, ESPV could deliver more drug or plasmid DNA to tumour sites and promote gene expression (a three-fold ratio of ESPVs vs cationic liposomes). Notably, the individual delivery or co-delivery of doxorubicin (DOX) and the acetylcholinesterase (AChE) gene via the ESPVs resulted in excellent drug/gene delivery both in vitro and in vivo and exerted a significant growth-suppressing effect on a liver cancer xenograft. This nanoscale, targeted cargo-packaging technology may provide a new strategy for the design of highly targeted cancer therapy vectors.

FLAGS: A Flexible and Adaptive Association Test for Gene Sets Using Summary Statistics

Genetics. Mar, 2016  |  Pubmed ID: 26773050

Genome-wide association studies (GWAS) have been widely used for identifying common variants associated with complex diseases. Despite remarkable success in uncovering many risk variants and providing novel insights into disease biology, genetic variants identified to date fail to explain the vast majority of the heritability for most complex diseases. One explanation is that there are still a large number of common variants that remain to be discovered, but their effect sizes are generally too small to be detected individually. Accordingly, gene set analysis of GWAS, which examines a group of functionally related genes, has been proposed as a complementary approach to single-marker analysis. Here, we propose a FL: exible and A: daptive test for G: ene S: ets (FLAGS), using summary statistics. Extensive simulations showed that this method has an appropriate type I error rate and outperforms existing methods with increased power. As a proof of principle, through real data analyses of Crohn's disease GWAS data and bipolar disorder GWAS meta-analysis results, we demonstrated the superior performance of FLAGS over several state-of-the-art association tests for gene sets. Our method allows for the more powerful application of gene set analysis to complex diseases, which will have broad use given that GWAS summary results are increasingly publicly available.

Highly Fluorescent and Photostable Polymeric Nanofibers As Scaffolds for Cell Interfacing and Long-Term Tracking

Advanced Healthcare Materials. Mar, 2016  |  Pubmed ID: 26773963

Highly fluorescent polymeric nanofibers fabricated via electrospinning of PCL-DPP-PCL (photostable polycaprolactones-di(thiophene-2-yl)-diketopyrrolopyrrole-photostable polycaprolactones) and commercial PCL mixture show superior photostability and cytocompatibility for long-term tracking of cell-substrate interaction. As a proof of concept, these PCL-DPP-PCL nanofibers enable clear visualization of intricate cell-substrate interactions such as oligodendrocyte myelination.

Hydroxylated Polychlorinated Biphenyls in Human Sera from Adolescents and Their Mothers Living in Two U.S. Midwestern Communities

Chemosphere. Mar, 2016  |  Pubmed ID: 26774304

Hydroxylated polychlorinated biphenyls (OH-PCBs) have been detected in human specimens and some are suspected as being more toxic than their parent compounds. We compared 58 OH-PCB congeners (in 51 chromatographic peaks) in serum samples from participants in the AESOP Study, a longitudinal cohort study of adolescents and their mothers living in urban and rural areas in the United States. We hypothesized that adolescents would have lower levels of OH-PCBs than their mothers and that serum concentration of OH-PCBs would be stable over a 3-year period. We found statistically significant differences in total OH-PCBs between age groups in both East Chicago (p = 0.001) and Columbus Junction (p < 0.001), with adolescents having lower concentrations than their mothers. We observed that lower-chlorinated OH-PCBs were rarely detected, suggesting that they are not retained in serum and/or rapidly biotransformed into other forms. Twelve OH-PCBs, including several that are rarely reported (4,4'-diOH-PCB 202, 4'-OH-PCB 208, and 4-OH-PCB 163) were detected in over 60% of participants. Lastly, from repeated measures within subject serum for three OH-PCBs, concentrations of 4-OH-PCB 107 and 4-OH-PCB 187 changed significantly over three years of the study.

Toxic Effects of Thifluzamide on Zebrafish (Danio Rerio)

Journal of Hazardous Materials. Apr, 2016  |  Pubmed ID: 26780700

Thifluzamide is a fungicide widely used to control crop diseases, and it therefore constitutes a hazard to the environment. In this study, zebrafish were selected to assess the aquatic toxicity of thifluzamide. The acute and development toxicity of thifluzamide to embryos, larvae, and adult zebrafish were measured and the corresponding 96h-LC50 values were as follows: adult fish (4.19mg/L)

Identification of Epoxide-Derived Metabolite(s) of Benzbromarone

Drug Metabolism and Disposition: the Biological Fate of Chemicals. Apr, 2016  |  Pubmed ID: 26792818

Benzbromarone (BBR) is a benzofuran derivative that has been quite useful for the treatment of gout; however, it was withdrawn from European markets in 2003 because of reported serious incidents of drug-induced liver injury. BBR-induced hepatotoxicity has been suggested to be associated with the formation of a quinone intermediate. The present study reported epoxide-derived intermediate(s) of BBR. An N-acetylcysteine (NAC) conjugate derived from epoxide metabolite(s) was detected in both microsomal incubations of BBR and urine samples of mice treated with BBR. The NAC conjugate was identified as 6-NAC BBR. Ketoconazole suppressed the bioactivation of BBR to the epoxide intermediate(s), and the CYP3A subfamily was the primary enzyme responsible for the formation of the epoxide(s). The present study provided new information on metabolic activation of BBR.

Molecular Rearrangement of Waxy and Normal Maize Starch Granules During in Vitro Digestion

Carbohydrate Polymers. Mar, 2016  |  Pubmed ID: 26794941

The objective of the present study is to understand the changes in starch structures during digestion and the structures contributing to slow digestion properties. The molecular, crystalline, and granular structures of native waxy maize, normal maize, high-amylose maize, and normal potato starch granules were monitored using SEC, XRD, DSC, and SEM. The amylose and amylopectin molecules of all four starches were hydrolyzed to smaller dextrins, with some having linear molecular structure. Neither the A- nor B-type crystallinity was resistant to enzyme hydrolysis. Starch crystallites with melting temperature above 120°C appeared in waxy and normal maize starches after digestion, suggesting that the linear dextrins retrograded into thermally stable crystalline structure. These crystallites were also observed for high-amylose maize starch before and after digestion, contributing to its low enzyme digestibility. On the contrary, the enzyme-resistant granular structure of native normal potato starch was responsible for its low susceptibility to enzyme hydrolysis.

Identifying the Association Between Contrast Enhancement Pattern, Surgical Resection, and Prognosis in Anaplastic Glioma Patients

Neuroradiology. Apr, 2016  |  Pubmed ID: 26795126

Contrast enhancement observable on magnetic resonance (MR) images reflects the destructive features of malignant gliomas. This study aimed to investigate the relationship between radiologic patterns of tumor enhancement, extent of resection, and prognosis in patients with anaplastic gliomas (AGs).

Polyphyllin VII Induces an Autophagic Cell Death by Activation of the JNK Pathway and Inhibition of PI3K/AKT/mTOR Pathway in HepG2 Cells

PloS One. 2016  |  Pubmed ID: 26808193

Polyphyllin VII (PP7), a pennogenyl saponin isolated from Rhizoma Paridis, exhibited strong anticancer activities in various cancer types. Previous studies found that PP7 induced apoptotic cell death in human hepatoblastoma cancer (HepG2) cells. In the present study, we investigated whether PP7 could induce autophagy and its role in PP7-induced cell death, and elucidated its mechanisms. PP7 induced a robust autophagy in HepG2 cells as demonstrated by the conversion of LC3B-I to LC3B-II, degradation of P62, formation of punctate LC3-positive structures, and autophagic vacuoles tested by western blot analysis or InCell 2000 confocal microscope. Inhibition of autophagy by treating cells with autophagy inhibitor (chloroquine) abolished the cell death caused by PP7, indicating that PP7 induced an autophagic cell death in HepG2 cells. C-Jun N-terminal kinase (JNK) was activated after treatment with PP7 and pretreatment with SP600125, a JNK inhibitor, reversed PP7-induced autophagy and cell death, suggesting that JNK plays a critical role in autophagy caused by PP7. Furthermore, our study demonstrated that PP7 increased the phosphorylation of AMPK and Bcl-2, and inhibited the phosphorylation of PI3K, AKT and mTOR, suggesting their roles in the PP7-induced autophagy. This is the first report that PP7 induces an autophagic cell death in HepG2 cells via inhibition of PI3K/AKT/mTOR, and activation of JNK pathway, which induces phosphorylation of Bcl-2 and dissociation of Beclin-1 from Beclin-1/Bcl-2 complex, leading to induction of autophagy.

Decreased Level of Osteopontin in Children with Allergic Rhinitis During Sublingual Immunotherapy

International Journal of Pediatric Otorhinolaryngology. Feb, 2016  |  Pubmed ID: 26810282

Sublingual immunotherapy (SLIT) is proven to be very effective in the treatment of allergic rhinitis (AR), but its regulatory mechanism and biomarkers for predicting efficacy are still unknown. Osteopontin (OPN), as a recently described Th2 inflammation related protein, plays key role in the pathogenesis of AR. The aim of this study was to identify the expression and role of OPN during SLIT in children.

Lysine Adduction by Reactive Metabolite(s) of Monocrotaline

Chemical Research in Toxicology. Mar, 2016  |  Pubmed ID: 26812400

Pyrrolizidine alkaloids (PAs) are known hepatotoxins. The execution of the toxicities of the alkaloids requires metabolic activation. Protein modification by reactive metabolites of PAs has been suggested to be an important mechanism of the toxic actions of PAs. The objectives of the present study were to define the interactions of dehydromonocrotaline (DHM) with lysine, lysine derivatives, a model peptide, and bovine serum albumin and to explore the lysine modification of hepatic proteins of animals given monocrotaline. DHM was found to react with the ε-amino group of all model compounds tested after incubation with DHM, and the modification reaction preferentially occurred at C7 of the necine base. The lysine residue modification with the same regioselectivity was also observed in hepatic proteins of mice treated with monocrotaline. The observed modification increased with the increase in doses administered to the animals. This work allowed us to better understand the mechanisms of the hepatotoxicity of monocrotaline.

Dysregulated Expression of IDO May Cause Unexplained Recurrent Spontaneous Abortion Through Suppression of Trophoblast Cell Proliferation and Migration

Scientific Reports. 2016  |  Pubmed ID: 26814137

In pregnancy, trophoblast proliferation, migration and invasion are important for the establishment and maintenance of a successful pregnancy. Impaired trophoblast function has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy, but the underlying mechanisms remain unclear. Indoleamine 2,3-dioxygenase (IDO), an enzyme that catabolizes tryptophan along the kynurenine pathway, is highly expressed in the placenta and serum during pregnancy. Here, we identified a novel function of IDO in regulating trophoblast cell proliferation and migration. We showed that IDO expression and activity were decreased in unexplained recurrent spontaneous abortion (URSA) compared to normal pregnancy. Furthermore, blocking IDO in human trophoblast cells led to reduced proliferation and migration, along with decreased STAT3 phosphorylation and MMP9 expression. Increased STAT3 phosphorylation reversed the IDO knockdown-suppressed trophoblast cell proliferation and migration. In addition, the overexpression of IDO promoted cell proliferation and migration, which could be abolished by the STAT3 signaling inhibitor (AG490). Finally, we observed similar reductions of STAT3 phosphorylation and MMP9 expression in URSA patients. These results indicate that the level of IDO expression may be associated with pregnancy-related complications, such as URSA, by affecting trophoblast cell proliferation and migration via the STAT3 signaling pathway.

Quantification of MRNA Levels Using Real-Time Polymerase Chain Reaction (PCR)

Methods in Molecular Biology (Clifton, N.J.). 2016  |  Pubmed ID: 26820946

Real-time quantitative reverse transcription PCR technique has advanced greatly over the past 20 years. Messenger RNA (mRNA) levels in cells or tissues can be quantified by this approach. It is well known that changes in mRNA expression in disease, and correlation of mRNA expression profiles with clinical parameters, serve as clinically relevant biomarkers. Hence, accurate determination of the mRNA levels is critically important in describing the biological, pathological, and clinical roles of genes in health and disease. This chapter describes a real-time PCR approach to detect and quantify mRNA expression levels, which can be used for both laboratorial and clinical studies in breast cancer research.

The Australasian Frog Family Ceratobatrachidae in China, Myanmar and Thailand: Discovery of a New Himalayan Forest Frog Clade

Dong Wu Xue Yan Jiu = Zoological Research / "Dong Wu Xue Yan Jiu" Bian Ji Wei Yuan Hui Bian Ji. Jan, 2016  |  Pubmed ID: 26828029

In an effort to study the systematic affinities and specieslevel phylogenetic relationships of the enigmatic anurans variably assigned to the genera Ingerana or Limnonectes (family Dicroglossidae), we collected new molecular sequence data for five species including four Himalayan taxa, Limnonectes xizangensis, Lim. medogensis, Lim. alpina, [corrected] Ingerana borealis and one southeast Asian species, I. tasanae, and analyzed these together with data from previous studies involving other ostensibly related taxa. Our surprising results demonstrate unequivocally that Lim. xizangensis, Lim. medogensis and Lim. alpina [corrected] form a strongly supported clade, the sister-group of the family Australasian forest frog family Ceratobatrachidae. This discovery requires an expansion of the definition of Ceratobatrachidae and represents the first record of this family in China. These three species are distinguished from the species of Ingerana and Limnonectes by the: (1) absence of interdigital webbing of the foot, (2) absence of terminal discs on fingers and toes, (3) absence of circumarginal grooves on the fingers and toes, and (4) absence of tarsal folds. Given their phylogenetic and morphological distinctiveness, we assign them to the oldest available generic name for this clade, Liurana Dubois 1987, and transfer Liurana from Dicroglossidae to the family Ceratobatrachidae. In contrast, Ingerana tasanae was found to be clustered with strong support with the recently described genus Alcalus (Ceratobatrachidae), a small clade of otherwise Sundaic species; this constitutes a new record of the family Ceratobatrachidae for Myanmar and Thailand. Finally, Ingerana borealis clustered with the "true" Ingerana (family Dicroglossidae), for which the type species is I. tenasserimensis.

A New Genus and Species of Treefrog from Medog, Southeastern Tibet, China (Anura, Rhacophoridae)

Dong Wu Xue Yan Jiu = Zoological Research / "Dong Wu Xue Yan Jiu" Bian Ji Wei Yuan Hui Bian Ji. Jan, 2016  |  Pubmed ID: 26828030

A new genus and species of threefrog is described from Medog, southeastern Tibet, China based on morphological and phylogenetic data. The new genus can be distinguished from other treefrog genera by the following combination of characters: (1) body size moderate, 45.0 mm in male; (2) snout rounded; (3) canthus rostralis obtuse and raised prominently, forming a ridge from nostril to anterior corner of eyes; (4) web rudimentary on fingers; (5) web moderately developed on toes; (6) phalange "Y" shaped, visible from dorsal side of fingers and toes; (7) skin of dorsal surfaces relatively smooth, scatted with small tubercles; (8) iris with a pale yellow, "X" shaped pattern of pigmentation.

A New Species of the Genus Scutiger (Anura: Megophryidae) from Medog of Southeastern Tibet, China

Dong Wu Xue Yan Jiu = Zoological Research / "Dong Wu Xue Yan Jiu" Bian Ji Wei Yuan Hui Bian Ji. Jan, 2016  |  Pubmed ID: 26828031

A new species of Scutiger Theobald, 1868 is described from Medog, southeastern Tibet, China, based on morphological and molecular data. The new species was previously identified as Scutiger nyingchiensis, but it can be differentiated from the latter and all other congeners by the following combination of characters: (1) medium adult body size, SVL 50.5-55.6 mm in males and 53.8-57.2 mm in females; (2) maxillary teeth absent; (3) web rudimentary between toes; (4) prominent, conical-shaped tubercles on dorsal and lateral surfaces of body and limbs; (5) tubercles covered by black spines in both sexes in breeding condition; (6) a pair of pectoral glands and a pair of axillary glands present and covered by black spines in males in breeding condition, width of axillary gland less than 50% of pectoral gland; (7) nuptial spines present on dorsal surface of first and second fingers, and inner side of third finger in males in breeding condition; (8) spines absent on the abdominal region; (9) vocal sac absent. In addition, the distribution and conservation status of the new species are also discussed.

A New Species of the Genus Amolops (Amphibia: Ranidae) from Southeastern Tibet, China

Dong Wu Xue Yan Jiu = Zoological Research / "Dong Wu Xue Yan Jiu" Bian Ji Wei Yuan Hui Bian Ji. Jan, 2016  |  Pubmed ID: 26828032

A new species of the genus Amolops Cope, 1865 is described from Nyingchi, southeastern Tibet, China, based on morphological and molecular data. The new species, Amolops nyingchiensis sp. nov. is assigned to the Amolops monticola group based on its skin smooth, dorsolateral fold distinct, lateral side of head black, upper lip stripe white extending to the shoulder. Amolops nyingchiensis sp. nov. is distinguished from all other species of Amolops by the following combination of characters: (1) medium body size, SVL 48.5-58.3 mm in males, and 57.6-70.7 mm in females; (2) tympanum distinct, slightly larger than one third of the eye diameter; (3) a small tooth-like projection on anteromedial edge of mandible; (4) the absence of white spine on dorsal surface of body; (5) the presence of circummarginal groove on all fingers; (6) the presence of vomerine teeth; (7) background coloration of dorsal surface brown, lateral body gray with yellow; (8) the presence of transverse bands on the dorsal limbs; (9) the presence of nuptial pad on the first finger in males; (10) the absence of vocal sac in males. Taxonomic status of the populations that were previously identified to A. monticola from Tibet is also discussed.

Two New Species of Japalura (Squamata: Agamidae) from the Hengduan Mountain Range, China

Dong Wu Xue Yan Jiu = Zoological Research / "Dong Wu Xue Yan Jiu" Bian Ji Wei Yuan Hui Bian Ji. Jan, 2016  |  Pubmed ID: 26828033

Until recently, the agamid species, Japalura flaviceps, was recognized to have the widest geographic distribution among members of the genus occurring in China, from eastern Tibet to Shaanxi Province. However, recent studies restricted the distribution of J. flaviceps to the Dadu River valley only in northwestern Sichuan Province, suggesting that records of J. flaviceps outside the Dadu River valley likely represent undescribed diversity. During two herpetofaunal surveys in 2013 and 2015, eight and 12 specimens of lizards of the genus Japalura were collected from the upper Nujiang (=Salween) Valley in eastern Tibet, China, and upper Lancang (=Mekong) Valley in northwestern Yunnan, China, respectively. These specimens display a unique suite of diagnostic morphological characters. Our robust comparisons of phenotype reveal that these populations can be distinguished readily from J. flaviceps and all other recognized congeners. Herein, we describe the two Japalura lineages as new species, Japalura laeviventris sp. nov. and Japalura iadina sp. nov.. In addition, we provide updated conservation assessments for the new species as well as imperiled congeners according to the IUCN criteria for classification, discuss the importance of color patterns in the diagnosis and description of species in the genus Japalura, and discuss directions for future taxonomic studies of the group.

AmphibiaChina: an Online Database of Chinese Amphibians

Dong Wu Xue Yan Jiu = Zoological Research / "Dong Wu Xue Yan Jiu" Bian Ji Wei Yuan Hui Bian Ji. Jan, 2016  |  Pubmed ID: 26828034

AmphibiaChina, an open-access, web-based database, is designed to provide comprehensive and up-to-date information on Chinese amphibians. It offers an integrated module with six major sections. Compared to other known databases including AmphibiaWeb and Amphibian Species of the World, AmphibiaChina has the following new functions: (1) online species identification based on DNA barcode sequences; (2) comparisons and discussions of different major taxonomic systems; and (3) phylogenetic progress on Chinese amphibians. This database offers a window for the world to access available information of Chinese amphibians. AmphibiaChina with its Chinese version can be accessed at http://www.amphibiachina.org.

Caffeic Acid Phenethyl Ester Exhibiting Distinctive Binding Interaction with Human Serum Albumin Implies the Pharmacokinetic Basis of Propolis Bioactive Components

Journal of Pharmaceutical and Biomedical Analysis. Apr, 2016  |  Pubmed ID: 26829518

Caffeic acid phenethyl ester (CAPE), as one of the major bioactive components present in propolis, exhibits versatile bioactivities, especially for its potent cytotoxic effects on several cancer cell models. To understand the pharmacokinetic characteristics of CAPE, the binding interaction between CAPE and human serum albumin (HSA) was investigated in vitro using multiple spectroscopic methods and molecular docking. The results reveal that CAPE exhibits a distinctive binding interaction with HSA comparing with other propolis components. The association constant K(A) (L mol(-1)) of the binding reaches 10(6) order of magnitude, which is significantly stronger than the other components of propolis. Based on the theory of fluorescence resonance energy transfer, the binding distance was calculated as 5.7 nm, which is longer than that of the other components of propolis. The thermodynamic results indicate that the binding is mainly driven by hydrogen bonds and van der Waals force. The docking and drugs (warfarin and ibuprofen) competitive results show that CAPE is located in the subdomain IIA (Sudlow's site I, FA7) of HSA, and Gln196 and Lys199 contribute to the hydrogen bonds. Circular dichroism spectra suggest an alteration of the secondary structure of HSA due to its partial unfolding in the presence of CAPE.

Association Between Two CHRNA3 Variants and Susceptibility of Lung Cancer: a Meta-analysis

Scientific Reports. 2016  |  Pubmed ID: 26831765

Genome-wide association studies (GWAS) have identified two CHRNA3 polymorphisms (rs578776 and rs938682) associated with lung cancer risk. Furthermore, these polymorphisms were investigated and genotyped by PCR analysis. All eligible case-control studies published up to Mar 1st 2015 were identified by searching Pubmed and Embase database. Negative association between rs578776-T allele and risk of lung cancer was obtained without obvious heterogeneity (OR: 0.83, 95% CI: 0.79-0.86; p = 0.898 for Q test). Rs938682-C allele carriers had a 12% to 28% decreased risk. Genotype model analysis showed results of dominant model for rs578776 (OR with 95% CI: 0.839(0.718-0.981)), dominant model for rs938682 (OR with 95% CI: 0.778(0.663-0.912)) and homozygous model for rs938682 (OR with 95% CI: 0.767(0.708-0.831)) were statistically significant. Subgroup analysis indicated rs578776-T variant had protective effect in Smokers, Caucasians, two histology subgroups, and two match subgroups. Meanwhile, rs938682-C allele was associated with decreased risk in Smokers, Caucasians, Lung cancer, and two match subgroups. Meta-regression suggested ethnicity might be the major source of heterogeneity in allele model and homozygous model for rs938682. Moreover, smoking status might contribute to part of heterogeneity under allele model. In summary, this meta-analysis suggested both rs578776 and rs938682 were significantly associated with the susceptibility of lung cancer.

Reductions of Left Ventricular Mass and Atrial Size Following Renal Denervation: a Meta-analysis

Clinical Research in Cardiology : Official Journal of the German Cardiac Society. Aug, 2016  |  Pubmed ID: 26838292

Renal denervation (RDN), a novel therapy for resistant hypertension, has been shown to have an effect on cardiac remodeling in several small studies. We aimed to pool currently available data to assess the effects of RDN on left ventricular hypertrophy (LVH) and left atrial (LA) enlargement.

The Developmental Effect of Difenoconazole on Zebrafish Embryos: A Mechanism Research

Environmental Pollution (Barking, Essex : 1987). May, 2016  |  Pubmed ID: 26840512

Difenoconazole is a widely used triazole fungicide and has been reported to have negative impacts on zebrafish embryos. To investigate the mechanism of its developmental toxicity, zebrafish embryos were exposed to 0.5 and 2.0 mg/L difenoconazole for 96 h. The morphological and physiological indicators of embryo development were tested. The total cholesterol (TCHO) level, triglyceride (TG) level and malondialdehyde (MDA) content were measured at 96 hpf (hours post-fertilization). In addition, the transcription of genes related to embryo development, the antioxidant system, lipid synthesis and metabolism was quantified. Our results showed that a large suite of symptoms were induced by difenoconazole, including hatching regression, heart rate decrease, growth inhibition and teratogenic effects. 0.5 mg/L difenoconazole could significantly increase the TG content of zebrafish embryos at 96 hpf, while no apparent change in the TCHO and MDA level was observed post 96 h exposure. Q-PCR (quantitative real-time polymerase chain reaction) results showed that the transcription of genes related to embryonic development was decreased after exposure. Genes related to hatching, retinoic acid metabolism and lipid homeostasis were up-regulated by difenoconazole.

Nanotopographical Modulation of Cell Function Through Nuclear Deformation

ACS Applied Materials & Interfaces. Mar, 2016  |  Pubmed ID: 26844365

Although nanotopography has been shown to be a potent modulator of cell behavior, it is unclear how the nanotopographical cue, through focal adhesions, affects the nucleus, eventually influencing cell phenotype and function. Thus, current methods to apply nanotopography to regulate cell behavior are basically empirical. We, herein, engineered nanotopographies of various shapes (gratings and pillars) and dimensions (feature size, spacing and height), and thoroughly investigated cell spreading, focal adhesion organization and nuclear deformation of human primary fibroblasts as the model cell grown on the nanotopographies. We examined the correlation between nuclear deformation and cell functions such as cell proliferation, transfection and extracellular matrix protein type I collagen production. It was found that the nanoscale gratings and pillars could facilitate focal adhesion elongation by providing anchoring sites, and the nanogratings could orient focal adhesions and nuclei along the nanograting direction, depending on not only the feature size but also the spacing of the nanogratings. Compared with continuous nanogratings, discrete nanopillars tended to disrupt the formation and growth of focal adhesions and thus had less profound effects on nuclear deformation. Notably, nuclear volume could be effectively modulated by the height of nanotopography. Further, we demonstrated that cell proliferation, transfection, and type I collagen production were strongly associated with the nuclear volume, indicating that the nucleus serves as a critical mechanosensor for cell regulation. Our study delineated the relationships between focal adhesions, nucleus and cell function and highlighted that the nanotopography could regulate cell phenotype and function by modulating nuclear deformation. This study provides insight into the rational design of nanotopography for new biomaterials and the cell-substrate interfaces of implants and medical devices.

Electrophilicities and Protein Covalent Binding of Demethylation Metabolites of Colchicine

Chemical Research in Toxicology. Mar, 2016  |  Pubmed ID: 26845511

Colchicine, an alkaloid existing in plants of Liliaceous colchicum, has been widely used in the treatment of gout and familial Mediterranean fever. The administration of colchicine was found to cause liver injury in humans. The mechanisms of colchicine-induced liver toxicity remain unknown. The objectives of this study were to determine the electrophilicities of demethylation metabolites of colchicine and investigate the protein adductions derived from the reactive metabolites of colchicine. Four demethylated colchicine (1-, 2-, 3-, and 10-DMCs), namely, M1-M4, were detected in colchicine-fortified microsomal incubations. Four N-acetyl cysteine (NAC) conjugates (M5-M8) derived from colchicine were detected in the microsomes in the presence of NAC. M5 and M6 were derived from 10-DMC. M7 resulted from the reaction of 2-DMC or 3-DMC with NAC, and M8 originated from 10-DMC. Microsomal protein covalent binding was observed after exposure to colchicine. Two cysteine adducts (CA-1 and CA-2) derived from 10-DMC were found in proteolytically digested microsomal protein samples after incubation with colchicine. The findings allow us to define the chemical property of demethylation metabolites of colchicine and the interaction between protein and the reactive metabolites of colchicine generated in situ.

Demethylation of Tumor Necrosis Factor-α Converting Enzyme Predicts Poor Prognosis in Acute-on-chronic Hepatitis B Liver Failure

Clinics and Research in Hepatology and Gastroenterology. Feb, 2016  |  Pubmed ID: 26850359

Tumor necrosis factor-α converting enzyme (TACE) has been demonstrated to be involved in liver inflammation. However, the significance of TACE methylation in acute-on-chronic hepatitis B liver failure (ACHBLF) has not been demonstrated. This study aims to evaluate TACE methylation status in ACHBLF and determine its predictive value for prognosis.

Longitudinal Contraction Venoplasty in Prevention of Internal Jugular Vein Thrombosis After Free Flap Vascular Anastomosis

Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. Jun, 2016  |  Pubmed ID: 26851318

The vascular anastomosis of free flap with the internal jugular vein stump is susceptible to thrombosis, thus resulting in flap compromise or failure. This study aims to explore the method of longitudinal contraction venoplasty in the prevention of internal jugular vein stump thrombosis after free flap vascular anastomosis and its feasibility.

Inhibition of Na(+)-K(+)-2Cl(-) Cotransporter-1 Attenuates Traumatic Brain Injury-induced Neuronal Apoptosis Via Regulation of Erk Signaling

Neurochemistry International. Mar, 2016  |  Pubmed ID: 26854573

Traumatic brain injury (TBI) is the leading cause of mortality and morbidity worldwide and is characterized by immediate brain damage and secondary injuries, such as brain edema and ischemia. However, the exact pathological mechanisms that comprise these associated secondary injuries have not been fully elucidated. This study aimed to investigate the role of the Na(+)-K(+)-2Cl(-) cotransporter-1 (NKCC1) in the disruption of ion homeostasis and neuronal apoptosis in TBI. Using a traumatic neuron injury (TNI) model in vitro and a controlled cortex injury (CCI) model in vivo, the present study investigated changes in the expression and effects of NKCC1 in TBI using western blot, RNA interference, a lactate dehydrogenase (LDH) release assay, TdT-mediated dUTP Nick end-labeling (TUNEL) analysis, sodium imaging, brain water content, and neurological severity scoring. TBI induced the expression of NKCC1 to be significantly upregulated in the cortex, both in vitro and in vivo. Pharmacological inhibitor bumetanide (Bume) or NKCC1 RNA interference significantly attenuated TBI-induced intracellular Na(+) increase, inhibited neuronal apoptosis, and improved brain edema and neurological function. Furthermore, NKCC1 inhibition also significantly inhibited TBI-induced extracellular signal-regulated kinase (Erk) activation. Erk inhibition significantly protected neurons from TBI injury; however, Erk inhibition had no effect on NKCC1 expression or the neuroprotective effect of NKCC1 inhibition against TBI. This study demonstrates the role of NKCC1 in TBI-induced brain cortex injury, establishing that NKCC1 may play a neurotoxic role in TBI and that the inhibition of NKCC1 may protect neurons from TBI via the regulation of Erk signaling.

Polyphyllin VII Induces Apoptosis in HepG2 Cells Through ROS-mediated Mitochondrial Dysfunction and MAPK Pathways

BMC Complementary and Alternative Medicine. 2016  |  Pubmed ID: 26861252

Paris polyphylla is an oriental folk medicine that has anticancer activities both in vivo and in vitro. Polyphyllin VII (PP7), a pennogenyl saponin from P. polyphylla has been found to exert strong anticancer activity. However, the underlying mechanisms are poorly understood. In the present study, the anticancer effect of polyphyllin VII against human liver cancer cells and the molecular mechanisms were investigated.

A Transient Metabolic Recovery from Early Life Glucose Intolerance in Cystic Fibrosis Ferrets Occurs During Pancreatic Remodeling

Endocrinology. May, 2016  |  Pubmed ID: 26862997

Cystic fibrosis (CF)-related diabetes in humans is intimately related to exocrine pancreatic insufficiency, yet little is known about how these 2 disease processes simultaneously evolve in CF. In this context, we examined CF ferrets during the evolution of exocrine pancreatic disease. At 1 month of age, CF ferrets experienced a glycemic crisis with spontaneous diabetic-level hyperglycemia. This occurred during a spike in pancreatic inflammation that was preceded by pancreatic fibrosis and loss of β-cell mass. Surprisingly, there was spontaneous normalization of glucose levels at 2-3 months, with intermediate hyperglycemia thereafter. Mixed meal tolerance was impaired at all ages, but glucose intolerance was not detected until 4 months. Insulin secretion in response to hyperglycemic clamp and to arginine was impaired. Insulin sensitivity, measured by euglycemic hyperinsulinemic clamp, was normal. Pancreatic inflammation rapidly diminished after 2 months of age during a period where β-cell mass rose and gene expression of islet hormones, peroxisome proliferator-activated receptor-γ, and adiponectin increased. We conclude that active CF exocrine pancreatic inflammation adversely affects β-cells but is followed by islet resurgence. We predict that very young humans with CF may experience a transient glycemic crisis and postulate that pancreatic inflammatory to adipogenic remodeling may facilitate islet adaptation in CF.

Towards a Metropolitan Fundamental Diagram Using Travel Survey Data

PloS One. 2016  |  Pubmed ID: 26866913

Using travel diary data from 2000-2001 and 2010-2012 this research examines fundamental traffic relationships at the metropolitan level. The results of this paper can help to explain the causes of some traffic phenomena. Network average speed by time of day can be explained by trip length and cumulative number of vehicles on the road. A clockwise hysteresis loop is found in the Metropolitan Fundamental Diagram in the morning period and a reverse process happens in the afternoon.

Unique Piezochromic Fluorescence Behavior of Organic Crystal of Carbazole-substituted CNDSB

Chemical Communications (Cambridge, England). Mar, 2016  |  Pubmed ID: 26867660

CzCNDSB with a highly twisted conformation in the solid state is constructed. Single crystal measurements prove that it possesses an inside pore with a diameter of 8 Å and further forms a long-range orderly arrayed channel. CzCNDSB can sense external pressure from 1.0 atm to 9.21 GPa, accompanied by color changes from green to red with excellent reversibility and reproducibility.

Genome-wide Survey of Aux/IAA Gene Family Members in Potato (Solanum Tuberosum): Identification, Expression Analysis, and Evaluation of Their Roles in Tuber Development

Biochemical and Biophysical Research Communications. Mar, 2016  |  Pubmed ID: 26869512

The Auxin/indole-3-acetic acid (Aux/IAA) genes encode short-lived nuclear proteins that are known to be involved in the primary cellular responses to auxin. To date, systematic analysis of the Aux/IAA genes in potato (Solanum tuberosum) has not been conducted. In this study, a total of 26 potato Aux/IAA genes were identified (designated from StIAA1 to StIAA26), and the distribution of four conserved domains shared by the StIAAs were analyzed based on multiple sequence alignment and a motif-based sequence analysis. A phylogenetic analysis of the Aux/IAA gene families of potato and Arabidopsis was also conducted. In order to assess the roles of StIAA genes in tuber development, the results of RNA-seq studies were reformatted to analyze the expression patterns of StIAA genes, and then verified by quantitative real-time PCR. A large number of StIAA genes (12 genes) were highly expressed in stolon organs and in during the tuber initiation and expansion developmental stages, and most of these genes were responsive to indoleacetic acid treatment. Our results suggested that StIAA genes were involved in the process of tuber development and provided insights into functional roles of potato Aux/IAA genes.

Sesquiterpenoids with PTP1B Inhibitory Activity and Cytotoxicity from the Edible Mushroom Pleurotus Citrinopileatus

Planta Medica. May, 2016  |  Pubmed ID: 26872321

One new perhydrobenzannulated 5,5-spiroketal sesquiterpene, pleurospiroketal F (1), as well as six new modified bisabolene sesquiterpenes pleurotins A-F (2-7) were isolated from solid-state fermentation of Pleurotus citrinopileatus. The structures of compounds 1-7 were determined by NMR and MS spectroscopic analysis. The absolute configuration of 1 was determined by X-ray diffraction analysis, while the absolute configurations of 3-7 were assigned using the in situ dimolybdenum circular dichroism method and circular dichroism data comparison. Protein tyrosine phosphatase 1B plays a crucial role as a negative regulator of the insulin-dependent signal cascades. Therefore, the protein tyrosine phosphatase 1B inhibitor can be used for treating type 2 diabetes mellitus and obesity. Compounds 2 and 6 showed moderate inhibitory effects on protein tyrosine phosphatase 1B with IC50 s of 32.1 µM and 30.5 µM, respectively. The kinetic study confirmed compound 2 to be a noncompetitive inhibitor. Compounds 1-7 did not show cytotoxic activity against cancer cell lines (IC50 > 50 µM).

Circular RNA Profile in Gliomas Revealed by Identification Tool UROBORUS

Nucleic Acids Research. May, 2016  |  Pubmed ID: 26873924

Recent evidence suggests that many endogenous circular RNAs (circRNAs) may play roles in biological processes. However, the expression patterns and functions of circRNAs in human diseases are not well understood. Computationally identifying circRNAs from total RNA-seq data is a primary step in studying their expression pattern and biological roles. In this work, we have developed a computational pipeline named UROBORUS to detect circRNAs in total RNA-seq data. By applying UROBORUS to RNA-seq data from 46 gliomas and normal brain samples, we detected thousands of circRNAs supported by at least two read counts, followed by successful experimental validation on 24 circRNAs from the randomly selected 27 circRNAs. UROBORUS is an efficient tool that can detect circRNAs with low expression levels in total RNA-seq without RNase R treatment. The circRNAs expression profiling revealed more than 476 circular RNAs differentially expressed in control brain tissues and gliomas. Together with parental gene expression, we found that circRNA and its parental gene have diversified expression patterns in gliomas and control brain tissues. This study establishes an efficient and sensitive approach for predicting circRNAs using total RNA-seq data. The UROBORUS pipeline can be accessed freely for non-commercial purposes at http://uroborus.openbioinformatics.org/.

Genomic Characterization of Renal Cell Carcinoma with Sarcomatoid Dedifferentiation Pinpoints Recurrent Genomic Alterations

European Urology. Aug, 2016  |  Pubmed ID: 26895810

The genomic features underpinning renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) are not well understood, and at present, there are no specific or effective therapies for sRCC.

Understanding How the Aggregation Structure of Starch Affects Its Gastrointestinal Digestion Rate and Extent

International Journal of Biological Macromolecules. Jun, 2016  |  Pubmed ID: 26899172

Regulating the starch gastrointestinal digestion rate by control of its aggregation structure is an effective way, but the mechanism is still not clear. Multi-scale structure of waxy and normal wheat starches were studied by confocal laser scanning and scanning electron microscopes, as well as wide-angle and small-angle X-ray techniques in this study. In vitro digestion kinetics of those two starches and structure-digestion relationship were also discussed. Both waxy and normal starches show A-type diffraction pattern, but waxy variety shows a slightly higher crystallinity. Small-angle X-ray scattering results show that waxy wheat starch has higher scattering peak intensity (Imax) and a larger crystallinity lamellar repeat distance (Lp) compared with the normal wheat starch. We suggested that the higher digestion rate of waxy starch at initial stage is mainly due to more small-size particles, but the higher crystallinity and the larger crystalline lamellar size limit the digestion extent.

Regarding "Risk Factors for Immediate and Delayed-Onset Fever After Percutaneous Transhepatic Biliary Drainage"

Cardiovascular and Interventional Radiology. May, 2016  |  Pubmed ID: 26902702

Hybrid Wide-band, Low-phase-noise Scheme for Raman Lasers in Atom Interferometry by Integrating an Acousto-optic Modulator and a Feedback Loop

Applied Optics. Feb, 2016  |  Pubmed ID: 26906364

We report a hybrid scheme for phase-coherent Raman lasers with low phase noise in a wide frequency range. In this scheme, a pair of Raman lasers with a frequency difference of 3.04 GHz is generated by the ±1-order diffracted lights of an acousto-optic modulator (1.52 GHz), where a feedback loop is simultaneously applied for suppressing the phase noise. The beat width of the Raman lasers is narrower than 3 Hz. In the low-frequency range, the phase noise of the Raman lasers is suppressed by 35 dB with the feedback. The phase noise is less than -109  dBc/Hz in the high-frequency range. The sensitivity of an atom gyroscope employing the hybrid Raman lasers can be implicitly improved 10 times. Due to the better high-frequency response, the sensitivity is not limited by the durations of Raman pulses. This work is important for improving the performance of atom-interferometer-based measurements.

Cascade Six-level Phase-mask Achromatic Coronagraph

Applied Optics. Feb, 2016  |  Pubmed ID: 26906367

A cascade six-level phase-mask achromatic coronagraph is proposed. We show that, for the ideal aberration-free case, the average suppression of the central starlight in a three-stage six-level phase-mask achromatic coronagraph (SLPMC) can reach about 10⁻⁸ over a 40% bandwidth. We also do the optimization analysis of the working wavelength of each phase mask in the three-stage SLPMC. With optimization, the starlight can be stably suppressed to less than 10⁻⁸ (average about 10⁻¹⁰) over the whole 40% bandwidth.

Impaired Social Cognition in Patients with Interictal Epileptiform Discharges in the Frontal Lobe

Epilepsy & Behavior : E&B. Apr, 2016  |  Pubmed ID: 26921598

Patients with epilepsy frequently experience cognitive impairments, including impairments in social cognition. However, there is a lack of direct examinations of the affective and cognitive aspects of social cognition in such patients. The neural correlates remain to be identified. The present study was designed to examine the degree of impairments in different aspects of social cognition including empathy, emotion recognition, and Theory of Mind (ToM) in patients with epilepsy. In addition, we further explored factors related to the impairments, highlighting the specific importance of the frontal region.

[Effects of Inhaled Short-acting Bronchodilators on Diaphragm Function and Neural Respiratory Drive During Maximal Isocapnic Ventilation in Patients with Chronic Obstructive Pulmonary Disease]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Feb, 2016  |  Pubmed ID: 26922022

To investigate the effects of inhaled short-acting bronchodilators on diaphragm function and neural respiratory drive in patients with chronic obstructive pulmonary disease (COPD) during maximal isocapnic ventilation (MIV).

Discovery of Potent and Orally Active Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitors As a Potential Therapy for Diabetic Macular Edema

Journal of Medicinal Chemistry. Mar, 2016  |  Pubmed ID: 26927682

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered to be a promising therapeutic target for several inflammation-associated diseases. Herein, we describe the discovery of a series of pyrimidone derivatives as Lp-PLA2 inhibitors. Systematic structural modifications led to the identification of several pyrimidone compounds with promising in vitro inhibitory potency and pharmacokinetic properties. Compound 14c, selected for in vivo evaluation, demonstrated decent pharmacokinetic profiles and robust inhibitory potency against Lp-PLA2 in Sprague-Dawley (SD) rats. Furthermore, 14c significantly inhibited retinal thickening in STZ-induced diabetic SD rats as a model of diabetic macular edema (DME) after oral dosing for 4 weeks. Taken together, these results suggested that 14c can serve as a valuable lead in the search for new Lp-PLA2 inhibitors for prevention and/or treatment of DME.

Comprehensive Genomic Profiling Identifies Frequent Drug-Sensitive EGFR Exon 19 Deletions in NSCLC Not Identified by Prior Molecular Testing

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Jul, 2016  |  Pubmed ID: 26933124

Reliable detection of drug-sensitive activating EGFR mutations is critical in the care of advanced non-small cell lung cancer (NSCLC), but such testing is commonly performed using a wide variety of platforms, many of which lack rigorous analytic validation.

Oncogenic ALK Fusion in Rare and Aggressive Subtype of Colorectal Adenocarcinoma As a Potential Therapeutic Target

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Aug, 2016  |  Pubmed ID: 26933125

Chromosomal translocations in the anaplastic lymphoma kinase (ALK) gene have been identified as oncogenic drivers in lung adenocarcinomas and other tumors, recently including rare cases of colorectal carcinoma. We identified a patient with refractory metastatic colorectal carcinoma harboring a STRN-ALK gene fusion who achieved an exceptional clinical benefit to the ALK inhibitor ceritinib. Our goal was to further define the clinicopathologic features of ALK-rearranged colorectal carcinoma in a large cohort.

4C-seq Revealed Long-range Interactions of a Functional Enhancer at the 8q24 Prostate Cancer Risk Locus

Scientific Reports. 2016  |  Pubmed ID: 26934861

Genome-wide association studies (GWAS) have identified >100 independent susceptibility loci for prostate cancer, including the hot spot at 8q24. However, how genetic variants at this locus confer disease risk hasn't been fully characterized. Using circularized chromosome conformation capture (4C) coupled with next-generation sequencing and an enhancer at 8q24 as "bait", we identified genome-wide partners interacting with this enhancer in cell lines LNCaP and C4-2B. These 4C-identified regions are distributed in open nuclear compartments, featuring active histone marks (H3K4me1, H3K4me2 and H3K27Ac). Transcription factors NKX3-1, FOXA1 and AR (androgen receptor) tend to occupy these 4C regions. We identified genes located at the interacting regions, and found them linked to positive regulation of mesenchymal cell proliferation in LNCaP and C4-2B, and several pathways (TGF beta signaling pathway in LNCaP and p53 pathway in C4-2B). Common genes (e.g. MYC and POU5F1B) were identified in both prostate cancer cell lines. However, each cell line also had exclusive genes (e.g. ELAC2 and PTEN in LNCaP and BRCA2 and ZFHX3 in C4-2B). In addition, BCL-2 identified in C4-2B might contribute to the progression of androgen-refractory prostate cancer. Overall, our work reveals key genes and pathways involved in prostate cancer onset and progression.

Photochemical Fabrication of 3D Hierarchical Mn3O4/H-TiO2 Composite Films with Excellent Electrochemical Capacitance Performance

Physical Chemistry Chemical Physics : PCCP. Mar, 2016  |  Pubmed ID: 26939614

We herein report a novel, energy-saving and environmentally benign photodeposition approach to fabricate a manganese oxide film on hydrogenated TiO2 (H-TiO2) nanotube arrays using a Mn(2+)-containing solution as a precursor. Mn(2+) ions are oxidized to Mn3O4 by the photogenerated holes during the photodeposition. The preferential growth of Mn3O4 on the nucleation sites leads to the formation of Mn3O4 nanorods on each H-TiO2 nanotube, forming a 3D hierarchical Mn3O4/H-TiO2 composite film. The as-fabricated 3D hierarchical Mn3O4/H-TiO2 composite film electrode delivers a high specific capacitance of 508 F g(-1) at a current of 0.7 A g(-1). The composite film electrode still shows a specific capacitance of 228 F g(-1) even at a high rate of 35.7 A g(-1), demonstrating its prominent rate capability. Remarkably, the composite film electrode shows no obvious capacitance decay after 10,000 charge/discharge cycles at a current density of 3.6 A g(-1), revealing its superior electrochemical cycling stability. The prominent pseudocapacitive performance of the composite film electrode can be attributed to its unique structure characteristics. The as-constructed energy-saving and environmentally benign photodeposition method can be used as a general and efficient route to prepare other composite materials with controlled morphologies and dimensions.

Alkaline Ceramidase 2 and Its Bioactive Product Sphingosine Are Novel Regulators of the DNA Damage Response

Oncotarget. Apr, 2016  |  Pubmed ID: 26943039

Human cells respond to DNA damage by elevating sphingosine, a bioactive sphingolipid that induces programmed cell death (PCD) in response to various forms of stress, but its regulation and role in the DNA damage response remain obscure. Herein we demonstrate that DNA damage increases sphingosine levels in tumor cells by upregulating alkaline ceramidase 2 (ACER2) and that the upregulation of the ACER2/sphingosine pathway induces PCD in response to DNA damage by increasing the production of reactive oxygen species (ROS). Treatment with the DNA damaging agent doxorubicin increased both ACER2 expression and sphingosine levels in HCT116 cells in a dose-dependent manner. ACER2 overexpression increased sphingosine in HeLa cells whereas knocking down ACER2 inhibited the doxorubicin-induced increase in sphingosine in HCT116 cells, suggesting that DNA damage elevates sphingosine by upregulating ACER2. Knocking down ACER2 inhibited an increase in the apoptotic and necrotic cell population and the cleavage of poly ADP ribose polymerase (PARP) in HCT116 cells in response to doxorubicin as well as doxorubicin-induced release of lactate dehydrogenase (LDH) from these cells. Similar to treatment with doxorubicin, ACER2 overexpression induced an increase in the apoptotic and necrotic cell population and PARP cleavage in HeLa cells and LDH release from cells, suggesting that ACER2 upregulation mediates PCD in response to DNA damage through sphingosine. Mechanistic studies demonstrated that the upregulation of the ACER2/sphingosine pathway induces PCD by increasing ROS levels. Taken together, these results suggest that the ACER2/sphingosine pathway mediates PCD in response to DNA damage through ROS production.

OSKM Induce Extraembryonic Endoderm Stem Cells in Parallel to Induced Pluripotent Stem Cells

Stem Cell Reports. Apr, 2016  |  Pubmed ID: 26947975

The reprogramming factors OCT4, SOX2, KLF4, and MYC (OSKM) can reactivate the pluripotency network in terminally differentiated cells, but also regulate expression of non-pluripotency genes in other contexts, such as the mouse primitive endoderm. The primitive endoderm is an extraembryonic lineage established in parallel to the pluripotent epiblast in the blastocyst, and is the progenitor pool for extraembryonic endoderm stem (XEN) cells. We show that OSKM induce expression of endodermal genes, leading to formation of induced XEN (iXEN) cells, which possess key properties of blastocyst-derived XEN cells, including morphology, transcription profile, self-renewal, and multipotency. Our data show that iXEN cells arise in parallel to induced pluripotent stem cells, indicating that OSKM drive cells to two distinct cell fates during reprogramming.

Effects of Human Umbilical Cord Mesenchymal Stem Cells on Human Trophoblast Cell Functions In Vitro

Stem Cells International. 2016  |  Pubmed ID: 26949402

Trophoblast cell dysfunction is involved in many disorders during pregnancy such as preeclampsia and intrauterine growth restriction. Few treatments exist, however, that target improving trophoblast cell function. Human umbilical cord mesenchymal stem cells (hUCMSCs) are capable of self-renewing, can undergo multilineage differentiation, and have homing abilities; in addition, they have immunomodulatory effects and paracrine properties and thus are a prospective source for cell therapy. To identify whether hUCMSCs can regulate trophoblast cell functions, we treated trophoblast cells with hUCMSC supernatant or cocultured them with hUCMSCs. Both treatments remarkably enhanced the migration and invasion abilities of trophoblast cells and upregulated their proliferation ability. At a certain concentration, hUCMSCs also modulated hCG, PIGF, and sEndoglin levels in the trophoblast culture medium. Thus, hUCMSCs have a positive effect on trophoblast cellular functions, which may provide a new avenue for treatment of placenta-related diseases during pregnancy.

The Utility of Diaton Tonometer Measurements in Patients With Ocular Hypertension, Glaucoma, and Glaucoma Tube Shunts: A Preliminary Study for Its Potential Use in Keratoprosthesis Patients

Journal of Glaucoma. Aug, 2016  |  Pubmed ID: 26950582

Glaucoma is common in patients with the Boston type 1 keratoprosthesis (KPro). Because of the inability to perform corneal applanation in KPro patients, digital palpation is currently the mainstay for assessment of intraocular pressure (IOP). The purpose of this study was to determine whether the Diaton tonometer, which estimates IOP through transpalpebral scleral indentation, can reasonably detect high IOP when compared with Goldmann applanation tonometry (GAT) in patients with ocular hypertension, glaucoma, or glaucoma tube shunts. If reliable in these patients, it may be helpful in patients with KPros.

Targeting Rad50 Sensitizes Human Nasopharyngeal Carcinoma Cells to Radiotherapy

BMC Cancer. 2016  |  Pubmed ID: 26951044

The Mre11-Rad50-Nbs1 (MRN) complex is well known for its crucial role in initiating DNA double strand breaks (DSBs) repair pathways to resistant irradiation (IR) injury and thus facilitating radioresistance which severely reduces radiocurability of nasopharyngeal cancer (NPC). Targeting native cellular MRN function would sensitize NPC cells to IR.

The Oryza Sativa Regulator HDR1 Associates with the Kinase OsK4 to Control Photoperiodic Flowering

PLoS Genetics. Mar, 2016  |  Pubmed ID: 26954091

Rice is a facultative short-day plant (SDP), and the regulatory pathways for flowering time are conserved, but functionally modified, in Arabidopsis and rice. Heading date 1 (Hd1), an ortholog of Arabidopsis CONSTANS (CO), is a key regulator that suppresses flowering under long-day conditions (LDs), but promotes flowering under short-day conditions (SDs) by influencing the expression of the florigen gene Heading date 3a (Hd3a). Another key regulator, Early heading date 1 (Ehd1), is an evolutionarily unique gene with no orthologs in Arabidopsis, which acts as a flowering activator under both SD and LD by promoting the rice florigen genes Hd3a and RICE FLOWERING LOCUST 1 (RFT1). Here, we report the isolation and characterization of the flowering regulator Heading Date Repressor1 (HDR1) in rice. The hdr1 mutant exhibits an early flowering phenotype under natural LD in a paddy field in Beijing, China (39°54'N, 116°23'E), as well as under LD but not SD in a growth chamber, indicating that HDR1 may functionally regulate flowering time via the photoperiod-dependent pathway. HDR1 encodes a nuclear protein that is most active in leaves and floral organs and exhibits a typical diurnal expression pattern. We determined that HDR1 is a novel suppressor of flowering that upregulates Hd1 and downregulates Ehd1, leading to the downregulation of Hd3a and RFT1 under LDs. We have further identified an HDR1-interacting kinase, OsK4, another suppressor of rice flowering under LDs. OsK4 acts similarly to HDR1, suppressing flowering by upregulating Hd1 and downregulating Ehd1 under LDs, and OsK4 can phosphorylate HD1 with HDR1 presents. These results collectively reveal the transcriptional regulators of Hd1 for the day-length-dependent control of flowering time in rice.

Protection of Bovine Mammary Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Cell Damage by Resveratrol

Oxidative Medicine and Cellular Longevity. 2016  |  Pubmed ID: 26962394

The mammary epithelial cells (MECs) of high-producing dairy cows are likely to be subject to oxidative stress (OS) due to the intensive cell metabolism. The objectives of this study were to investigate the cytoprotective effects of resveratrol against hydrogen peroxide- (H2O2-) induced OS in cultured bovine MECs (MAC-T). Pretreatment of MAC-T cells with resveratrol could rescue the decrease in cell viability and resulted in lower intracellular reactive oxygen species (ROS) accumulation after H2O2 exposure. Resveratrol helped MAC-T cells to prevent H2O2-induced endoplasmic reticulum stress and mitochondria-related cell apoptosis. Moreover, resveratrol induced mRNA expression of multiple antioxidant defense genes in MAC-T cells under normal/oxidative conditions. Nuclear factor erythroid 2-related factor 2 (Nrf2) was required for the cytoprotective effects on MAC-T cells by resveratrol, as knockdown of Nrf2 significantly abolished resveratrol-induced cytoprotective effects against OS. In addition, by using selective inhibitors, we further confirmed that the induction of Nrf2 by resveratrol was mediated through the prolonged activation of PI3K/Akt and ERK/MAPK pathways but negatively regulated by p38/MAPK pathway. Overall, resveratrol has beneficial effects on bovine MECs redox balance and may be potentially used as a therapeutic medicine against oxidative insult in lactating animals.

A Comparative Assessment of the Influences of Human Impacts on Soil Cd Concentrations Based on Stepwise Linear Regression, Classification and Regression Tree, and Random Forest Models

PloS One. 2016  |  Pubmed ID: 26964095

Soil cadmium (Cd) contamination has attracted a great deal of attention because of its detrimental effects on animals and humans. This study aimed to develop and compare the performances of stepwise linear regression (SLR), classification and regression tree (CART) and random forest (RF) models in the prediction and mapping of the spatial distribution of soil Cd and to identify likely sources of Cd accumulation in Fuyang County, eastern China. Soil Cd data from 276 topsoil (0-20 cm) samples were collected and randomly divided into calibration (222 samples) and validation datasets (54 samples). Auxiliary data, including detailed land use information, soil organic matter, soil pH, and topographic data, were incorporated into the models to simulate the soil Cd concentrations and further identify the main factors influencing soil Cd variation. The predictive models for soil Cd concentration exhibited acceptable overall accuracies (72.22% for SLR, 70.37% for CART, and 75.93% for RF). The SLR model exhibited the largest predicted deviation, with a mean error (ME) of 0.074 mg/kg, a mean absolute error (MAE) of 0.160 mg/kg, and a root mean squared error (RMSE) of 0.274 mg/kg, and the RF model produced the results closest to the observed values, with an ME of 0.002 mg/kg, an MAE of 0.132 mg/kg, and an RMSE of 0.198 mg/kg. The RF model also exhibited the greatest R2 value (0.772). The CART model predictions closely followed, with ME, MAE, RMSE, and R2 values of 0.013 mg/kg, 0.154 mg/kg, 0.230 mg/kg and 0.644, respectively. The three prediction maps generally exhibited similar and realistic spatial patterns of soil Cd contamination. The heavily Cd-affected areas were primarily located in the alluvial valley plain of the Fuchun River and its tributaries because of the dramatic industrialization and urbanization processes that have occurred there. The most important variable for explaining high levels of soil Cd accumulation was the presence of metal smelting industries. The good performance of the RF model was attributable to its ability to handle the non-linear and hierarchical relationships between soil Cd and environmental variables. These results confirm that the RF approach is promising for the prediction and spatial distribution mapping of soil Cd at the regional scale.

Integrated Genomic DNA/RNA Profiling of Hematologic Malignancies in the Clinical Setting

Blood. Jun, 2016  |  Pubmed ID: 26966091

The spectrum of somatic alterations in hematologic malignancies includes substitutions, insertions/deletions (indels), copy number alterations (CNAs), and a wide range of gene fusions; no current clinically available single assay captures the different types of alterations. We developed a novel next-generation sequencing-based assay to identify all classes of genomic alterations using archived formalin-fixed paraffin-embedded blood and bone marrow samples with high accuracy in a clinically relevant time frame, which is performed in our Clinical Laboratory Improvement Amendments-certified College of American Pathologists-accredited laboratory. Targeted capture of DNA/RNA and next-generation sequencing reliably identifies substitutions, indels, CNAs, and gene fusions, with similar accuracy to lower-throughput assays that focus on specific genes and types of genomic alterations. Profiling of 3696 samples identified recurrent somatic alterations that impact diagnosis, prognosis, and therapy selection. This comprehensive genomic profiling approach has proved effective in detecting all types of genomic alterations, including fusion transcripts, which increases the ability to identify clinically relevant genomic alterations with therapeutic relevance.

Configurational Space Discretization and Free Energy Calculation in Complex Molecular Systems

Scientific Reports. 2016  |  Pubmed ID: 26974524

We sought to design a free energy calculation scheme with the hope of saving cost for generating dynamical information that is inherent in trajectories. We demonstrated that snapshots in a converged trajectory set are associated with implicit conformers that have invariant statistical weight distribution (ISWD). Since infinite number of sets of implicit conformers with ISWD may be created through independent converged trajectory sets, we hypothesized that explicit conformers with ISWD may be constructed for complex molecular systems through systematic increase of conformer fineness, and tested the hypothesis in lipid molecule palmitoyloleoylphosphatidylcholine (POPC). Furthermore, when explicit conformers with ISWD were utilized as basic states to define conformational entropy, change of which between two given macrostates was found to be equivalent to change of free energy except a mere difference of a negative temperature factor, and change of enthalpy essentially cancels corresponding change of average intra-conformer entropy. By implicitly taking advantage of entropy enthalpy compensation and forgoing all dynamical information, constructing explicit conformers with ISWD and counting thermally accessible number of which for interested end macrostates is likely to be an efficient and reliable alternative end point free energy calculation strategy.

Mass-Transfer-Controlled Dynamic Interfacial Tension in Microfluidic Emulsification Processes

Langmuir : the ACS Journal of Surfaces and Colloids. Apr, 2016  |  Pubmed ID: 26978599

Varied interfacial tension caused by the unsaturated adsorption of surfactants on dripping droplet surfaces is experimentally studied. The mass transfer and adsorption of surfactants, as well as the generation of fresh interfaces, are considered the main factors dominating the surfactant adsorption ratio on droplet surfaces. The diffusion and convective mass transfer of the surfactants are first distinguished by comparing the adsorption depth and the mass flux boundary layer thickness. A characterized mass transfer time is then calculated by introducing an effective diffusion coefficient. A time ratio is furthermore defined by dividing the droplet generation time by the characteristic mass transfer time, t/tm, in order to compare the rates of surfactant mass transfer and droplet generation. Different control mechanisms for different surfactants are analyzed based on the range of t/t(m), and a criterion time ratio using a simplified characteristic mass transfer time, t(m)*, is finally proposed for predicting the appearance of dynamic interfacial tension.

Aspiration Thrombectomy Using a Large-size Catheter for Acute Lower Extremity Deep Vein Thrombosis

Journal of Vascular Surgery. Venous and Lymphatic Disorders. Apr, 2016  |  Pubmed ID: 26993862

This study retrospectively evaluated the safety and efficacy of aspiration thrombectomy using a large-size catheter for acute lower extremity deep vein thrombosis (DVT).

Selective Impairment of Attention Networks During Propofol Anesthesia After Gynecological Surgery in Middle-aged Women

Journal of the Neurological Sciences. Apr, 2016  |  Pubmed ID: 27000237

Postoperative cognitive dysfunction is a common complication of anesthesia and surgery. Attention networks are essential components of cognitive function and are subject to impairment after anesthesia and surgery. It is not known whether such impairment represents a global attention deficit or relates to a specific attention network. We used an Attention Network Task (ANT) to examine the efficiency of the alerting, orienting, and executive control attention networks in middle-aged women (40-60 years) undergoing gynecologic surgery. A matched group of medical inpatients were recruited as a control.

Variants in CXCR4 Associate with Juvenile Idiopathic Arthritis Susceptibility

BMC Medical Genetics. 2016  |  Pubmed ID: 27005825

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease among children, the etiology of which involves a strong genetic component, but much of the underlying genetic determinants still remain unknown. Our aim was to identify novel genetic variants that predispose to JIA.

Aging-related Elevation of Sphingoid Bases Shortens Yeast Chronological Life Span by Compromising Mitochondrial Function

Oncotarget. Apr, 2016  |  Pubmed ID: 27008706

Sphingoid bases (SBs) as bioactive sphingolipids, have been implicated in aging in yeast. However, we know neither how SBs are regulated during yeast aging nor how they, in turn, regulate it. Herein, we demonstrate that the yeast alkaline ceramidases (YPC1 and YDC1) and SB kinases (LCB4 and LCB5) cooperate in regulating SBs during the aging process and that SBs shortens chronological life span (CLS) by compromising mitochondrial functions. With a lipidomics approach, we found that SBs were increased in a time-dependent manner during yeast aging. We also demonstrated that among the enzymes known for being responsible for the metabolism of SBs, YPC1 was upregulated whereas LCB4/5 were downregulated in the course of aging. This inverse regulation of YPC1 and LCB4/5 led to the aging-related upregulation of SBs in yeast and a reduction in CLS. With the proteomics-based approach (SILAC), we revealed that increased SBs altered the levels of proteins related to mitochondria. Further mechanistic studies demonstrated that increased SBs inhibited mitochondrial fusion and caused fragmentation, resulting in decreases in mtDNA copy numbers, ATP levels, mitochondrial membrane potentials, and oxygen consumption. Taken together, these results suggest that increased SBs mediate the aging process by impairing mitochondrial structural integrity and functions.

[Investigation on the Role on Perindopril for Prevention and Treatment of Glucocorticoid-induced Osteoporosis in Rabbits]

Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology. Jan, 2016  |  Pubmed ID: 27019898

To investigate the role of perindopril for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) in rabbits.

Theoretical Study on Free Fatty Acid Elimination Mechanism for Waste Cooking Oils to Biodiesel over Acid Catalyst

Journal of Molecular Graphics & Modelling. May, 2016  |  Pubmed ID: 27023919

A theoretical investigation on the esterification mechanism of free fatty acid (FFA) in waste cooking oils (WCOs) has been carried out using DMol(3) module based on the density functional theory (DFT). Three potential pathways of FFA esterification reaction are designed to achieve the formation of fatty acid methyl ester (FAME), and calculated results show that the energy barrier can be efficiently reduced from 88.597kcal/mol to 15.318kcal/mol by acid catalyst. The molar enthalpy changes (ΔrHm°) of designed pathways are negative, indicating that FFA esterification reaction is an exothermic process. The obtained favorable energy pathway is: H(+) firstly activates FFA, then the intermediate combines with methanol to form a tetrahedral structure, and finally, producing FAME after removing a water molecule. The rate-determining step is the combination of the activated FFA with methanol, and the activation energy is about 11.513kcal/mol at 298.15K. Our results should provide basic and reliable theoretical data for further understanding the elimination mechanism of FFA over acid catalyst in the conversion of WCOs to biodiesel products.

The Enhanced Recovery After Surgery (ERAS) Program in Liver Surgery: a Meta-analysis of Randomized Controlled Trials

SpringerPlus. 2016  |  Pubmed ID: 27026903

The enhanced recovery after surgery (ERAS) program aims to attenuate the surgical stress response and decrease postoperative complications. It has increasingly replaced conventional approaches in surgical care. To evaluate the benefits and harms of the ERAS program compared to conventional care in patients undergoing liver surgery. We searched the MEDLINE, PubMed, EMBASE and Cochrane databases. All RCTs that compared the ERAS program with conventional care were selected. Four RCTs were eligible for analysis, which included 634 patients (309 ERAS vs. 325 conventional). Overall morbidity (RR 0.67; 95 % CI 0.48-0.92; p = 0.01), primary length of stay (WMD -2.71; 95 % CI -3.43 to -1.99; p < 0.00001), total length of stay (WMD -2.10; 95 % CI -3.96 to -0.24; p = 0.03), time of functional recovery (WMD -2.30; 95 % CI -3.77 to -0.83; p = 0.002), and time to first flatus (SMD, -0.52; 95 % CI -0.69 to -0.35; p < 0.00001) were significantly shortened in the ERAS group. Quality of life was also better in the ERAS group. However, no significant differences were noted in mortality, readmission rates, operative time and intraoperative blood loss. The ERAS Program for liver surgery significantly reduced overall morbidity rates, accelerated functional recovery, and shortened the primary and total hospital stay without compromising readmission rates. Therefore, ERAS appears to be safe and effective. However, the conclusions are limited because of the low methodological quality of the analyzed studies. Further studies are needed to provide more solid evidence.

Comparison of the Type and Severity of Early Attentional Network Decline After Total Intravenous or Epidural Anesthesia in Middle-aged Women After Gynecological Surgery

International Clinical Psychopharmacology. Sep, 2016  |  Pubmed ID: 27028371

Compared with regional anesthesia, general anesthesia may increase the risk of postoperative cognitive decline. This study aimed to investigate the type and severity of attentional network decline and the recovery of attentional networks in middle-aged women after gynecological surgery. A total of 140 consenting women undergoing elective gynecological surgery were enrolled in the study. Patients were assigned randomly to receive either total intravenous anesthesia or epidural anesthesia. To determine the efficacy of the attentional networks, patients were examined for alerting, orienting, and executive networks on the preoperative day and on the first and fifth postoperative days using the attentional network test. Significant differences were observed in the effect scores of the three attentional networks at all time points. These effect scores differed significantly between groups and between 1 and 5 days postoperation (DPO). Participants showed significantly lower effect scores for the alerting and orienting network tasks and had more difficulties in resolving conflict at 1 DPO compared with the baseline. On comparing effect scores between baseline and 5 DPO, no significant differences on the alerting and orienting network tasks were observed in the epidural anesthesia group, a significant difference on the orienting network task was observed in the general anesthesia group, and significant differences on the executive control network were observed in both the groups. Compared with epidural anesthesia, total intravenous anesthesia is more likely to impair and delay the recovery of attentional networks in middle-aged women undergoing elective hysterectomy. The executive control function showed marked damage and there were difficulties in recovery from either type of anesthesia.

[Cervical Esophagostomy Improves the Life Quality of Patients with Dysphagia Induced by Radiotherapy for Nasopharyngeal Carcinoma]

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Chinese Journal of Otorhinolaryngology Head and Neck Surgery. Mar, 2016  |  Pubmed ID: 27033571

To evaluate the effect of cervical esophagostomy for the treatment of patients with dysphagia induced by radiotherapy, in order to improve the therapeutic effects.

Free Perforating Branch Flap for Primary Repairing the Huge Soft-tissue Defects on the Scalp and Face

The Journal of Dermatological Treatment. Apr, 2016  |  Pubmed ID: 27044910

This study aimed to explore the effect of free perforating branch flap on the reconstruction of huge soft-tissue defects on the scalp and face.

Antioxidant Activities and Molecular Mechanisms of the Ethanol Extracts of Baccharis Propolis and Eucalyptus Propolis in RAW64.7 Cells

Pharmaceutical Biology. Oct, 2016  |  Pubmed ID: 27049854

Context Numerous studies have reported that propolis possesses strong antioxidant activities. However, their antioxidant molecular mechanisms are unclear. Objective We utilize ethanol extracts of Chinese propolis (EECP) as a reference to compare ethanol extracts of Eucalyptus propolis (EEEP) with ethanol extracts of Baccharis propolis (EEBGP) based on their antioxidant capacities and underlying molecular mechanisms. Materials and methods HPLC and chemical analysis are utilized to evaluate compositions and antioxidant activities. ROS-eliminating effects of EEBGP (20-75 μg/mL), EEEP (1.25-3.75 μg/mL) and EECP (1.25-5 μg/mL) are also determined by flow cytometry analysis. Moreover, we compared antioxidant capacities by determining their effects on expressions of antioxidant genes in RAW264.7 cells with qRT-PCR, western blot and confocal microscopy analysis. Results EEBGP mainly contains chlorogenic acid (8.98 ± 0.86 mg/g), kaempferide (11.18 ± 8.31 mg/g) and artepillin C (107.70 ± 10.86 mg/g), but EEEP contains 10 compositions, whereas EECP contains 17 compositions. Meantime, although EEEP shows DPPH (IC50 19.55 ± 1.28), ABTS (IC50 20.0 ± 0.31) and reducing power (2.70 ± 0.08 mmol TE/g) better than EEBGP's DPPH (IC50 43.85 ± 0.54), ABTS (IC50 38.2 ± 0.33) and reducing power (1.53 ± 0.05 mmol TE/g), EEBGP exerts much higher ROS inhibition rate (40%) than EEEP (under 20%). Moreover, EEBGP strengthen antioxidant system by activating p38/p-p38 and Erk/p-Erk kinase via accelerating nucleus translocation of Nrf2. EEEP and EECP improve antioxidant gene expression only via Erk/p-Erk kinase-Nrf2 signalling pathway. Discussion and conclusion EEBGP and EEEP exert antioxidant activities via different molecular mechanisms, which may depend on chemical compositions.

Lower Bounds on Paraclique Density

Discrete Applied Mathematics (Amsterdam, Netherlands : 1988). May, 2016  |  Pubmed ID: 27057077

The scientific literature teems with clique-centric clustering strategies. In this paper we analyze one such method, the paraclique algorithm. Paraclique has found practical utility in a variety of application domains, and has been successfully employed to reduce the effects of noise. Nevertheless, its formal analysis and worst-case guarantees have remained elusive. We address this issue by deriving a series of lower bounds on paraclique densities.

Proportions and Risk Factors of Developing Multidrug Resistance Among Patients with Tuberculosis in China: A Population-Based Case-Control Study

Microbial Drug Resistance (Larchmont, N.Y.). Apr, 2016  |  Pubmed ID: 27058017

Limited studies have been conducted to explore risk factors of developing multidrug-resistant tuberculosis (MDR-TB) in China. This study aimed to find the proportions and risk factors of developing MDR-TB in China among new patients and previously treated tuberculosis (TB) patients.

[Clinical Analysis of 35 Flap Crisis in Anterolateral Thigh Free Flaps]

Shanghai Kou Qiang Yi Xue = Shanghai Journal of Stomatology. Feb, 2016  |  Pubmed ID: 27063322

PURPOSE:The aim of this study was to analyze the causes of anterolateral thigh (ALT) free flap compromise and improve the success rate of ALT.

The Complete Mitochondrial Genome of the Atylotus Miser (Diptera: Tabanomorpha: Tabanidae), with Mitochondrial Genome Phylogeny of Lower Brachycera (Orthorrhapha)

Gene. Jul, 2016  |  Pubmed ID: 27063560

Brachycera is a clade with over 80,000 described species and originated from the Mesozoic, and its larvae employ comprehensive feeding strategies. The phylogeny of the lower Brachycera has been studied intensively over the past decades. In order to supplement the lack of genetic data in this important group, we sequenced the complete mitochondrial (mt) genome of Atylotus miser as well as the nearly complete mt genomes of another 11 orthorrhaphous flies. The mt genome of A. miser is 15,858bp, which is typical of Diptera, with 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and a 993bp control region. The rest of the orthorrhaphous mt genomes in our study have the similar structure with A. miser. Additionally, we conducted a phylogenetic analysis of 20 mt genomes using Maximum-likelihood and Bayesian methods in order to reconstruct the evolutionary relationship of Orthorrhapha. The results show that all infraorders of Brachycera are monophyletic, and a relationship of Tabanomorpha+((Xylophagomorpha+Stratiomyomorpha)+Muscomorpha) has been proposed. Within Xylophagomorpha, Nemestrinoidae forms the sister group of Xylophagidae.

Genomic Alterations Observed in Colitis-Associated Cancers Are Distinct From Those Found in Sporadic Colorectal Cancers and Vary by Type of Inflammatory Bowel Disease

Gastroenterology. Aug, 2016  |  Pubmed ID: 27063727

Patients with inflammatory bowel diseases, such as Crohn's disease (CD) and ulcerative colitis (UC), are at increased risk for small bowel or colorectal cancers (colitis-associated cancers [CACs]). We compared the spectrum of genomic alterations in CACs with those of sporadic colorectal cancers (CRCs) and investigated differences between CACs from patients with CD vs UC.

Regarding "Endovascular Management of Acute Embolic Occlusion of the Superior Mesenteric Artery: A 12-Year Single-Centre Experience"

Cardiovascular and Interventional Radiology. Jul, 2016  |  Pubmed ID: 27071657

Precise Phase Retrieval Under Harsh Conditions by Constructing New Connected Interferograms

Scientific Reports. 2016  |  Pubmed ID: 27074821

To date, no phase-shifting method can accurately retrieve the phase map from a small set of noisy interferograms with low phase-shifts. In this Letter, we develop a novel approach to resolve this limitation under such harsh conditions. The proposed new method is based on constructing a set of connected interferograms by means of simple subtraction and addition operations, in which all the subset of interferograms have the same phase-shift interval of π/2. According to this characteristic, this set of connected interferograms can be processed with conventional phase retrieval methods as PCA or AIA obtaining accurate results. The reduction in the RMS errors after using our method reaches as high as 93.7% and 89.3% respectively comparing with conventional PCA and AIA methods under harsh conditions. Both simulation and experiment results demonstrate that the new proposed method provides an effective way, with high precision and robustness against noise, for phase retrieval.

Triple-negative Breast Cancers with Amplification of JAK2 at the 9p24 Locus Demonstrate JAK2-specific Dependence

Science Translational Medicine. Apr, 2016  |  Pubmed ID: 27075627

Amplifications at 9p24 have been identified in breast cancer and other malignancies, but the genes within this locus causally associated with oncogenicity or tumor progression remain unclear. Targeted next-generation sequencing of postchemotherapy triple-negative breast cancers (TNBCs) identified a group of 9p24-amplified tumors, which contained focal amplification of the Janus kinase 2 (JAK2) gene. These patients had markedly inferior recurrence-free and overall survival compared to patients with TNBC without JAK2 amplification. Detection of JAK2/9p24 amplifications was more common in chemotherapy-treated TNBCs than in untreated TNBCs or basal-like cancers, or in other breast cancer subtypes. Similar rates of JAK2 amplification were confirmed in patient-derived TNBC xenografts. In patients for whom longitudinal specimens were available, JAK2 amplification was selected for during neoadjuvant chemotherapy and eventual metastatic spread, suggesting a role in tumorigenicity and chemoresistance, phenotypes often attributed to a cancer stem cell-like cell population. In TNBC cell lines with JAK2 copy gains or amplification, specific inhibition of JAK2 signaling reduced mammosphere formation and cooperated with chemotherapy in reducing tumor growth in vivo. In these cells, inhibition of JAK1-signal transducer and activator of transcription 3 (STAT3) signaling had little effect or, in some cases, counteracted JAK2-specific inhibition. Collectively, these results suggest that JAK2-specific inhibitors are more efficacious than dual JAK1/2 inhibitors against JAK2-amplified TNBCs. Furthermore, JAK2 amplification is a potential biomarker for JAK2 dependence, which, in turn, can be used to select patients for clinical trials with JAK2 inhibitors.

Measuring the Aharonov-Anandan Phase in Multiport Photonic Systems

Optics Letters. Apr, 2016  |  Pubmed ID: 27082371

Beyond the adiabatic limit, the Aharonov-Anandan phase is a generalized description of Berry's phase. In this regime, systems with time-independent Hamiltonians may also acquire observable geometric phases. Here we report on a measurement of the Aharonov-Anandan phase in photonics. Different from previous optical experiments on geometric phases, the implementation is based on light modes confined in evanescently coupled waveguides rather than polarization-like systems, thereby physical models in more than two-dimensional Hilbert spaces are achievable. In a tailored photonic lattice, we realize time-independent quantum-driven harmonic oscillators initially prepared in the vacuum state and achieve a measurement of the Aharonov-Anandan phase via integrated interferometry.

New Sesquiterpenoids from the Edible Mushroom Pleurotus Cystidiosus and Their Inhibitory Activity Against α-glucosidase and PTP1B

Fitoterapia. Jun, 2016  |  Pubmed ID: 27085303

Nine new sesquiterpenoids, clitocybulol derivatives, clitocybulols G-O (1-9) and three known sesquiterpenoids, clitocybulols C-E (10-12), were isolated from the solid culture of the edible fungus Pleurotus cystidiosus. The structures of compounds 1-12 were determined by spectroscopic methods. The absolute configurations of compounds 1-9 were assigned via the circular dichroism (CD) data analysis. Compounds 1, 6 and 10 showed moderate inhibitory activity against protein tyrosine phosphatase-1B (PTP1B) with IC50 values of 49.5, 38.1 and 36.0μM, respectively.

Inverted Organic Photovoltaic Cells

Chemical Society Reviews. May, 2016  |  Pubmed ID: 27087582

The advance in lifestyle, modern industrialization and future technological revolution are always at high expense of energy consumption. Unfortunately, there exist serious issues such as limited storage, high cost and toxic contamination in conventional fossil fuel energy sources. Instead, solar energy represents a renewable, economic and green alternative in the future energy market. Among the photovoltaic technologies, organic photovoltaics (OPVs) demonstrate a cheap, flexible, clean and easy-processing way to convert solar energy into electricity. However, OPVs with a conventional device structure are still far away from industrialization mainly because of their short lifetime and the energy-intensive deposition of top metal electrode. To address the stability and cost issue simultaneously, an inverted device structure has been introduced into OPVs, bridging laboratory research with practical application. In this review, recent progress in device structures, working mechanisms, functions and advances of each component layer as well their correlations with the efficiency and stability of inverted OPVs are reviewed and illustrated.

Isoform Switching and Exon Skipping Induced by the DNA Methylation Inhibitor 5-Aza-2'-deoxycytidine

Scientific Reports. 2016  |  Pubmed ID: 27090213

DNA methylation in gene promoters leads to gene silencing and is the therapeutic target of methylation inhibitors such as 5-Aza-2'-deoxycytidine (5-Aza-CdR). By analyzing the time series RNA-seq data (days 5, 9, 13, 17) obtained from human bladder cells exposed to 5-Aza-CdR with 0.1 uM concentration, we showed that 5-Aza-CdR can affect isoform switching and differential exon usage (i.e., exon-skipping), in addition to its effects on gene expression. We identified more than 2,000 genes with significant expression changes after 5-Aza-CdR treatment. Interestingly, 29 exon-skipping events induced by treatment were identified and validated experimentally. Particularly, exon-skipping event in Enhancer of Zeste Homologue 2 (EZH2) along with expression changes showed significant down regulation on Day 5 and Day 9 but returned to normal level on Day 13 and Day 17. EZH2 is a component of the multi-subunit polycomb repressive complex PRC2, and the down-regulation of exon-skipping event may lead to the regain of functional EZH2 which was consistent with our previous finding that demethylation may cause regain of PRC2 in demethylated regions. In summary, our study identified pervasive transcriptome changes of bladder cancer cells after treatment with 5-Aza-CdR, and provided valuable insights into the therapeutic effects of 5-Aza-CdR in current clinical trials.

Common Susceptibility Variants Are Shared Between Schizophrenia and Psoriasis in the Han Chinese Population

Journal of Psychiatry & Neuroscience : JPN. Apr, 2016  |  Pubmed ID: 27091718

Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data.

Reversion of AHRR Demethylation Is a Quantitative Biomarker of Smoking Cessation

Frontiers in Psychiatry. 2016  |  Pubmed ID: 27092088

Smoking is the largest preventable cause of morbidity and mortality in the world. Although there are effective pharmacologic and behavioral treatments for smoking cessation, our inability to objectively quantify smokers' progress in decreasing smoking has been a barrier to both clinical and research efforts. In prior work, we and others have shown that DNA methylation at cg05575921, a CpG residue in the aryl hydrocarbon receptor repressor (AHRR), can be used to determine smoking status and infer cigarette consumption history. In this study, we serially assessed self-report and existing objective markers of cigarette consumption in 35 subjects undergoing smoking cessation therapy, then quantified DNA methylation at cg05575921 at study entry and three subsequent time points. Five subjects who reported serum cotinine and exhaled carbon monoxide verified smoking abstinence for the 3 months prior to study exit averaged a 5.9% increase in DNA methylation at cg05575921 (p < 0.004) over the 6-month study. Although the other 30 subjects did not achieve smoking cessation at the 6-month time point, their self-reported reduction of cigarette consumption (mean = 6 cigarettes/day) was associated with a 2.8% increase DNA methylation at cg05575921 (p < 0.05). Finally, a survey of subjects as they exited the study demonstrated strong support for the clinical use of epigenetic biomarkers. We conclude that AHRR methylation status is a quantifiable biomarker for progress in smoking cessation that could have substantial impact on both smoking cessation treatment and research.

Regulation of LncRNA and Its Role in Cancer Metastasis

Oncology Research. 2016  |  Pubmed ID: 27098144

Metastasis is the primary cause of cancer-related death all over the world. Metastasis is a process by which cancer spreads from the place at which it first arose to distant locations in the body. It is well known that several steps are necessary for this process, including cancer cell epithelial-mesenchymal transition (EMT), cell migration, resistance to anoikis, and angiogenesis. Therefore, investigating the molecular mechanism of regulating cancer metastasis progress may provide helpful insights in the development of efficient diagnosis and therapeutic strategy. Recent studies have indicated that long noncoding RNAs (lncRNAs) play important roles in cancer metastasis. lncRNAs are the nonprotein coding RNAs that have a size longer than 200 nucleotides. More and more studies have indicated that lncRNAs are involved in a broad range of biological processes and are associated with many diseases, such as cancer. The role of lncRNAs in cancer metastasis has been widely studied; however, lncRNAs are mainly involved in the EMT process on the current literature. This review focuses on the mechanisms underlying the role of lncRNAs in cancer metastasis.

Gene Expression Analysis and SNP/InDel Discovery to Investigate Yield Heterosis of Two Rubber Tree F1 Hybrids

Scientific Reports. 2016  |  Pubmed ID: 27108962

As an important industrial material, natural rubber is mainly harvested from the rubber tree. Rubber tree breeding is inefficient, expensive and time-consuming, whereas marker-assisted selection is a feasible method for early selection of high-yield hybrids. We thus sequenced and analyzed the transcriptomes of two parent rubber trees (RRIM 600 and PR 107) and their most productive hybrids (RY 7-33-97 and RY 7-20-59) to understand their gene expression patterns and genetic variations including single nucleotide polymorphisms (SNPs) and small insertions/deletions (InDels). We discovered >31,000 genetic variations in 112,702 assembled unigenes. Our results showed that the higher yield in F1 hybrids was positively associated with their higher genome heterozygosity, which was further confirmed by genotyping 10 SNPs in 20 other varieties. We also showed that RY 7-33-97 and RY 7-20-59 were genetically closer to RRIM 600 and PR 107, respectively, in agreement with both their phenotypic similarities and gene expression profiles. After identifying ethylene- and jasmonic acid-responsive genes at the transcription level, we compared and analyzed the genetic variations underlying rubber biosynthesis and the jasmonic acid and ethylene pathways in detail. Our results suggest that genome-wide genetic variations play a substantive role in maintaining rubber tree heterosis.

Corrigendum to "The Radiological Findings of Chordoid Glioma: Report of Two Cases, One Case with MR Spectroscopy" [Clin Imaging 39 (2015) 1086-1089]

Clinical Imaging. May-Jun, 2016  |  Pubmed ID: 27133706

Early Vitreomacular Separation with Delayed Macular Hole Closure After Ocriplasmin Treatment

Indian Journal of Ophthalmology. Mar, 2016  |  Pubmed ID: 27146933

Based on the indications, one-third to one-half of patients can achieve full-thickness macular hole (FTMH) closure with or without the separation of vitreomacular adhesion (VMA) within 28 days of ocriplasmin treatment. The authors report the case of a 63-year-old man with early VMA separation and delayed FTMH closure after ocriplasmin treatment. Four weeks posttreatment, the posterior vitreous detachment occurred at the optic disk, and the macular hole (MH) started decreasing thereafter. MH closure was finally achieved at 10 weeks posttreatment, leaving minimal subretinal fluid. The patient's vision improved from 0.8 LogMAR (pretreatment) to 0.3 LogMAR (12 weeks posttreatment). This case suggests that FTMH closure can be achieved within 28 days of ocriplasmin treatment.

Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials

The Oncologist. Jun, 2016  |  Pubmed ID: 27151654

The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF, ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) test, in clinical practice.

Two-dimensional GaSe/MoSe2 Misfit Bilayer Heterojunctions by Van Der Waals Epitaxy

Science Advances. Apr, 2016  |  Pubmed ID: 27152356

Two-dimensional (2D) heterostructures hold the promise for future atomically thin electronics and optoelectronics because of their diverse functionalities. Although heterostructures consisting of different 2D materials with well-matched lattices and novel physical properties have been successfully fabricated via van der Waals (vdW) epitaxy, constructing heterostructures from layered semiconductors with large lattice misfits remains challenging. We report the growth of 2D GaSe/MoSe2 heterostructures with a large lattice misfit using two-step chemical vapor deposition (CVD). Both vertically stacked and lateral heterostructures are demonstrated. The vertically stacked GaSe/MoSe2 heterostructures exhibit vdW epitaxy with well-aligned lattice orientation between the two layers, forming a periodic superlattice. However, the lateral heterostructures exhibit no lateral epitaxial alignment at the interface between GaSe and MoSe2 crystalline domains. Instead of a direct lateral connection at the boundary region where the same lattice orientation is observed between GaSe and MoSe2 monolayer domains in lateral GaSe/MoSe2 heterostructures, GaSe monolayers are found to overgrow MoSe2 during CVD, forming a stripe of vertically stacked vdW heterostructures at the crystal interface. Such vertically stacked vdW GaSe/MoSe2 heterostructures are shown to form p-n junctions with effective transport and separation of photogenerated charge carriers between layers, resulting in a gate-tunable photovoltaic response. These GaSe/MoSe2 vdW heterostructures should have applications as gate-tunable field-effect transistors, photodetectors, and solar cells.

Electronic and Magnetic Properties of TTF and TCNQ Covered Co Thin Films

The Journal of Chemical Physics. May, 2016  |  Pubmed ID: 27155648

Interfacial effects like orbital hybridization and charge transfer strongly influence the transfer of spins from ferromagnetic metals to organic semiconductors and can lead to the formation of interfacial states with distinct magnetic properties. The changes in the electronic and magnetic properties of a thin Co film upon adsorption of a layer of either the molecular organic electron donor tetrathiafulvalene (TTF) or the acceptor tetracyanoquinodimethane (TCNQ) have been investigated by X-ray absorption spectroscopy and X-ray magnetic circular dichroism using synchrotron radiation. Clear differences between the spectra of the adsorbed molecules and the neutral molecules show the hybridization of the molecular orbitals with the Co interface. Deposition of both organic materials leads to a small increase of the ratio of the orbital magnetic moment to the spin magnetic moment of the Co atoms at the interface. The main effect of overlayer deposition is a modification of the magnetic hysteresis of the Co film: The TCNQ slightly reduces the coercivity of the Co, while the TTF increases the coercivity by a factor of ∼1.5. These complementary effects of either a molecular organic electron donor or acceptor on the interfacial properties of a metal ferromagnetic thin film are a promising result for the controlled modification of the magnetic structure of hybrid interfaces.

Compression Icing of Room-temperature NaX Solutions (X = F, Cl, Br, I)

Physical Chemistry Chemical Physics : PCCP. May, 2016  |  Pubmed ID: 27156887

In situ Raman spectroscopy revealed that transiting H2O/NaX (∼64) solutions into an ice VI phase and then into an ice VII phase at a temperature of 298 K requires excessive pressures with respect to pure water. The increase of the critical pressures varies with the solute type in the Hofmeister series order: X = I > Br > Cl > F ∼ 0. The results suggest that the solute hydration creates electric fields that lengthen and soften the O:H nonbond and meanwhile shorten and stiffen the H-O bond through O-O Coulomb repulsion. Compression, however, does the opposite to solute electrification upon the O:H-O bond relaxation. Therefore, compression of the aqueous solutions recovers the electrification-deformed O:H-O bond first and then proceeds to the phase transitions, which requires excessive energy for the same sequence of phase transitions. Ice exclusion of solute disperses the frequencies of characteristic phonons and the critical pressures with unlikely new bond formation.

Treatment with Isorhamnetin Protects the Brain Against Ischemic Injury in Mice

Neurochemical Research. Aug, 2016  |  Pubmed ID: 27161367

Ischemic stroke is a major cause of morbidity and mortality, yet lacks effective neuroprotective treatments. The aim of this work was to investigate whether treatment with isorhamnetin protected the brain against ischemic injury in mice. Experimental stroke mice underwent the filament model of middle cerebral artery occlusion with reperfusion. Treatment with isorhamnetin or vehicle was initiated immediately at the onset of reperfusion. It was found that treatment of experimental stroke mice with isorhamnetin reduced infarct volume and caspase-3 activity (a biomarker of apoptosis), and improved neurological function recovery. Treatment of experimental stroke mice with isorhamnetin attenuated cerebral edema, improved blood-brain barrier function, and upregulated gene expression of tight junction proteins including occludin, ZO-1, and claudin-5. Treatment of experimental stroke mice with isorhamnetin activated Nrf2/HO-1, suppressed iNOS/NO, and led to reduced formation of MDA and 3-NT in ipsilateral cortex. In addition, treatment of experimental stroke mice with isorhamnetin suppressed activity of MPO (a biomarker of neutrophil infiltration) and reduced protein levels of IL-1β, IL-6, and TNF-α in ipsilateral cortex. Furthermore, it was found that treatment of experimental stroke mice with isorhamnetin reduced mRNA and protein expression of NMDA receptor subunit NR1 in ipsilateral cortex. In conclusion, treatment with isorhamnetin protected the brain against ischemic injury in mice. Isorhamnetin could thus be envisaged as a countermeasure for ischemic stroke but remains to be tested in humans.

Polyphenol-Rich Propolis Extracts Strengthen Intestinal Barrier Function by Activating AMPK and ERK Signaling

Nutrients. 2016  |  Pubmed ID: 27164138

Propolis has abundant polyphenolic constituents and is used widely as a health/functional food. Here, we investigated the effects of polyphenol-rich propolis extracts (PPE) on intestinal barrier function in human intestinal epithelial Caco-2 cells, as well as in rats. In Caco-2 cells, PPE increased transepithelial electrical resistance and decreased lucifer yellow flux. PPE-treated cells showed increased expression of the tight junction (TJ) loci occludin and zona occludens (ZO)-1. Confocal microscopy showed organized expressions in proteins related to TJ assembly, i.e., occludin and ZO-1, in response to PPE. Furthermore, PPE led to the activation of AMPK, ERK1/2, p38, and Akt. Using selective inhibitors, we found that the positive effects of PPE on barrier function were abolished in cells in which AMPK and ERK1/2 signaling were inhibited. Moreover, rats fed a diet supplemented with PPE (0.3% in the diet) exhibited increased colonic epithelium ZO-1 expression. Overall, these data suggest that PPE strengthens intestinal barrier function by activating AMPK and ERK signaling and provide novel insights into the potential application of propolis for human gut health.

Relevance of Serum Interleukin-33 and ST2 Levels and the Natural Course of Chronic Hepatitis B Virus Infection

BMC Infectious Diseases. 2016  |  Pubmed ID: 27180842

Interleukin-33 (IL-33) and ST2 have been demonstrated to be associated with liver damage. However, their potential value in hepatitis B virus (HBV) infection remains unknown. This study was designed to investigate the change of serum IL-33 and ST2 levels in the natural course of chronic HBV infection.

Gallbladder Tuberculosis Mimicking Gallbladder Carcinoma: A Case Report and Literature Review

Case Reports in Hepatology. 2016  |  Pubmed ID: 27200195

Gallbladder tuberculosis (GT) is extremely rare, and it is difficult to differentiate from other gallbladder diseases, such as gallbladder carcinoma and Xanthogranulomatous Cholecystitis. A correct preoperative diagnosis of GT is difficult. The final diagnosis is usually made postoperatively according to surgical biopsy. Here, we report a case of a patient who underwent surgery with the preoperative diagnosis of gallbladder carcinoma. We reviewed the literature and present the process of differential diagnosis between two or more conditions that share similar signs or symptoms.

Clinical Application of an Original Vascular Anastomosis: A Clinical Multicenter Study

Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. Apr, 2016  |  Pubmed ID: 27206627

Vascular anastomosis is the most important technical step required for the possibility of free tissue transfer, and mismatch of the donor and recipient vessel size is the most common surgical challenge. As recent reports have described a new method (Ren anastomosis) to resolve this challenge, the goal of this study was to assess these newly described microvascular anastomosis methods.

A Noninvasive Model to Predict Liver Histology in HBeAg-positive Chronic Hepatitis B with Alanine Aminotransferase ≤2upper Limit of Normal

Journal of Gastroenterology and Hepatology. May, 2016  |  Pubmed ID: 27207016

Liver biopsy remains the gold standard to evaluate liver histology. However, it has several limitations. This study aims to construct a noninvasive model to predict liver histology for commencing antiviral therapy in HBeAg-positive chronic hepatitis B (CHB) with aminotransferase (ALT) ≤2upper limit of normal (ULN).

Comprehensive Genomic Profiling of Clinically Advanced Medullary Thyroid Carcinoma

Oncology. 2016  |  Pubmed ID: 27207748

The aim of this study was to determine the genomic alterations of cancer-related genes in advanced medullary thyroid carcinoma during the course of clinical care.

Polarized Emission from CsPbX3 Perovskite Quantum Dots

Nanoscale. Jun, 2016  |  Pubmed ID: 27211018

Compared to organic/inorganic hybrid perovskites, full inorganic perovskite quantum dots (QDs) exhibit higher stability. In this study, full inorganic CsPbX3 (X = Br, I and mixed halide systems Br/I) perovskite QDs have been synthesized and interestingly, these QDs showed highly polarized photoluminescence which is systematically studied for the first time. Furthermore, the polarization of CsPbI3 was as high as 0.36 in hexane and 0.40 as a film. The CsPbX3 perovskite QDs with high polarization properties indicate that they possess great potential for application in new generation displays with wide colour gamut and low power consumption.

The Value of Preoperative Neutrophil to Lymphocyte Ratio in Indicating Lymph Node Metastasis in Patients with Resectable T2 Stage Gastric Adenocarcinoma

Clinical Laboratory. 2016  |  Pubmed ID: 27215086

Lymph node metastasis (LNM) is closely associated with poor prognosis in patients with resectable T2 stage gastric adenocarcinoma (RT2-GA). Preoperative blood neutrophil to lymphocyte ratio (NLR) has been identified to be a very valuable predictor for prognosis in patients with diverse cancers. The aim of this investigation was to assess the relationship between NLR and LNM in RT2-GA.

Haploidentical Hematopoietic Stem Cell Transplantation Without Total Body Irradiation for Pediatric Acute Leukemia: a Single-center Experience

OncoTargets and Therapy. 2016  |  Pubmed ID: 27217774

Hematopoietic stem cell transplantation (HSCT) is a promising method for therapy of pediatric patients with acute leukemia. However, less availability of matched donors limited its wide application. Recently, haploidentical HSCT has become a great resource. Here, we have retrospectively reported our experience of 20 pediatric patients with acute leukemia who underwent haploidentical HSCT without total body irradiation (TBI) myeloablative regimen in our center from November 2007 to June 2014. All the patients attained successful HSCT engraftment in terms of myeloid and platelet recovery. Thirteen patients developed grade I-IV acute graft-versus-host disease (a-GVHD). The incidence of grade I-II a-GVHD, grade III-IV a-GVHD, and chronic GVHD (c-GVHD) was 45%, 20%, and 25%, respectively. The mean myeloid and platelet recovery time was 13.20±2.41 and 19.10±8.37 days. The median follow-up time was 43.95±29.26 months. During the follow-up, three patients died. The overall survival (OS) rate was 85%. The present study indicated that haploidentical HSCT without TBI myeloablative regimen significantly improved the OS rate of pediatric patients with acute leukemia.

Aberrant Structural and Functional Connectivity in the Salience Network and Central Executive Network Circuit in Schizophrenia

Neuroscience Letters. Aug, 2016  |  Pubmed ID: 27233217

Consistent structural and functional abnormities have been detected in the salience network (SN) and the central-executive network (CEN) in schizophrenia. SN, known for its critical role in switching CEN and default-mode network (DMN) during cognitively demanding tasks, is proved to show aberrant regulation on the interaction between DMN and CEN in schizophrenia. However, it has not been elucidated whether there is a direct alteration of structural and functional connectivity between SN and CEN. 22 schizophrenia patients and 21 healthy controls were recruited for functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) in present study. The results show that schizophrenia patients had lower fractional anisotropy (FA) in right inferior long fasciculus (ILF), left inferior fronto-occipital fasciculus (IFOF) and callosal body than healthy controls. Significantly reduced functional connectivity was also found between right fronto-insular cortex (rFIC) and right posterior parietal cortex (rPPC). FA in right ILF was positively correlated with the functional connectivity of rFIC-rPPC. Therefore, we proposed a disruption of structural and functional connectivity and a positive anatomo-functional relationship in SN-CEN circuit, which might account for a core feature of schizophrenia.

Comparison of the Outcomes of Hepatocellular Carcinoma After Hepatectomy Between Two Regional Medical Centers in China and Japan

Asian Journal of Surgery / Asian Surgical Association. May, 2016  |  Pubmed ID: 27236717

Hepatocellular carcinoma (HCC) is a common malignant disease of the liver in China and Japan. The purpose of this study was to compare the outcomes of HCC patients after hepatectomy between two regional medical centers in China and Japan.

Clinical Relevance of HLA Gene Variants in HBV Infection

Journal of Immunology Research. 2016  |  Pubmed ID: 27243039

Host gene variants may influence the natural history of hepatitis B virus (HBV) infection. The human leukocyte antigen (HLA) system, the major histocompatibility complex (MHC) in humans, is one of the most important host factors that are correlated with the clinical course of HBV infection. Genome-wide association studies (GWASs) have shown that single nucleotide polymorphisms (SNPs) near certain HLA gene loci are strongly associated with not only persistent HBV infection but also spontaneous HBV clearance and seroconversion, disease progression, and the development of liver cirrhosis and HBV-related hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). These variations also influence the efficacy of interferon (IFN) and nucleot(s)ide analogue (NA) treatment and response to HBV vaccines. Meanwhile, discrepant conclusions were reached with different patient cohorts. It is therefore essential to identify the associations of specific HLA allele variants with disease progression and viral clearance in chronic HBV infection among different ethnic populations. A better understanding of HLA polymorphism relevance in HBV infection outcome would enable us to elucidate the roles of HLA SNPs in the pathogenesis and clearance of HBV in different areas and ethnic groups, to improve strategies for the prevention and treatment of chronic HBV infection.

Effect of Oxidation Condition on Growth of N: ZnO Prepared by Oxidizing Sputtering Zn-N Film

Nanoscale Research Letters. Dec, 2016  |  Pubmed ID: 27251324

Nitrogen-doped zinc oxide (N: ZnO) films have been prepared by oxidizing reactive RF magnetron-sputtering zinc nitride (Zn-N) films. The effect of oxidation temperature and oxidation time on the growth, transmittance, and electrical properties of the film has been explored. The results show that both long oxidation time and high oxidation temperature can obtain the film with a good transmittance (over 80 % for visible and infrared light) and a high carrier concentration. The N: ZnO film exhibits a special growth model with the oxidation time and is first to form a N: ZnO particle on the surface, then to become a N: ZnO layer, and followed by the inside Zn-N segregating to the surface to oxidize N: ZnO. The surface particle oxidized more adequately than the inside. However, the X-ray photoemission spectroscopy results show that the lower N concentration results in the lower N substitution in the O lattice (No). This leads to the formation of n-type N: ZnO and the decrease of carrier concentration. Thus, this method can be used to tune the microstructure, optical transmittance, and electrical properties of the N: ZnO film.

Synergistic Chemopreventive Effects of Curcumin and Berberine on Human Breast Cancer Cells Through Induction of Apoptosis and Autophagic Cell Death

Scientific Reports. 2016  |  Pubmed ID: 27263652

Curcumin (CUR) and berberine (BBR) are renowned natural compounds that exhibit potent anticancer activities through distinct molecular mechanisms. However, the anticancer capacity of either CUR or BBR is limited. This prompted us to investigate the chemopreventive potential of co-treatment of CUR and BBR against breast cancers. The results showed that CUR and BBR in combination synergistically inhibited the growth of both MCF-7 and MDA-MB-231 breast cancer cells than the compounds used alone. Further study confirmed that synergistic anti-breast cancer activities of co-treatment of these two compounds was through inducing more apoptosis and autophagic cell death (ACD). The co-treatment-induced apoptosis was caspase-dependent and through activating ERK pathways. Our data also demonstrated that co-treatment of CUR and BBR strongly up-regulated phosphorylation of JNK and Beclin1, and decreased phosphorylated Bcl-2. Inhibition of JNK by SP600125 markedly decreased LC3-II and Beclin1, restored phosphorylated Bcl-2, and reduced the cytotoxicity induced by the two compounds in combination. These results strongly suggested that JNK/Bcl-2/Beclin1 pathway played a key role in the induction of ACD in breast cancer cells by co-treatment of CUR and BBR. This study provides an insight into the potential application of curcumin and berberine in combination for the chemoprevention and treatment of breast cancers.

SQSTM1 Mutations and Glaucoma

PloS One. 2016  |  Pubmed ID: 27275741

Glaucoma is the most common cause of irreversible blindness worldwide. One subset of glaucoma, normal tension glaucoma (NTG) occurs in the absence of high intraocular pressure. Mutations in two genes, optineurin (OPTN) and TANK binding kinase 1 (TBK1), cause familial NTG and have known roles in the catabolic cellular process autophagy. TKB1 encodes a kinase that phosphorylates OPTN, an autophagy receptor, which ultimately activates autophagy. The sequestosome (SQSTM1) gene also encodes an autophagy receptor and also is a target of TBK1 phosphorylation. Consequently, we hypothesized that mutations in SQSTM1 may also cause NTG. We tested this hypothesis by searching for glaucoma-causing mutations in a cohort of NTG patients (n = 308) and matched controls (n = 157) using Sanger sequencing. An additional 1098 population control samples were also analyzed using whole exome sequencing. A total of 17 non-synonymous mutations were detected which were not significantly skewed between cases and controls when analyzed separately, or as a group (p > 0.05). These data suggest that SQSTM1 mutations are not a common cause of NTG.

Functional Connectivity Change of Brain Default Mode Network in Breast Cancer Patients After Chemotherapy

Neuroradiology. Jun, 2016  |  Pubmed ID: 27278455

Complaint about attention disorders is common among breast cancer patients who have undergone chemotherapy, which may be associated with the default mode network (DMN). To validate this hypothesis, we investigated the DMN functional connectivity (FC) change and its relationship with the attention function in breast cancer patients (BC) using resting-state functional magnetic resonance imaging (rs-fMRI).

Nonamplification ERBB2 Genomic Alterations in 5605 Cases of Recurrent and Metastatic Breast Cancer: An Emerging Opportunity for Anti-HER2 Targeted Therapies

Cancer. Sep, 2016  |  Pubmed ID: 27284958

Activating, nonamplification ERBB2 mutations (ERBB2mut) are not detected by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), but are detected by DNA sequencing and may predict clinical responses to human epidermal growth factor receptor (HER2)-targeted therapy. The authors queried 5605 advanced/metastatic breast cancers (mBC) to uncover the frequency of ERBB2mut genomic alterations. Clinical responses to anti-HER2 therapeutics were identified.

Optimization of Lipase Production from a Novel Strain Thalassospira Permensis M35-15 Using Response Surface Methodology

Bioengineered. Jun, 2016  |  Pubmed ID: 27285376

Lipases can catalyze the hydrolysis of glycerol, esters and long chain fatty acids. A lipase producing isolate M35-15 was screened and identified as Thalassospira permensis using 16S rRNA gene sequence analysis. To our knowledge this is the first report on Thalassospira permensis producing lipases. In this paper the optimization of medium composition for the increase in bacterial lipase was achieved using statistical methods. Firstly the key ingredients were selected by Plackett-Burman experimental design, then the levels of the ingredients were optimized using central composite design of Response Surface Methodology. The predicted optimal lipase activity was 11.49 U under the conditions that medium composition were 5.15 g/l glucose, 11.74 g/l peptone, 6.74 g/l yeast powder and 22.90 g/l olive oil emulsifier.

Renal Denervation Significantly Attenuates Cardiorenal Fibrosis in Rats with Sustained Pressure Overload

Journal of the American Society of Hypertension : JASH. Jul, 2016  |  Pubmed ID: 27288113

To investigate the effects of renal denervation (RDN) on comprehensive cardiac and renal fibrosis in cardiomyopathy. Five weeks after successful transverse aortic constriction (TAC)-induced cardiomyopathy model building, Sprague-Dawley rats were randomly assigned to three groups: (1) RDN, (2) sham, and (3) losartan. Sham TAC rats served as control group. Compared with control, TAC groups showed a significant decrease in left ventricle ejection fraction and increase in ventricular septum thickness and left atrium diameter on echocardiography after 5 weeks. At 10 weeks post-TAC, venous blood samples were collected for fibrosis biochemical assay. Heart and kidney samples were also harvested for fibrosis pathophysiological detection. Cardiac and renal fibrosis quantity results showed that, compared with sham group, collagen volume fraction was significantly decreased in RDN group more than in losartan group. Biochemical parameters such as tumor necrosis factor α, aldosterone, and B-type natriuretic peptide levels as well as biomarkers for fibrosis such as procollagen type I N-terminal propeptide and procollagen type III N-terminal propeptide concentrations were significantly decreased in RDN group in comparison with sham. In addition, compared with sham group, left ventricle tissue protein expression of transforming growth factor-β1 and angiotensin II type I receptor was downregulated, and angiotensin-converting enzyme 2 was upregulated in RDN but not in losartan group. RDN significantly attenuates cardiac and renal fibrosis in cardiomyopathy. Differing from losartan, which only has angiotensin II type I receptor inhibition effects, RDN comprehensively suppresses cardiac and renal fibrogenesis through multiple pathways.

Unique Genomic Features in Adolescent and Young Adult, As Compared to Older Adult, Non-Hodgkin Lymphoma and Potential Therapeutic Targets

British Journal of Haematology. Jun, 2016  |  Pubmed ID: 27291498

Anomalous Photoluminescence in InP1-xBix

Scientific Reports. 2016  |  Pubmed ID: 27291823

Low temperature photoluminescence (PL) from InP1-xBix thin films with Bi concentrations in the 0-2.49% range reveals anomalous spectral features with strong and very broad (linewidth of 700 nm) PL signals compared to other bismide alloys. Multiple transitions are observed and their energy levels are found much smaller than the band-gap measured from absorption measurements. These transitions are related to deep levels confirmed by deep level transient spectroscopy, which effectively trap free holes and enhance radiative recombination. The broad luminescence feature is beneficial for making super-luminescence diodes, which can theoretically enhance spatial resolution beyond 1 μm in optical coherent tomography (OCT).

Boosting the Power of the Sequence Kernel Association Test by Properly Estimating Its Null Distribution

American Journal of Human Genetics. Jul, 2016  |  Pubmed ID: 27292111

The sequence kernel association test (SKAT) is probably the most popular statistical test used in rare-variant association studies. Its null distribution involves unknown parameters that need to be estimated. The current estimation method has a valid type I error rate, but the power is compromised given that all subjects are used for estimation. I have developed an estimation method that uses only control subjects. Named SKAT+, this method uses the same test statistic as SKAT but differs in the way the null distribution is estimated. Extensive simulation studies and applications to data from the Genetic Analysis Workshop 17 and the Ocular Hypertension Treatment Study demonstrated that SKAT+ has superior power over SKAT while maintaining control over the type I error rate. This method is applicable to extensions of SKAT in the literature.

A Combination of Targeted Therapy with Chemotherapy Backbone Induces Response in a Treatment-Resistant Triple-Negative MCL1-Amplified Metastatic Breast Cancer Patient

Case Reports in Oncology. Jan-Apr, 2016  |  Pubmed ID: 27293397

After failure of anthracycline- and platinum-based therapy, no effective therapies exist for management of metastatic triple-negative breast cancer (TNBC). We report a case of metastatic TNBC harboring MCL1 amplification, as identified by comprehensive genomic profiling in the course of clinical care. MCL1 is an antiapoptotic gene in the BCL2 family, and MCL1 amplification is common in TNBC (at least 20%). A personalized dose-reduced regimen centered on a combination of sorafenib and vorinostat was implemented, based on preclinical evidence demonstrating treatment synergy in the setting of MCL1 amplification. Although hospice care was being considered before treatment initiation, the personalized regimen yielded 6 additional months of life for this patient. Further rigorous studies are needed to confirm that this regimen or derivatives thereof can benefit the MCL1-amplified subset of TNBC patients.

Isomeric Thermally Activated Delayed Fluorescence Emitters for Color Purity-Improved Emission in Organic Light-Emitting Devices

ACS Applied Materials & Interfaces. Jul, 2016  |  Pubmed ID: 27296853

To improve the color purity of thermally activated delayed fluorescence (TADF) emitters, two isomeric compounds, oPTC (5'-(phenoxazin-10-yl)-[1,1':3',1″-terphenyl]-2'-carbonitrile) and mPTC (2'-(phenoxazin-10-yl)-[1,1':3',1″-terphenyl]-5'-carbonitrile), were designed and synthesized with same skeleton but different molecular restrictions. Both compounds exhibit similar highest occupied molecular orbital and lowest unoccupied molecular orbital distributions and energy levels, photophysical properties in nonpolar cyclohexane solution, and high external quantum efficiencies (19.9% for oPTC and 17.4% for mPTC) in the devices. With the increased molecular space restriction induced by the additional phenyl substitutions at meta-position of the cyano group from mPTC to oPTC, much weaker positive solvatochromic effect is observed for mPTC. And the color purity of emission from mPTC (full width at half-maximum (fwhm) of 86 nm) is also improved contrasted with that of oPTC (fwhm of 97 nm) in the devices. These results prove that increased restriction of the molecular structure is a simple and effective method to improve the color purity of the TADF emitters.

A Single-stranded {Gd18} Nanowheel with a Symmetric Polydentate Diacylhydrazone Ligand

Chemical Communications (Cambridge, England). Jul, 2016  |  Pubmed ID: 27296972

An unprecedented {Gd18} nanowheel was solvothermally synthesized with a novel diacylhydrazone ligand. It features a rare single-stranded skeleton just like a Reuleaux triangle with vertices buckled in, represents the highest nuclearity and largest size in lanthanide (Ln) wheels reported so far, and shows a large magnetocaloric effect (MCE).

Erratum To: Heritability and Genome-wide Analyses of Problematic Peer Relationships During Childhood and Adolescence

Human Genetics. Aug, 2016  |  Pubmed ID: 27299648

Extracellular MRNA Detected by Tethered Lipoplex Nanoparticle Biochip for Lung Adenocarcinoma Detection

American Journal of Respiratory and Critical Care Medicine. Jun, 2016  |  Pubmed ID: 27304243

Venlafaxine Treatment Reduces the Deficit of Executive Control of Attention in Patients with Major Depressive Disorder

Scientific Reports. 2016  |  Pubmed ID: 27306061

Attention plays an essential role in supporting other cognitive functions and behavior, and disturbance of attention is one of the most common symptoms in major depressive disorder (MDD). Although treatment with venlafaxine for MDD symptoms has been shown to reduce deficits in cognition and emotion regulation, it remains unclear whether venlafaxine improves specific attentional functions. We used the Attention Network Test to measure the attentional functions of alerting, orienting, and executive control before and after treatment with venlafaxine in patients with MDD compared to untreated healthy controls. Before treatment, the MDD group showed a selective impairment in alerting and executive control of attention, while there were no significant group differences in the orienting function. The interaction between group and session was significant for executive control, and after treatment with venlafaxine, the performance of the MDD group on executive control of attention was not significantly different from that of controls. Reported symptoms of MDD were also significantly reduced after treatment with venlafaxine. These results demonstrate that treatment with venlafaxine selectively normalizes the executive control function of attention in addition to improving clinical symptoms in MDD.

Interlayer Coupling in Twisted WSe2/WS2 Bilayer Heterostructures Revealed by Optical Spectroscopy

ACS Nano. Jul, 2016  |  Pubmed ID: 27309275

van der Waals (vdW) heterostructures are promising building blocks for future ultrathin electronics. Fabricating vdW heterostructures by stamping monolayers at arbitrary angles provides an additional range of flexibility to tailor the resulting properties than could be expected by direct growth. Here, we report fabrication and comprehensive characterizations of WSe2/WS2 bilayer heterojunctions with various twist angles that were synthesized by artificially stacking monolayers of WS2 and WSe2 grown by chemical vapor deposition. After annealing the WSe2/WS2 bilayers, Raman spectroscopy reveals interlayer coupling with the appearance of a mode at 309.4 cm(-1) that is sensitive to the number of WSe2 layers. This interlayer coupling is associated with substantial quenching of the intralayer photoluminescence. In addition, microabsorption spectroscopy of WSe2/WS2 bilayers revealed spectral broadening and shifts as well as a net ∼10% enhancement in integrated absorption strength across the visible spectrum with respect to the sum of the individual monolayer spectra. The observed broadening of the WSe2 A exciton absorption band in the bilayers suggests fast charge separation between the layers, which was supported by direct femtosecond pump-probe spectroscopy. Density functional calculations of the band structures of the bilayers at different twist angles and interlayer distances found robust type II heterojunctions at all twist angles, and predicted variations in band gap for particular atomistic arrangements. Although interlayer excitons were indicated using femtosecond pump-probe spectroscopy, photoluminescence and absorption spectroscopies did not show any evidence of them, suggesting that the interlayer exciton transition is very weak. However, the interlayer coupling for the WSe2/WS2 bilayer heterojunctions indicated by substantial PL quenching, enhanced absorption, and rapid charge transfer was found to be insensitive to the relative twist angle, indicating that stamping provides a robust approach to realize reliable optoelectronics.

Port-site Metastasis As a Primary Complication Following Retroperitoneal Laparoscopic Radical Resection of Renal Pelvis Carcinoma or Nephron-sparing Surgery: A Report of Three Cases and Review of the Literature

Oncology Letters. Jun, 2016  |  Pubmed ID: 27313720

The present study reports the clinical data of two patients with renal pelvis carcinoma and one patient with renal carcinoma who developed port-site metastasis following retroperitoneal laparoscopic surgery. The current study aimed to identify the cause and prognosis of the occurrence of port-site metastasis subsequent to laparoscopic radical resection of renal pelvis carcinoma and nephron-sparing surgery. Post-operative pathology confirmed the presence of high-grade urothelial cell carcinoma in two patients and Fuhrman grade 3 renal clear cell carcinoma in one patient. Port-site metastasis was initially detected 1-7 months post-surgery. The two patients with renal pelvis carcinoma succumbed to the disease 2 and 4 months following the identification of the port-site metastasis, respectively, whereas the patient with renal carcinoma survived with no disease progression during the targeted therapy period. The occurrence of port-site metastasis may be attributed to systemic and local factors. Measures to reduce the development of this complication include strict compliance with the operating guidelines for tumor surgery, avoidance of air leakage at the port-site, complete removal of the specimen with an impermeable bag, irrigation of the laparoscopic instruments and incisional wound with povidone-iodine when necessary, and enhancement of the body's immunity. Close post-operative follow-up observation for signs of recurrence or metastasis is essential, and systemic chemotherapy may be required in patients with high-grade renal pelvis carcinoma and renal carcinoma in order to prolong life expectancy.

Pressure-Induced Structural and Optical Properties of Organometal Halide Perovskite-Based Formamidinium Lead Bromide

The Journal of Physical Chemistry Letters. Jul, 2016  |  Pubmed ID: 27321024

Organometal halide perovskites (OMHPs) are attracting an ever-growing scientific interest as photovoltaic materials with moderate cost and compelling properties. In this Letter, pressure-induced optical and structural changes of OMHP-based formamidinium lead bromide (FAPbBr3) were systematically investigated. We studied the pressure dependence of optical absorption and photoluminescence, both of which showed piezochromism. Synchrotron X-ray diffraction indicated that FAPbBr3 underwent two phase transitions and subsequent amorphization, leading directly to the bandgap evolution with redshift followed by blueshift during compression. Raman experiments illustrated the high pressure behavior of organic cation and the surrounding inorganic octahedra. Additionally, the effect of cation size and the different intermolecular interactions between organic cation and inorganic octahedra result in the fact that FAPbBr3 is less compressible than the reported methylammonium lead bromide (MAPbBr3). High pressure studies of the structural evolution and optical properties of OMHPs provide important clues in optimizing photovoltaic performance and help to design novel OMHPs with higher stimuli-resistant ability.

Innate Immune Targets of Hepatitis B Virus Infection

World Journal of Hepatology. Jun, 2016  |  Pubmed ID: 27330680

Approximately 400 million people are chronically infected with hepatitis B virus (HBV) globally despite the widespread immunization of HBV vaccine and the development of antiviral therapies. The immunopathogenesis of HBV infection is initiated and driven by complexed interactions between the host immune system and the virus. Host immune responses to viral particles and proteins are regarded as the main determinants of viral clearance or persistent infection and hepatocyte injury. Innate immune system is the first defending line of host preventing from virus invasion. It is acknowledged that HBV has developed active tactics to escape innate immune recognition or actively interfere with innate immune signaling pathways and induce immunosuppression, which favor their replication. HBV reduces the expression of pattern-recognition receptors in the innate immune cells in humans. Also, HBV may interrupt different parts of antiviral signaling pathways, leading to the reduced production of antiviral cytokines such as interferons that contribute to HBV immunopathogenesis. A full comprehension of the mechanisms as to how HBV inactivates various elements of the innate immune response to initiate and maintain a persistent infection can be helpful in designing new immunotherapeutic methods for preventing and eradicating the virus. In this review, we aimed to summarize different branches the innate immune targeted by HBV infection. The review paper provides evidence that multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection.

Profiling of 149 Salivary Duct Carcinomas, Carcinoma Ex Pleomorphic Adenomas, and Adenocarcinomas, Not Otherwise Specified Reveals Actionable Genomic Alterations

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Jun, 2016  |  Pubmed ID: 27334835

We sought to identify genomic alterations (GAs) in salivary gland adenocarcinomas, not otherwise specified (NOS), salivary duct carcinomas (SDC), carcinoma ex pleomorphic adenoma (ca ex PA), and salivary carcinoma, NOS.

Intestinally-targeted TGR5 Agonists Equipped with Quaternary Ammonium Have an Improved Hypoglycemic Effect and Reduced Gallbladder Filling Effect

Scientific Reports. 2016  |  Pubmed ID: 27339735

TGR5 activation of enteroendocrine cells increases glucagon-like peptide 1 (GLP-1) release, which maintains glycemic homeostasis. However, TGR5 activation in the gallbladder and heart is associated with severe side effects. Therefore, intestinally-targeted TGR5 agonists were suggested as potential hypoglycemic agents with minimal side effects. However, until now no such compounds with robust glucose-lowering effects were reported, especially in diabetic animal models. Herein, we identify a TGR5 agonist, 26a, which was proven to be intestinally-targeted through pharmacokinetic studies. 26a was used as a tool drug to verify the intestinally-targeted strategy. 26a displayed a robust and long-lasting hypoglycemic effect in ob/ob mice (once a day dosing (QD) and 18-day treatment) owing to sustained stimulation of GLP-1 secretion, which suggested that robust hypoglycemic effect could be achieved with activation of TGR5 in intestine alone. However, the gallbladder filling effect of 26a was rather complicated. Although the gallbladder filling effect of 26a was decreased in mice after once a day dosing, this side effect was still not eliminated. To solve the problem above, several research strategies were raised for further optimization.

Overcoming Foreign-body Reaction Through Nanotopography: Biocompatibility and Immunoisolation Properties of a Nanofibrous Membrane

Biomaterials. Sep, 2016  |  Pubmed ID: 27344368

Implantable immunoisolation membranes need to possess superior biocompatibility to prohibit the fibrotic deposition that would reduce the nutrient supply and impair the viability/function of the encapsulated cells. Here, electrospun membranes based on thermoplastic polyurethane (TPU) were fabricated to contain microfibers (PU-micro) or nanofibers (PU-nano). The two types of membranes were compared in terms of their interaction with macrophage cells and the host tissues. It was found that the fibrous membranes of different topographies possess distinct material properties: PU-nano caused minimal macrophage responses in vitro and in vivo and induced only mild foreign body reactions compared to PU-micro membranes. A flat macroencapsulation device was fabricated using PU-nano membranes and its immunoisolation function investigated in subcutaneous transplantation models. The nanofibrous device demonstrated the capability to effectively shield the allografts from the immune attack of the host. Nanotopography may confer biocompatibility to materials and nanofibrous materials warrant further study for development of "invisible" immunoisolation devices for cell transplantation.

Serum Polychlorinated Biphenyls and Their Hydroxylated Metabolites Are Associated with Demographic and Behavioral Factors in Children and Mothers

Environment International. Sep, 2016  |  Pubmed ID: 27352881

Factors contributing to the inter-individual variation in body burden of polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) have not been fully elucidated. We examined associations between total serum concentrations of 209 PCBs, 64 OH-PCBs, and frequently detected individual congeners with demographic characteristics (age, gender, ethnicity and community of residence), body mass index (BMI or BMI percentile), and breastfeeding history in children and their mothers from 83 U.S. households. There was a significant positive association between age and concentrations of total PCBs and OH-PCBs in mothers. Non-Hispanics had significantly higher concentrations of total PCBs in mothers and OH-PCBs in children than Hispanics. Concentrations of total PCBs were significantly lower in mothers who had longer breastfeeding duration. Living in the Columbus Junction, Iowa community as compared to East Chicago, Indiana was associated with higher total PCBs in children, probably attributable to higher exposures at school. Lower concentrations of OH-PCBs were significantly associated with a higher BMI percentile in children. Congener-specific associations were observed for 30 PCB and 12 OH-PCB congeners and followed comparable trends. To our knowledge, this is the first study to examine factors contributing to variations in serum concentrations of total 209 PCBs and total OH-PCBs in children, as well as to examine ethnic differences in OH-PCB levels. Results from this study revealed that demographic characteristics, body mass index and breastfeeding history are factors that should be considered for human exposure and risk assessment of PCBs and OH-PCBs.

Long-read Sequencing and De Novo Assembly of a Chinese Genome

Nature Communications. 2016  |  Pubmed ID: 27356984

Short-read sequencing has enabled the de novo assembly of several individual human genomes, but with inherent limitations in characterizing repeat elements. Here we sequence a Chinese individual HX1 by single-molecule real-time (SMRT) long-read sequencing, construct a physical map by NanoChannel arrays and generate a de novo assembly of 2.93 Gb (contig N50: 8.3 Mb, scaffold N50: 22.0 Mb, including 39.3 Mb N-bases), together with 206 Mb of alternative haplotypes. The assembly fully or partially fills 274 (28.4%) N-gaps in the reference genome GRCh38. Comparison to GRCh38 reveals 12.8 Mb of HX1-specific sequences, including 4.1 Mb that are not present in previously reported Asian genomes. Furthermore, long-read sequencing of the transcriptome reveals novel spliced genes that are not annotated in GENCODE and are missed by short-read RNA-Seq. Our results imply that improved characterization of genome functional variation may require the use of a range of genomic technologies on diverse human populations.

Exercise Impacts The Global Profile Of MiRNA In Plasma And Skeletal Muscle In Hypertensive Rats: 2627 Board #150 June 3, 9: 30 AM - 11: 00 AM

Medicine and Science in Sports and Exercise. May, 2016  |  Pubmed ID: 27361263

Deep Genetic Connection Between Cancer and Developmental Disorders

Human Mutation. Oct, 2016  |  Pubmed ID: 27363847

Cancer and developmental disorders (DDs) share dysregulated cellular processes such as proliferation and differentiation. There are well-known genes implicated in both in cancer and DDs. In this study, we aim to quantify this genetic connection using publicly available data. We found that among DD patients, germline damaging de novo variants are more enriched in cancer driver genes than non-drivers. We estimate that cancer driver genes comprise about a third of DD risk genes. Additionally, de novo likely-gene-disrupting variants are more enriched in tumor suppressors, and about 40% of implicated de novo damaging missense variants are located in cancer somatic mutation hotspots, indicating that many genes have a similar mode of action in cancer and DDs. Our results suggest that we can view tumors as natural laboratories for assessing the deleterious effects of mutations that are applicable to germline variants and identification of causal genes and variants in DDs.

Plasmonic Zener Tunneling in Binary Graphene Sheet Arrays

Optics Letters. Jul, 2016  |  Pubmed ID: 27367080

We investigate the plasmonic Zener tunneling (ZT) in arrays of weakly coupled graphene sheet waveguides. By alternatively arranging the graphene waveguides with two different chemical potentials, the single surface plasmon polariton (SPP) band splits into two minibands, and tunneling between them occurs at the edge of the Brillouin zone. With a linear gradient of the propagation constant introduced by appropriately tuning the chemical potential distribution over the graphene sheet, the SPPs exhibit a sequence of Bloch oscillations and ZT transitions in the arrays. The simulated tunneling rate coincides with the theoretical analysis based on the coupled-mode theory, which can be tuned by varying the chemical potential difference between adjacent graphene.

Probing Amyloid Beta-induced Cell Death Using a Fluorescence-peptide Conjugate in Alzheimer's Disease Mouse Model

Brain Research. Sep, 2016  |  Pubmed ID: 27369450

With the increasing worldwide incidence of Alzheimer's disease (AD), there is a critical need for the discovery of more effective diagnostic methods. However, development of diagnostic tools in AD has been hindered by obstacles such as the absence of exact biomarkers. Apoptosis caused by amyloid-β (Aβ) plays an important role in AD pathology; therefore, provides an attractive biological target for the diagnosis of AD. The present study aimed to evaluate the potential of small peptide, named ApoPep-1 (Apoptosis-targeting peptide-1) as a new apoptosis imaging agent in AD. The fluorescein-conjugated ApoPep-1, but not the control peptide, targeted apoptotic cells in the brain of amyloid precursor protein (APP)/presenilin 1 (PS1) mice. We also observed fluorescence signals during in vivo imaging of apoptotic cells using ApoPep-1, and fluorescence levels increased in an age-dependent manner in APP/PS1 mice. Ex vivo imaging of isolated brains in APP/PS1 mice further confirmed the targeting of ApoPep-1 to apoptotic cells. The fluorescein-labeled ApoPep-1 co-localized with brain cells such as neurons, astrocytes, and microglia, all of which undergo apoptosis in the APP/PS1 mice brain. These findings demonstrate that ApoPep-1 can target apoptotic brain cells, and be used for experimental investigations relevant to apoptosis in AD.

Impaired Functional Default Mode Network in Patients with Mild Neurological Wilson's Disease

Parkinsonism & Related Disorders. Sep, 2016  |  Pubmed ID: 27372239

Wilson's disease (WD) is an autosomal recessive metabolic disorder characterized by cognitive, psychiatric and motor signs and symptoms that are associated with structural and pathological brain abnormalities, in addition to liver changes. However, functional brain connectivity pattern of WD patients remains largely unknown. In the present study, we investigated functional brain connectivity pattern of WD patients using resting state functional magnetic resonance imaging. Particularly, we studied default mode network (DMN) using posterior cingulate cortex (PCC) based seed functional connectivity analysis and graph theoretic functional brain network analysis tools, and investigated the relationship between the DMN's functional connectivity pattern of WD patients and their attention functions examined using the attention network test (ANT). Our results demonstrated that WD patients had altered DMN's functional connectivity and lower local and global network efficiency compared with normal controls (NCs). In addition, the functional connectivity between left inferior temporal cortex and right lateral parietal cortex was correlated with altering function, one of the attention functions, across WD and NC subjects. These findings indicated that the DMN's functional connectivity was altered in WD patients, which might be correlated with their attention dysfunction.

Promotion of Epithelial-mesenchymal Transition by Frizzled2 is Involved in the Metastasis of Endometrial Cancer

Oncology Reports. Aug, 2016  |  Pubmed ID: 27373314

The Wnt signaling pathway is essential for embryonic development, and genetic alteration in this network is closely correlated with tumorigenesis and progression. Previous research has shown that Wnt receptor Frizzled2 (Fzd2) is elevated in many metastatic cancer cell lines and high grade tumors. Yet, little is known about the Fzd2 expression and activity in human endometrial cancer (EC). In this study, we present evidence of a direct role of Fzd2 in human EC. We found that Fzd2 expression was higher in EC than that in adjacent normal tissues, and was correlated with epithelial‑mesenchymal transition markers. Next, it was determined that the stable overexpression of Fzd2 in HEC-1B and Ishikawa cells promoted cell migration and induced an EMT phenotype. Conversely, RNA interference-mediated depletion of Fzd2 inhibited EC cell migration. Additionally, mechanistic investigation revealed that elevated Fzd2 expression activated canonical Wnt signaling and was blocked by canonical Wnt signaling inhibitor XAV939. However, Fzd2 did not influence the proliferation of EC cells. Thus, Fzd2 may be a potential marker for EC metastasis and a target for future therapies for this disease.

Monomeric C-reactive Protein and Inflammation in Age-related Macular Degeneration

The Journal of Pathology. Jul, 2016  |  Pubmed ID: 27376713

Age-related macular degeneration (AMD) is a devastating disease characterized by central vision loss in elderly individuals. Previous studies have suggested a link between elevated levels of total C-reactive protein (CRP) in the choroid, CFH genotype, and AMD status; however, the structural form of CRP present in the choroid, its relationship to CFH genotype, and its functional consequences have not been assessed. In this report, we studied genotyped human donor eyes (n = 60) and found that eyes homozygous for the high-risk CFH (Y402H) allele had elevated monomeric CRP (mCRP) within the choriocapillaris and Bruch's membrane, compared to those with the low-risk genotype. Treatment of choroidal endothelial cells in vitro with mCRP increased migration rate and monolayer permeability compared to treatment with pCRP or medium alone. Organ cultures treated with mCRP exhibited dramatically altered expression of inflammatory genes as assessed by RNA sequencing, including ICAM-1 and CA4, both of which were confirmed at the protein level. Our data indicate that mCRP is the more abundant form of CRP in human choroid, and that mCRP levels are elevated in individuals with the high-risk CFH genotype. Moreover, pro-inflammatory mCRP significantly affects endothelial cell phenotypes in vitro and ex vivo, suggesting a role for mCRP in choroidal vascular dysfunction in AMD.

RIP3 Induces Ischemic Neuronal DNA Degradation and Programmed Necrosis in Rat Via AIF

Scientific Reports. 2016  |  Pubmed ID: 27377128

We have reported that nuclear translocation of Receptor-interacting protein 3 (RIP3) involves in neuronal programmed necrosis after 20-min global cerebral ischemia/reperfusion (I/R) injury. Herein, the underlying mechanisms and the nuclear role of RIP3 were investigated further. The necroptosis inhibitor necrostatin-1 (Nec-1), the autophagy inhibitor 3-methyladenine (3-MA), and the caspase-3 inhibitor acetyl-L-aspartyl-L-methionyl-L-glutaminyl-L-aspart-1-al (Ac-DMQD-CHO) were administered intracerebroventricularly 1 h before ischemia. Protein expression, location and interaction was determined by western blot, immunofluorescence or immunoprecipitation. Most CA1 neuronal death induced by 20-min global cerebral I/R injury was TUNEL-positive. Neuronal death and rat mortality rates were greatly inhibited by Nec-1 and 3-MA pre-treatment, but not by Ac-DMQD-CHO. And no activation of caspase-3 was detected after I/R injury. Caspase-8 was expressed richly in GFAP-positive astrocytes and Iba-1-positive microglia, but was not detected in Neun-positive neurons. The nuclear translocation and co-localization of RIP3 and AIF, and their interaction were detected after I/R injury. These processes were inhibited by Nec-1 and 3-MA pre-treatment, but not by Ac-DMQD-CHO. The formation of an RIP3-AIF complex and its nuclear translocation are critical to ischemic neuronal DNA degradation and programmed necrosis. Neurons are more likely to enter the programmed necrosis signal pathway for the loss of caspase-8 suppression.

W4CSeq: Software and Web Application to Analyze 4C-seq Data

Bioinformatics (Oxford, England). Jul, 2016  |  Pubmed ID: 27378289

Circularized Chromosome Conformation Capture followed by deep sequencing (4C-Seq) is a powerful technique to identify genome-wide partners interacting with a pre-specified genomic locus. Here, we present a computational and statistical approach to analyze 4C-Seq data generated from both enzyme digestion and sonication fragmentation-based methods. We implemented a command line software tool and a web interface called w4CSeq, which takes in the raw 4C sequencing data (FASTQ files) as input, performs automated statistical analysis and presents results in a user-friendly manner. Besides providing users with the list of candidate interacting sites/regions, w4CSeq generates figures showing genome-wide distribution of interacting regions, and sketches the enrichment of key features such as TSSs, TTSs, CpG sites and DNA replication timing around 4C sites.

Association of Polymorphisms in Interleukin-8 Gene with Cancer Risk: a Meta-analysis of 22 Case-control Studies

OncoTargets and Therapy. 2016  |  Pubmed ID: 27382310

Interleukin-8 (IL-8) is a kind of chemokine that plays an important role in the development and progression of many human malignancies. Previous studies have uncovered that polymorphisms in IL-8 is associated with the risk of many cancer types, but the results were inconsistent and inconclusive. In the present study, we aimed to explore the roles of IL-8 polymorphisms (rs2227307, rs2227306, +678T/C, rs1126647, and +1633C/T) and cancer risk through a systematic review and meta-analysis. Potential source of heterogeneity was sought out through sensitivity analysis. Desirable data were extracted and registered into databases. Finally, a total of ten publications comprising of 22 case-control studies, including 4,259 cases and 7,006 controls were ultimately eligible for the meta-analysis. No significant association was uncovered for all the five polymorphisms and the overall cancer risk. However, in the stratification analysis by cancer type, a significantly decreased risk of hepatocellular carcinoma was identified for rs2227306 polymorphism (T vs C: odds ratio [OR] =0.721, 95% confidence interval [CI] =0.567-0.916, Pz =0.007; TT vs CC: OR =0.447, 95% CI =0.274-0.728, Pz =0.001; TT vs TC + CC: OR =0.480, 95% CI =0.304-0.760, Pz =0.002). In conclusion, our data shows that rs2227306 polymorphism plays a protective role in hepatocellular carcinoma risk. Future well-designed studies with a larger sample size are warranted to verify our findings.

Isoelectronic Tungsten Doping in Monolayer MoSe2 for Carrier Type Modulation

Advanced Materials (Deerfield Beach, Fla.). Jul, 2016  |  Pubmed ID: 27384240

Carrier type modulation is demonstrated in 2D transition metal dichalcogenides as n-type monolayer MoSe2 is converted to nondegenerate p-type monolayer Mo1- x W x Se2 through isoelectronic doping. Although the alloys are mesoscopically uniform, the p-type conduction in monolayer Mo1- x W x Se2 appears to originate from the upshift of the VBM toward the Fermi level at highly localized "W-rich" regions in the lattice.

Evaluation of the Clinical Significance of Serum Carcinoembryonic Antigen in Patients with Resectable Gastric Adenocarcinoma

Archives of Medical Research. Apr, 2016  |  Pubmed ID: 27387021

Carcinoembryonic antigen (CEA) is the most commonly used tumor marker for gastrointestinal cancers but its value for resectable gastric adenocarcinoma (RGA) patients in areas of high GA incidence is uncertain.

Psychometric Properties of the Autism-Spectrum Quotient in Both Clinical and Non-clinical Samples: Chinese Version for Mainland China

BMC Psychiatry. 2016  |  Pubmed ID: 27388335

The Autism-Spectrum Quotient (AQ) is widely used to quantify autistic traits, which have been evaluated in the parents of individuals with autism spectrum disorders (ASD) and in the general population. This paper's objective was to investigate the AQ's psychometric properties of the Chinese version for mainland China and to establish whether the pattern of sex differences in the quantity of autistic traits exists. We also examined the usefulness of the AQ in differentiating between individuals with ASD, schizophrenia (SCH), obsessive-compulsive disorder (OCD) and healthy controls (HC).

Functional Modification of Fibrous PCL Scaffolds with Fusion Protein VEGF-HGFI Enhanced Cellularization and Vascularization

Advanced Healthcare Materials. Jul, 2016  |  Pubmed ID: 27391702

The lack of efficient vascularization within frequently used poly(ε-caprolactone) (PCL) scaffolds has hindered their application in tissue engineering. Hydrophobin HGFI, an amphiphilic protein, can form a self-assembly layer on the surface of PCL scaffolds and convert their wettability. In this study, a fusion protein consisting of HGFI and vascular endothelial growth factor (VEGF) is prepared by Pichia pastoris expression system. Sodium dodecyl sulface-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting confirm that the VEGF-HGFI is successfully isolated and purified. Transmission electron microscope and water contact angle measurement demonstrate that VEGF-HGFI can form a self-assembly layer with about 25 nm in thickness on electrospun PCL fibers and increase their hydrophilicity. VEGF-HGFI modification can effectively enhance the adhesion, migration, and proliferation of human umbilical vein endothelial cells. Near-infrared fluorescence imaging shows that the VEGF-HGFI modification on PCL scaffolds can exist at least 21 d in vitro and at least 14 d in vivo. Bioluminescence imaging shows that VEGF-HGFI can effectively activate vascular endothelial growth factor receptor 2 receptors. Subcutaneous implantation in mice and rats reveal that cellularization and vascularization are significantly improved in VEGF-HGFI modified PCL scaffolds. These results suggest that VEGF-HGFI is a useful molecule for functional modification of scaffolds to enhance cellularization and vascularization in tissue engineering.

Circulating MicroRNAs and Life Expectancy Among Identical Twins

Annals of Human Genetics. Sep, 2016  |  Pubmed ID: 27402348

Human life expectancy is influenced not only by longevity assurance mechanisms and disease susceptibility loci but also by the environment, gene-environment interactions, and chance. MicroRNAs (miRNAs) are a class of small noncoding RNAs closely related to genes. Circulating miRNAs have been shown as promising noninvasive biomarkers in the development of many pathophysiological conditions. However, the concentration of miRNA in the circulation may also be affected by environmental factors. We used a next-generation sequencing platform to assess the association of circulating miRNA with life expectancy, for which deaths are due to all causes independent of genes. In addition, we showed that miRNAs are present in 41-year archived plasma samples, which may be useful for both life expectancy and all-cause mortality risk assessment. Plasma miRNAs from nine identical male twins were profiled using next-generation sequencing. The average absolute difference in the minimum life expectancy was 9.68 years. Intraclass correlation coefficients were above 0.4 for 50% of miRNAs. Comparing deceased twins with their alive co-twin brothers, the concentrations were increased for 34 but decreased for 30 miRNAs. Identical twins discordant in life expectancy were dissimilar in the majority of miRNAs, suggesting that environmental factors are pivotal in miRNAs related to life expectancy.

Enhanced Plasmonic Nanofocusing of Terahertz Waves in Tapered Graphene Multilayers

Optics Express. Jun, 2016  |  Pubmed ID: 27410629

We investigate the plasmonic nanofocusing of terahertz waves in tapered graphene multilayers separated by dielectrics. The nanofocusing effect is significantly enhanced in the graphene multilayer taper compared with that in a single layer graphene taper due to interlayer coupling between surface plasmon polaritons. The results are optimized by choosing an appropriate layer number of graphene and the field amplitude has been enhanced by 620 folds at λ = 50 μm. Additionally, the structure can slow light to a group velocity ~1/2815 of the light speed in vacuum. Our study provides a unique approach to compress terahertz waves into deep subwavelength scale and may find great applications in terahertz nanodevices for imaging, detecting and spectroscopy.

New Paradigms for Understanding and Step Changes in Treating Active and Chronic, Persistent Apicomplexan Infections

Scientific Reports. 2016  |  Pubmed ID: 27412848

Toxoplasma gondii, the most common parasitic infection of human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we develop novel models to facilitate drug development: EGS strain T. gondii forms cysts in vitro that induce oocysts in cats, the gold standard criterion for cysts. These cysts highly express cytochrome b. Using these models, we envisioned, and then created, novel 4-(1H)-quinolone scaffolds that target the cytochrome bc1 complex Qi site, of which, a substituted 5,6,7,8-tetrahydroquinolin-4-one inhibits active infection (IC50, 30 nM) and cysts (IC50, 4 μM) in vitro, and in vivo (25 mg/kg), and drug resistant Plasmodium falciparum (IC50, <30 nM), with clinically relevant synergy. Mutant yeast and co-crystallographic studies demonstrate binding to the bc1 complex Qi site. Our results have direct impact on improving outcomes for those with toxoplasmosis, malaria, and ~2 billion persons chronically infected with encysted bradyzoites.

Tailoring Vacancies Far Beyond Intrinsic Levels Changes the Carrier Type and Optical Response in Monolayer MoSe2-x Crystals

Nano Letters. Aug, 2016  |  Pubmed ID: 27416103

Defect engineering has been a critical step in controlling the transport characteristics of electronic devices, and the ability to create, tune, and annihilate defects is essential to enable the range of next-generation devices. Whereas defect formation has been well-demonstrated in three-dimensional semiconductors, similar exploration of the heterogeneity in atomically thin two-dimensional semiconductors and the link between their atomic structures, defects, and properties has not yet been extensively studied. Here, we demonstrate the growth of MoSe2-x single crystals with selenium (Se) vacancies far beyond intrinsic levels, up to ∼20%, that exhibit a remarkable transition in electrical transport properties from n- to p-type character with increasing Se vacancy concentration. A new defect-activated phonon band at ∼250 cm(-1) appears, and the A1g Raman characteristic mode at 240 cm(-1) softens toward ∼230 cm(-1) which serves as a fingerprint of vacancy concentration in the crystals. We show that post-selenization using pulsed laser evaporated Se atoms can repair Se-vacant sites to nearly recover the properties of the pristine crystals. First-principles calculations reveal the underlying mechanisms for the corresponding vacancy-induced electrical and optical transitions.

Further Correction: Low Bandgap Semiconducting Polymers for Polymeric Photovoltaics

Chemical Society Reviews. Aug, 2016  |  Pubmed ID: 27420563

Further correction for 'Low bandgap semiconducting polymers for polymeric photovoltaics' by Chang Liu et al., Chem. Soc. Rev., 2016, DOI: 10.1039/c5cs00650c.

Forsythiae Fructus Inhibits B16 Melanoma Growth Involving MAPKs/Nrf2/HO-1 Mediated Anti-Oxidation and Anti-Inflammation

The American Journal of Chinese Medicine. 2016  |  Pubmed ID: 27430915

Forsythiae Fructus, the fruits of Forsythia suspensa (Thunb.) Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine (TCM). It is a typical heat-clearing and detoxicating herb, according to TCM theory. In this study, we investigated the antitumor effect of Forsythiae Fructus aqueous extract (FAE) on B16-F10 melanoma cells in vivo. The transplanted B16-F10 melanoma in C57BL/6 mice was established and used for the evaluation of the in vivo antitumor effect of FAE. FAE strongly inhibited the growth of B16-F10 cells in vitro and the tumor in vivo. The survival time of tumor-bearing mice was significantly prolonged by FAE. FAE inhibited cancer cell proliferation and angiogenesis in the tumor, as indicated by the decreased expressions of Ki67 and CD31. The levels of ROS, MDA, TNF-[Formula: see text] and IL-6 decreased, while GSH increased in the FAE treatment group, indicating FAE possesses strong anti-oxidative and anti-inflammatory activity. The expression of anti-oxidant proteins Nrf-2 and HO-1, tumor suppressors P53 and p-PTEN, and the MAPK pathways in tumor tissues were upregulated by FAE treatment. These data demonstrated that FAE exhibited strong antitumor activity against B16-F10 murine melanoma both in vitro and in vivo. The antitumor effect of FAE involved decreases in oxidative stress and inflammation in the tumor, which is closely related to the heat-clearing and detoxicating properties of FAE.

Anti‑migratory Effect of Rapamycin Impairs Allograft Imaging by 18F‑fluorodeoxyglucose‑labeled Splenocytes

Molecular Medicine Reports. Sep, 2016  |  Pubmed ID: 27432554

Tracking lymphocyte migration is an emerging strategy for non‑invasive nuclear imaging of allografts; however, its clinical application remains to be fully demonstrated. In the present study, the feasibility of using rapamycin‑treated 18F‑fluorodeoxyglucose (18F‑FDG)‑labeled splenocytes for the in vivo imaging of allografts was evaluated. C57BL/6 skin was heterotopically transplanted onto non‑obese diabetic/severe combined immunodeficient recipient mice. BALB/c 18F‑FDG‑labeled splenocytes with or without rapamycin pretreatment (designated as FR and FC cells, respectively) were transferred into recipient mice 30 days later. Imaging of radiolabeled cells in the skin grafts was conducted through in vivo dynamic whole‑body phosphor‑autoradiography and histological analysis. Notably, rapamycin impaired the migration of 18F‑FDG‑labeled splenocytes to the graft. At all time points, the radioactivity of allografts (digital light units/mm2) was significantly lower in the group that received FR cells, compared with the group that received FC cells (P<0.01). Furthermore, the peak allograft to native skin ratio was 1.29±0.02 at 60 min for the FR group and 3.29±0.17 at 30 min for the FC group (P<0.001). In addition, the in vivo radioactivity of the allografts was observed to be correlated with the transferred cells, which were observed histologically (r2=0.887; P<0.0001). Although 18F‑FDG‑labeled splenocytes migrated to the allograft, imaging of these cells may not be possible in the presence of rapamycin.

Effects of Chinese Propolis in Protecting Bovine Mammary Epithelial Cells Against Mastitis Pathogens-Induced Cell Damage

Mediators of Inflammation. 2016  |  Pubmed ID: 27433029

Chinese propolis (CP), an important hive product, can alleviate inflammatory responses. However, little is known regarding the potential of propolis treatment for mastitis control. To investigate the anti-inflammatory effects of CP on bovine mammary epithelial cells (MAC-T), we used a range of pathogens to induce cellular inflammatory damage. Cell viability was determined and expressions of inflammatory/antioxidant genes were measured. Using a cell-based reporter assay system, we evaluated CP and its primary constituents on the NF-κB and Nrf2-ARE transcription activation. MAC-T cells treated with bacterial endotoxin (lipopolysaccharide, LPS), heat-inactivated Escherichia coli, and Staphylococcus aureus exhibited significant decreases in cell viability while TNF-α and lipoteichoic acid (LTA) did not. Pretreatment with CP prevented losses in cell viability associated with the addition of killed bacteria or bacterial endotoxins. There were also corresponding decreases in expressions of proinflammatory IL-6 and TNF-α mRNA. Compared with the mastitis challenged cells, enhanced expressions of antioxidant genes HO-1, Txnrd-1, and GCLM were observed in CP-treated cells. CP and its polyphenolic active components (primarily caffeic acid phenethyl ester and quercetin) had strong inhibitive effects against NF-κB activation and increased the transcriptional activity of Nrf2-ARE. These findings suggest that propolis may be valuable in the control of bovine mastitis.

Separation and Purification of Astaxanthin from Phaffia Rhodozyma by Preparative High-speed Counter-current Chromatography

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. Sep, 2016  |  Pubmed ID: 27433984

An effective high-speed counter-current chromatography (HSCCC) method was established for the preparative isolation and purification of astaxanthin from Phaffia rhodozyma. With a two-phase solvent system composed of n-hexane-acetone-ethanol-water (1:1:1:1, v/v/v/v), 100mg crude extract of P. rhodozyma was separated to yield 20.6mg of astaxanthin at 92.0% purity. By further one step silica gel column chromatography, the purity reached 99.0%. The chemical structure of astaxanthin was confirmed by thin layer chromatography (TLC), UV spectroscopy scanning, high performance liquid chromatography with a ZORBAX SB-C18 column and a Waters Nova-pak C18 column, and ESI/MS/MS.

Differences in Factors Affecting Various Crash Types with High Numbers of Fatalities and Injuries in China

PloS One. 2016  |  Pubmed ID: 27439113

Road traffic crashes that involve very high numbers of fatalities and injuries arouse public concern wherever they occur. In China, there are two categories of such crashes: a crash that results in 10-30 fatalities, 50-100 serious injuries or a total cost of 50-100 million RMB ($US8-16m) is a "serious road traffic crash" (SRTC), while a crash that is even more severe or costly is a "particularly serious road traffic crash" (PSRTC). The aim of this study is to identify the main factors affecting different types of these crashes (single-vehicle, head-on, rear-end and side impact) with the ultimate goal of informing prevention activities and policies.

Phylogeography of Libanotis Buchtormensis (Umbelliferae) in Disjunct Populations Along the Deserts in Northwest China

PloS One. 2016  |  Pubmed ID: 27442136

In Northwest China, aridification and desert expansion play significant roles in promoting desert plant diversification and speciation. However, to date, little is known about the effects of the desert barrier on the population structure of montane, non-desert species in the area. In this study, we sequenced chloroplast DNA regions (trnL-trnF and trnS-trnG) and a nuclear gene (rpb2) to investigate the population differentiation and phylogeographical history of Libanotis buchtormensis, a perennial montane species possessing a disjunct distribution at the periphery of the central desert. In total, 23 chloroplast haplotypes and 24 nuclear haplotypes were recovered from the 21 natural populations and six hebarium specimens. Phylogenetic analysis based on the combined plastid and nuclear dataset revealed two distinct lineages of L. buchtormensis, which inhabit the disjunct areas on both sides of the desert zone. The molecular dating analysis indicated that the divergence between the southeastern and the northwestern populations occurred in the middle Pleistocene, concomitantly with the desert expansion. The geographical vicariance likely contributed to the present disjunct distribution of L. buchtormensis across the deserts in Northwest China. Populations in the southeastern region may have migrated from the northwestern region, and seem to be a peripheral distribution of L. buchtormensis.

High Promoter Methylation Levels of Glutathione-S-transferase M3 Predict Poor Prognosis of Acute-on-chronic Hepatitis B Liver Failure

Hepatology Research : the Official Journal of the Japan Society of Hepatology. Jul, 2016  |  Pubmed ID: 27442719

This study aimed to evaluate the prognostic value of glutathione-S-transferase M3 (GSTM3) gene promoter methylation in patients with acute-on-chronic hepatitis B liver failure (ACHBLF).

A Facile and General Strategy for the Synthesis of Porous Flowerlike Pt-based Nanocrystals As Effective Electrocatalysts for Alcohol Oxidation

Nanoscale. Aug, 2016  |  Pubmed ID: 27443246

In this paper, porous flowerlike Pt-based (Pt, PdPt, RhPt and RhPdPt) nanocrystals were successfully achieved by a simple, economic, environmentally friendly route under the same synthetic conditions at 85 °C. The electrocatalytic properties of these flowerlike Pt-based nanocrystals toward alcohols (glycol, glycerol, methanol and ethanol) oxidation were investigated and they displayed enhanced catalytic performance compared with commercial Pt black. Among them, porous Pd45.5Pt54.5 nanoflowers showed the best catalytic performance with significant mass activity and long-term stability. More importantly, the current synthesis strategy can be easily amplified to gram-scale production.

Role of CD133(+) Cells in Tongue Squamous Carcinomas: Characteristics of 'stemness' in Vivo and in Vitro

Oncology Letters. Aug, 2016  |  Pubmed ID: 27446361

The objective of the present study was to determine the 'stemness' characteristics of CD133(+) cells (harvested from the squamous cell tongue carcinoma Tca-8113 cell line) in vitro and to observe the tumourigenicity of the CD133(+) cells in the bodies of NOD/SCID mice. Single cells from the Tca-8113 cell line were observed for multiplication capacity in vitro. The suspending and pelletizing phenomena of Tca-8113 cells in vitro were also observed, and the expression of CD133 in squamous cell carcinoma of the tongue was measured. The CD133(+) cells from the Tca-8113 cell line were purified, and their multiplication capacity and differentiation potency were observed. The NOD/SCID mouse model was established, and the tumourigenicity of the CD133(+) cells was determined. The Tca-8113 cells were observed to emerge in the form of suspending tumour spheres in squamous cell carcinoma of the tongue. Monoplasts with sustainable multiplication capacity accounted for ~5.32% of the spheres, and 0.95% of the CD133(+) cells were expressed in squamous cell carcinoma of the tongue, with stronger multiplication capacity and differentiation potency in vitro. Stronger tumourigenicity was also observed in the bodies of the NOD/SCID mice. CD133(-) cells exhibited a multiplication capacity to a certain extent. Overall, the CD133(+) cells in squamous cell carcinoma of the tongue are characterised by relatively strong tumourigenicity capacity in vivo and in vitro. To a certain extent, these CD133(+) cells demonstrate the characteristics of 'stemness'.

Abnormal Glucose Tolerance in Infants and Young Children with Cystic Fibrosis

American Journal of Respiratory and Critical Care Medicine. Jul, 2016  |  Pubmed ID: 27447840

In cystic fibrosis, abnormal glucose tolerance is associated with decreased lung function and worsened outcomes. Translational evidence indicates that abnormal glucose tolerance may begin in early life.

Successional Trajectories of Bacterioplankton Community over the Complete Cycle of a Sudden Phytoplankton Bloom in the Xiangshan Bay, East China Sea

Environmental Pollution (Barking, Essex : 1987). Jul, 2016  |  Pubmed ID: 27453358

Phytoplankton bloom has imposed ecological concerns worldwide; however, few studies have been focused on the successional trajectories of bacterioplankton community over a complete phytoplankton bloom cycle. Using 16S pyrosequencing, we investigated how the coastal bacterioplankton community compositions (BCCs) respond to a phytoplankton bloom in the Xiangshan Bay, East China Sea. The results showed that BCCs were significantly different among the pre-bloom, bloom, and after-bloom stages, with the lowest bacterial diversity at the bloom phase. The BCCs at the short-term after-bloom phase showed a rapid but incomplete recovery to the pre-bloom phase, evidenced by 69.8% similarity between pre-bloom and after-bloom communities. This recovery was parallel with the dynamics of the operational taxonomic units (OTUs) affiliated with Actinobacteria, Bacteroidetes, Cyanobacteria, Alphaproteobacteria and Gammaproteobacteria, whose abundance enriched when bloom occur, and decreased after-bloom, and vice versa. Collectively, the results showed that the BCCs were sensitive to algal-induced disturbances, but could recover to a certain extent after bloom. In addition, OTUs which enriched or decreased during this process are closely associated with this temporal pattern, thus holding the potential to evaluate and indicate the succession stage of phytoplankton bloom.

A Redox-sensitive, Oligopeptide-guided, Self-assembling, and Efficiency-enhanced (ROSE) System for Functional Delivery of MicroRNA Therapeutics for Treatment of Hepatocellular Carcinoma

Biomaterials. Oct, 2016  |  Pubmed ID: 27459325

Lack of efficient adjuvant therapy contributes to a high incidence of recurrence and metastasis of hepatocellular carcinoma (HCC). A novel therapeutic is required for adjuvant treatment of HCC. We developed a polymer-based nanosystem (ROSE) for functional gene therapy by synthesizing a supramolecular complex self-assembled from polycations and functional adamantyl modules. The ROSE system condensing tumor suppressor microRNA-34a (miR-34a) therapeutics becomes ROSE/miR-34a nanoparticles that could facilitate gene transfection in HCC cells with satisfied stability and efficiency, possibly due to proton sponge effect by polycations, PEGlyation protection, and controlled release by breakdown of disulfide bonds. Meanwhile, modification with a targeting oligopeptide SP94 in ROSE/miR-34a enables approximately higher affinity for LM3 HCC cells than hepatocytes in vitro and greater HCC specificity in vivo. Furthermore, ROSE/miR-34a nanoparticles significantly inhibits HCC cell proliferation and in vivo tumor growth, representing a notable effect improvement over conventional gene delivery strategies. ROSE/miR-34a, featuring redox-responsiveness, oligopeptide-guided specificity, self-assembly, and enhanced transfection, is therefore a potential therapeutic agent in future adjuvant therapy for HCC treatment.

Vector Plasmonic Lattice Solitons in Nonlinear Graphene-pair Arrays

Optics Letters. Aug, 2016  |  Pubmed ID: 27472633

We investigate the vector plasmonic lattice solitons (PLSs) in nonlinear graphene-pair arrays (GPAs) consisting of periodically arranged double graphene sheets, which are spatially separated. There are two dispersion bands for the Bloch modes in the array due to the coupling of surface plasmon polaritons (SPPs) between the graphene pairs. The vector PLSs composed of two components originate from the nonlinear interaction of Bloch modes in different bands. Both components undergo mutual self-trapping through the balance between diffraction and self-focusing nonlinearity of graphene. Thanks to the strong confinement of SPPs, the vector PLSs can be squeezed into a lateral width of ∼λ/100. The study provides a promising approach to all-optical control on a deep-subwavelength scale.

Corrigendum to 'Ca(2+)/calmodulin-dependent Protein Kinase IIγ, a Critical Mediator of the NF-κB Network, is a Novel Therapeutic Target in Non-small Cell Lung Cancer' [Cancer Lett. 344 (1), 119-128; March 1, 2014]

Cancer Letters. Oct, 2016  |  Pubmed ID: 27491000

Growth of Epitaxial Oxide Thin Films on Graphene

Scientific Reports. 2016  |  Pubmed ID: 27515496

The transfer process of graphene onto the surface of oxide substrates is well known. However, for many devices, we require high quality oxide thin films on the surface of graphene. This step is not understood. It is not clear why the oxide should adopt the epitaxy of the underlying oxide layer when it is deposited on graphene where there is no lattice match. To date there has been no explanation or suggestion of mechanisms which clarify this step. Here we show a mechanism, supported by first principles simulation and structural characterisation results, for the growth of oxide thin films on graphene. We describe the growth of epitaxial SrTiO3 (STO) thin films on a graphene and show that local defects in the graphene layer (e.g. grain boundaries) act as bridge-pillar spots that enable the epitaxial growth of STO thin films on the surface of the graphene layer. This study, and in particular the suggestion of a mechanism for epitaxial growth of oxides on graphene, offers new directions to exploit the development of oxide/graphene multilayer structures and devices.

A Dynamic Model of Human and Livestock Tuberculosis Spread and Control in Urumqi, Xinjiang, China

Computational and Mathematical Methods in Medicine. 2016  |  Pubmed ID: 27525034

We establish a dynamical model for tuberculosis of humans and cows. For the model, we firstly give the basic reproduction number R 0. Furthermore, we discuss the dynamical behaviors of the model. By epidemiological investigation of tuberculosis among humans and livestock from 2007 to 2014 in Urumqi, Xinjiang, China, we estimate the parameters of the model and study the transmission trend of the disease in Urumqi, Xinjiang, China. The reproduction number in Urumqi for the model is estimated to be 0.1811 (95% confidence interval: 0.123-0.281). Finally, we perform some sensitivity analysis of several model parameters and give some useful comments on controlling the transmission of tuberculosis.

XAV939 Inhibits Intima Formation by Decreasing VSMC Proliferation and Migration Through Blocking Wnt Signaling

Journal of Cardiovascular Pharmacology. Aug, 2016  |  Pubmed ID: 27525574

Excessive proliferation, migration and oxidative stress of vascular smooth muscle cells (VSMCs) are key mechanisms involved in intima formation, which is the basic pathological process of in stent restenosis. This study aims at exploring the role of XAV939 in proliferation, migration and ROS generation of VSMCs and hence evaluating its effects on intima formation.

Adhesion-based Tumor Cell Capture Using Nanotopography

Colloids and Surfaces. B, Biointerfaces. Aug, 2016  |  Pubmed ID: 27526289

Circulating tumor cells (CTCs) shed from primary tumors, transport through the blood stream to distant sites, and cause 90% of cancer deaths. Although different techniques have been developed to isolate CTCs for cancer detection, diagnosis and treatment, the heterogeneity of expression of the target antigen and the significant size variance in CTCs limit clinical applications of antibody- and size-based isolation techniques. Cell adhesion using nanotopography has been suggested as a promising approach to isolate CTCs independent of surface marker expression or size of CTCs. However, the nanotopographies studied are mainly nanopillars; the influence of other nanotopography such as nanogratings and their dimensions on tumor cell capture remains to be investigated. This study examined capture performance of several cancer cell lines of different types, surface marker expression and metastatic status on nanotopographies of various geometries and dimensions without antibody conjugation. The cancer cells exhibited differential capture performance on the nanotopographies with an efficiency up to 52%. Compared with flat surfaces and isotropic, discrete nanopillars, nanogratings favored cancer cell adhesion, thus improving the capture efficiency. The influence of nanotopography height studied, on the other hand, was less significant. This study provides useful information to optimize nanotopography for further improvement of CTC capture efficiency.

Penguins Reduced Olfactory Receptor Genes Common to Other Waterbirds

Scientific Reports. 2016  |  Pubmed ID: 27527385

The sense of smell, or olfaction, is fundamental in the life of animals. However, penguins (Aves: Sphenisciformes) possess relatively small olfactory bulbs compared with most other waterbirds such as Procellariiformes and Gaviiformes. To test whether penguins have a reduced reliance on olfaction, we analyzed the draft genome sequences of the two penguins, which diverged at the origin of the order Sphenisciformes; we also examined six closely related species with available genomes, and identified 29 one-to-one orthologous olfactory receptor genes (i.e. ORs) that are putatively functionally conserved and important across the eight birds. To survey the 29 one-to-one orthologous ORs in penguins and their relatives, we newly generated 34 sequences that are missing from the draft genomes. Through the analysis of totaling 378 OR sequences, we found that, of these functionally important ORs common to other waterbirds, penguins have a significantly greater percentage of OR pseudogenes than other waterbirds, suggesting a reduction of olfactory capability. The penguin-specific reduction of olfactory capability arose in the common ancestor of penguins between 23 and 60 Ma, which may have resulted from the aquatic specializations for underwater vision. Our study provides genetic evidence for a possible reduction of reliance on olfaction in penguins.

Sorting Protein Decoys by Machine-learning-to-rank

Scientific Reports. 2016  |  Pubmed ID: 27530967

Much progress has been made in Protein structure prediction during the last few decades. As the predicted models can span a broad range of accuracy spectrum, the accuracy of quality estimation becomes one of the key elements of successful protein structure prediction. Over the past years, a number of methods have been developed to address this issue, and these methods could be roughly divided into three categories: the single-model methods, clustering-based methods and quasi single-model methods. In this study, we develop a single-model method MQAPRank based on the learning-to-rank algorithm firstly, and then implement a quasi single-model method Quasi-MQAPRank. The proposed methods are benchmarked on the 3DRobot and CASP11 dataset. The five-fold cross-validation on the 3DRobot dataset shows the proposed single model method outperforms other methods whose outputs are taken as features of the proposed method, and the quasi single-model method can further enhance the performance. On the CASP11 dataset, the proposed methods also perform well compared with other leading methods in corresponding categories. In particular, the Quasi-MQAPRank method achieves a considerable performance on the CASP11 Best150 dataset.

Additive Effects of the Risk Alleles of PNPLA3 and TM6SF2 on Non-alcoholic Fatty Liver Disease (NAFLD) in a Chinese Population

Frontiers in Genetics. 2016  |  Pubmed ID: 27532011

Recent genome-wide association studies have identified that variants in or near PNPLA3, NCAN, GCKR, LYPLAL1, and TM6SF2 are significantly associated with non-alcoholic fatty liver disease (NAFLD) in multiple ethnic groups. Studies on their impact on NAFLD in Han Chinese are still limited. In this study, we examined the relevance of these variants to NAFLD in a community-based Han Chinese population and further explored their potential joint effect on NAFLD. Six single nucleotide polymorphisms (SNPs) (PNPLA3 rs738409, rs2294918, NCAN rs2228603, GCKR rs780094, LYPLAL1 rs12137855, and TM6SF2 rs58542926) previously identified in genome-wide analyses, to be associated with NAFLD were genotyped in 384 NAFLD patients and 384 age- and gender-matched healthy controls. We found two out of the six polymorphisms, PNPLA3 rs738409 (OR = 1.52, 95%CI: 1.19-1.96; P = 0.00087) and TM6SF2 rs58542926 (OR = 2.11, 95%CI: 1.34-3.39; P = 0.0016) are independently associated with NAFLD after adjustment for the effects of age, gender, and BMI. Our analysis further demonstrated the strong additive effects of the risk alleles of PNPLA3 and TM6SF2 with an overall significance between the number of risk alleles and NAFLD (OR = 1.64, 95%CI: 1.34-2.01; P = 1.4 × 10(-6)). The OR for NAFLD increased in an additive manner, with an average increase in OR of 1.52 per additional risk allele. Our results confirmed that the PNPLA3 and TM6SF2 variants were the most significant risk alleles for NAFLD in Chinese population. Therefore, genotyping these two genetic risk factors may help identify individuals with the highest risk of NAFLD.

Double Primary Hepatic Cancer (hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma) Originating from Hepatic Progenitor Cell: a Case Report and Review of the Literature

World Journal of Surgical Oncology. 2016  |  Pubmed ID: 27535234

Synchronous development of primary hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in different sites of the liver have rarely been reported before. The purpose of this study is to investigate the clinicopathological characteristics of synchronous double cancer of HCC and ICC.

Differences in the Performance of PCL-based Vascular Grafts As Abdominal Aorta Substitutes in Healthy and Diabetic Rats

Biomaterials Science. Aug, 2016  |  Pubmed ID: 27537499

Great progress has been made in the field of vascular tissue engineering, with some artificial vascular grafts already exhibiting promising outcomes in animal models. However, these studies were mostly conducted using healthy animals, which are not representative of actual clinical demands. Indeed, patients who require artificial vascular graft implantation are often accompanied by other comorbidities, such as hyperlipidaemia, hypertension and diabetes which should also be taken into consideration when assessing the potential of vascular grafts that are intended for clinical applications. In the present study, we established a rat model with type 2 diabetes (T2D) for performance evaluation of an electrospun PCL vascular graft. Our data showed that rats with T2D had elevated incidents of adverse event rates, including exacerbated platelet adhesion, inflammation, early calcification and impaired regeneration compared to the non-diabetic controls. Thus, we report that T2D exacerbates the regeneration process after in vivo implantation of vascular grafts. More advanced grafts are in demand for clinical use in patients with clinical complications such as T2D.

Association of Patatin-like Phospholipase Domain-containing Protein 3 Gene Polymorphisms with Susceptibility of Nonalcoholic Fatty Liver Disease in a Han Chinese Population

Medicine. Aug, 2016  |  Pubmed ID: 27537584

Gene polymorphisms had been found to be associated with increased risk of nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to assess the association between rs2896019 and rs3810622 in PNPLA3 with the susceptibility to NAFLD in Han Chinese population.A total of 384 NAFLD patients and 384 controls were enrolled in the study. Blood samples collected from each subject were used for biochemical index analysis and DNA extraction. Genotyping analyses of PNPLA3 rs2896019 and rs3810622 were performed by real-time PCR methods.Results showed that patients with genotype GG of rs2896019 had a higher incidence of NAFLD than patients with genotypes GT and TT (62.4% vs 52.0% and 43.3%, respectively, P = 0.002), and a higher risk of moderate to severe NAFLD than patients with genotypes GT and TT (60.3% vs 46.2% and 40.2%, respectively, P = 0.03). Furthermore, patients with genotype GG of rs2896019 had higher levels of low-density lipoprotein (LDL, P < 0.001), ALT (P = 0.003), and AST (P = 0.002). Patients with genotype TT of rs3810622 had a higher incidence of NAFLD than patients with genotypes CT and CC (56.7% vs 48.4% and 41.5%, respectively, P = 0.013). Likewise, patients with genotype TT of rs3810622 had higher levels of ALT (P = 0.021) and blood glucose (GLU) (P = 0.034). Haplotype association analysis showed that GT haplotype conferred a statistically significant increased risk for NAFLD (OR = 1.49; 95% CI = 1.20-1.84, P < 0.01).These results suggest that PNPLA3 rs2896019 and rs3810622 polymorphisms significantly contribute to increased NAFLD risk in Han Chinese population.

Rapid Proliferationand Nucleolar Organizer Targeting Centromeric Retrotransposonsin Cotton

The Plant Journal : for Cell and Molecular Biology. Aug, 2016  |  Pubmed ID: 27539015

Centromeric chromatin in most eukaryotes is composed of highly repetitive centromeric retrotransposons and satellite repeats that are highly variable even among closely related species.The evolutionary mechanisms that underlie the rapid evolution of centromeric repeatsremain unknown. To obtain insight into the evolution of centromeric repeats following polyploidy, we studied a model diploid progenitor (Gossypium raimondii,D-genome) of the allopolyploid (AD-genome) cottons, G. hirsutum and G. barbadense. Sequence analysis of chromatin-immunoprecipitated DNA showed that the G. raimondii centromeric repeats originated from retrotransposon-related sequences. Comparative analysis showed that nine of the ten analyzed centromeric repeats were absent from the centromeres in the A-genome and related diploid species (B-, F- and G-genome), indicating that they colonized the centromeres of D-genome lineage after the divergence of the A- and D- ancestral species or that they were ancestrally retained prior to the origin of Gossypium. Notably, six of the nine repeats were present in both the A- and D-subgenomes in tetraploid G. hirsutum, and increased in abundance in both subgenomes. This suggeststhat centromeric repeats may spread and proliferate between genomes subsequent to polyploidization. Two repeats, Gr334 and Gr359 occurred in both the centromeres and nucleolar organizer regions (NORs) in D and AD genome species, yet localized to just the NORs in A-, B-, F-, and G-genome species. Contained within is a story of an established centromeric repeat that is eliminated and allopolyploidization provides an opportunity for reinvasion and reestablishment, which broadens our evolutionary understanding behind the cycles of centromeric repeat establishment and targeting. This article is protected by copyright. All rights reserved.

IDH1/2 Mutants Inhibit TET-Promoted Oxidation of RNA 5mC to 5hmC

PloS One. 2016  |  Pubmed ID: 27548812

TETs (TET1/2/3) play critical roles in multi cellular processes through DNA demethylation driven by oxidation of DNA 5mdC to 5hmdC. Interestingly, recent studies indicated that TETs also oxidate RNA 5mC to 5hmC. However, little is known about the distribution of RNA 5hmC and the regulatory mechanism of RNA 5hmC in human. Here, we show that 5hmC is enriched in mRNA, and IDH1/2 mutants inhibit TET-promoted oxidation of RNA 5mC to 5hmC. Since IDH1/2 mutations have been described to block the DNA oxidative activity of TETs, we hypothesized that IDH1/2 mutations might also inhibit the RNA oxidative activity of TETs. To evaluate the role of IDH1/2 mutations in RNA 5hmC, TETs with/without IDH1/2 mutants were overexpressed in human HEK293 cells. Resultant DNA and RNA were digested and analyzed by triple-quadrupole LC mass spectrometer. DNA 5hmdC and RNA 5hmC modifications were quantified with external calibration curves of appropriate standards. It was found that compared with total RNA (5hmC/C: less than 2 X 10-7), mRNA showed much higher 5hmC level (5hmC/C: ∼7 X 10-6). Further study indicated that IDH1/2 mutants showed significant ability to inhibit TET-promoted RNA5hmC. Consistent with this result, overexpression of IDH1/2 mutants also inhibited TET catalytic domain-promoted oxidation of RNA. In this study, we show not only the enrichment of 5hmC in mRNA, but also a regulatory mechanism of RNA 5hmC-IDH1/2 mutations inhibit TET-promoted RNA 5hmC, which suggests an involvement of IDH1/2 mutations in tumorigenesis through the deregulation of RNA biology.

Structure and Digestion of Hybrid Indica Rice Starch and Its Biosynthesis

International Journal of Biological Macromolecules. Aug, 2016  |  Pubmed ID: 27554933

The fine structure (including contents, size and chains length distribution) of amylose and amylopectin of Hybrid Indica Rice starch have an impact on digestion properties of Indica Rice. Indica Rice starches with different amylose contents were chosen as model materials in this study. The amylose and amylopectin size were characterized using size-exclusion chromatography (SEC), the fine structure of amylopectin were studied by flurophore-assisted carbohydrate electrophoresis (FACE) and parameterized by amylopectin biosynthesis model to identify associations with starch digestibility. The digestograms of all starches fit first-order kinetics. All results show that the hybrid Indica rice starch with higher amylose content has a slower digestion rate. SEC results show that there is no obviously in chains length distribution (CLD) for amylopectin, but a significantly sharp difference in amylose. No difference in amylopectin was also observed from FACE result. The amylose starch controlled by GBSSI enzyme may be the key parameter to influence starch digestion.

Construction of Epidermal Growth Factor Receptor Peptide Magnetic Nanovesicles with Lipid Bilayers for Enhanced Capture of Liver Cancer Circulating Tumor Cells

Analytical Chemistry. Aug, 2016  |  Pubmed ID: 27558867

Highly effective targeted tumor recognition via vectors is crucial for cancer detection. In contrast to antibodies and proteins, peptides are direct targeting ligands with a low molecular weight. In the present study, a peptide magnetic nanovector platform containing a lipid bilayer was designed using a peptide amphiphile (PA) as a skeleton material in a controlled manner without surface modification. Fluorescein isothiocyanate-labeled epidermal growth factor receptor (EGFR) peptide nanoparticles (NPs) could specifically bind to EGFR-positive liver tumor cells. EGFR peptide magnetic vesicles (EPMVs) could efficiently recognize and separate hepatoma carcinoma cells from cell solutions and treated blood samples (ratio of magnetic EPMVs versus anti-EpCAM NPs: 3.5 ± 0.29). Analysis of the circulating tumor cell (CTC) count in blood samples from 32 patients with liver cancer showed that EPMVs could be effectively applied for CTC capture. Thus, this nanoscale, targeted cargo-packaging technology may be useful for designing cancer diagnostic systems.

Macrophages As Active Nanocarriers for Targeted Early and Adjuvant Cancer Chemotherapy

Small (Weinheim an Der Bergstrasse, Germany). Aug, 2016  |  Pubmed ID: 27560388

Taking advantage of the highly permeable vasculature and lack of lymphatic drainage in solid tumors (EPR effect), nanosized drug delivery systems or nanomedicines have been extensively explored for tumor-targeted drug delivery. However, in most clinical cases tumors such as the early stage tumors and post-surgery microscopic residual tumors have not yet developed such pathological EPR features, i.e., EPR-deficient. Therefore, nanomedicines may not be applicable for such these tumors. Macrophages by nature can actively home and extravasate through the tight vascular wall into tumors and migrate to their hypoxic regions, and possess perfect stealth ability for long blood circulation and impressive phagocytosis for drug loadings. Thus, nanomedicines loaded in macrophages would harness both merits and gain the active tumor homing capability independent of the EPR effect for treatments of the EPR-deficient tumors. Herein, the critical considerations, current progress, challenges and future prospects of macrophages as carriers for nanomedicines are summarized, aiming at rational design of EPR-independent tumor-targeting active nanomedicines for targeted early and adjuvant cancer chemotherapy.

Moral Judgment in Patients with Idiopathic Generalized Epilepsy

Seizure. Aug, 2016  |  Pubmed ID: 27567267

The aim of the current study was to investigate morality while also investigating frontal lobe function with the goal of studying the relationship between frontal lobe and morality in patients with idiopathic generalized epilepsy.

Identification of Blood Protein Biomarkers of Acute Liver Injury by Targeted Quantitative Proteomics in Acetaminophen and Carbon Tetrachloride Treated Mouse Models and Acetaminophen Overdose Patients

Journal of Proteome Research. Aug, 2016  |  Pubmed ID: 27575953

Organ-enriched blood proteins, those produced primarily in one organ and secreted or exported to the blood, potentially afford a powerful and specific approach to assessing diseases in their cognate organs. In this paper, we demonstrate that quantification of organ-enriched proteins in the blood offers a new strategy to find biomarkers for diagnosis and assessment of drug-induced liver injury (and presumably the assessment of other liver diseases). We used selected reaction monitoring (SRM) mass spectrometry to quantify 81 liver-enriched proteins plus three aminotransferases (ALT1, AST1, and AST2) in plasma of C57BL/6J and NOD/ShiLtJ mice exposed to acetaminophen or carbon tetrachloride. Plasma concentrations of 49 liver-enriched proteins were perturbed significantly in response to liver injury induced by one or both toxins. We validated four of these toxin-responsive proteins (ALDOB, ASS1, BHMT and GLUD1) by Western blotting. By both assays, these four proteins constitute liver injury markers superior to currently employed markers such as ALT and AST. A similar approach was also successful in human serum where we had analyzed 66 liver-enriched proteins in acetaminophen overdose patients. Of these, 23 proteins were elevated in patients; 15 of 23 overlapped with the concentration-increased proteins in the mouse study. A combination of 5 human proteins, AGXT, ALDOB, CRP, FBP1, and MMP9, provides the best diagnostic performance to distinguish acetaminophen overdose patients from controls (sensitivity: 0.85, specificity: 0.84, accuracy: 85%). These five blood proteins are candidates for detecting acetaminophen-induced liver injury using next-generation diagnostic devices (e.g, microfluidic ELIZA assays).

Beneficial Effects of Renal Denervation on Cardiac Angiogenesis in Rats with Prolonged Pressure Overload

Acta Physiologica (Oxford, England). Aug, 2016  |  Pubmed ID: 27575955

Renal denervation (RDN) has beneficial effects on cardiac remodeling and function in resistant hypertension. We aimed to investigate the impact of RDN on cardiac angiogenesis during prolonged pressure overload.

Li-ion Battery Separators, Mechanical Integrity and Failure Mechanisms Leading to Soft and Hard Internal Shorts

Scientific Reports. 2016  |  Pubmed ID: 27581185

Separator integrity is an important factor in preventing internal short circuit in lithium-ion batteries. Local penetration tests (nail or conical punch) often produce presumably sporadic results, where in exactly similar cell and test set-ups one cell goes to thermal runaway while the other shows minimal reactions. We conducted an experimental study of the separators under mechanical loading, and discovered two distinct deformation and failure mechanisms, which could explain the difference in short circuit characteristics of otherwise similar tests. Additionally, by investigation of failure modes, we provided a hypothesis about the process of formation of local "soft short circuits" in cells with undetectable failure. Finally, we proposed a criterion for predicting onset of soft short from experimental data.

Discovery of Chromeno[4,3-c]pyrazol-4(2H)-one Containing Carbonyl or Oxime Derivatives As Potential, Selective Inhibitors PI3Kα

Chemical & Pharmaceutical Bulletin. Sep, 2016  |  Pubmed ID: 27581755

A series of novel chromeno[4,3-c]pyrazol-4(2H)-one containing carbonyl or oxime derivatives (4a-4n, 5a-5n) have been synthesized and evaluated their biological activities as PI3K inhibitors. Out of them, compound 5l showed the most potent antiproliferative activities against HCT-116 with IC50 of 0.10 μM in vitro, and exhibited the most potent activity for PI3Kα with the value of 0.012 μM. Docking simulation of 5l into PI3Kα active site were performed to determine the probable binding model, and it indicated that compound 5l could be optimized as a potential inhibitor of PI3Kα in the further study.

Recent Progress Toward the Use of Circulating MicroRNAs As Clinical Biomarkers

Archives of Toxicology. Sep, 2016  |  Pubmed ID: 27585665

MicroRNAs (miRNAs) have been shown to be critical mediators of many cellular and developmental processes and have been implicated in different human diseases. Since the observation of extracellular miRNAs present in various biofluids, much attention and excitement have been garnered toward understanding the functional roles of these circulating extracellular miRNAs and establishing their potential use as noninvasive diagnostic biomarkers. Here, we will review the current state of miRNA biomarkers for many human diseases, including their emerging use in toxicological applications, and discuss the current challenges in the field, with an emphasis on technical issues that often hinder discovery-based miRNA biomarker studies.

High-risk Factors of Parotid Lymph Node Metastasis in Nasopharyngeal Carcinoma: a Case-control Study

Radiation Oncology (London, England). 2016  |  Pubmed ID: 27586641

Although parotid-sparing IMRT decreased the dose distribution of parotid, parotid region recurrence has been reported. Prophylactic irradiation in parotid area would be necessary in patients with high risk of parotid lymph node metastasis (PLNM). This study was to detect the high-risk factors of PLNM in nasopharyngeal carcinoma.

Nanotopography Promoted Neuronal Differentiation of Human Induced Pluripotent Stem Cells

Colloids and Surfaces. B, Biointerfaces. Aug, 2016  |  Pubmed ID: 27591570

Inefficient neural differentiation of human induced pluripotent stem cells (hiPSCs) motivates recent investigation of the influence of biophysical characteristics of cellular microenvironment, in particular nanotopography, on hiPSC fate decision. However, the roles of geometry and dimensions of nanotopography in neural lineage commitment of hiPSCs have not been well understood. The objective of this study is to delineate the effects of geometry, feature size and height of nanotopography on neuronal differentiation of hiPSCs. HiPSCs were seeded on equally spaced nanogratings (500 and 1000nm in linewidth) and hexagonally arranged nanopillars (500nm in diameter), each having a height of 150 or 560nm, and induced for neuronal differentiation in concert with dual Smad inhibitors. The gratings of 560nm height reduced cell proliferation, enhanced cytoplasmic localization of Yes-associated protein, and promoted neuronal differentiation (up to 60% βIII-tubulin(+) cells) compared with the flat control. Nanograting-induced cell polarity and cytoplasmic YAP localization were shown to be critical to the induced neural differentiation of hiPSCs. The derived neuronal cells express MAP2, Tau, glutamate, GABA and Islet-1, indicating the existence of multiple neuronal subtypes. This study contributes to the delineation of cell-nanotopography interactions and provides the insights into the design of nanotopography configuration for pluripotent stem cell neural lineage commitment.

Molecular Engineering of Mechanochromic Materials by Programmed C-H Arylation: Making a Counterpoint in Chromism Trend

Journal of the American Chemical Society. Sep, 2016  |  Pubmed ID: 27603792

The development of facile accesses for screening organic functional molecules through the C-H bond activation is a revolutionary trend in material research. The prediction of mechanochromism as well as mechanochromic trend of luminogens is an appealing, yet challenging puzzle. Here, we present the design strategy of mechanochromic luminogens on the basis of the dipole moment of donor-acceptor (D-A) molecules. For this purpose, a highly efficient route to 2,7-diaryl [1,2,4]triazolo[1,5-a]pyrimidines (2,7-diaryl TAPs) has been established through the programmed C-H arylation, which unlocks a great opportunity to rapidly assemble a library of fluorophores for the discovery of the mechanochromic regularity. The molecular dipole moment can be employed to explain and further predict the mechanochromic trend. The 2,7-diaryl TAPs with electron-donating groups (EDGs) on 2-aryl and electron-withdrawing groups (EWGs) on 7-aryl possess a relatively small dipole moment and exhibit a red-shifted mechanochromism. While the two aryls are interchanged, the resulting luminogens have a relatively large dipole moment and display a blue-shifted mechanochromism. Seven pairs of isomers with an opposite mechanochromic trend have been given as illustrative examples. The aryl-interchanged congeners with a bidirectional emission shift are structurally similar, which would provide an avenue for deeply understanding the mechanochromic mechanism.

Potential Role of Hyperglycemia in Fetoplacental Endothelial Dysfunction in Gestational Diabetes Mellitus

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2016  |  Pubmed ID: 27606810

Gestational diabetes mellitus (GDM) is associated with structural and functional alterations in various tissues including endothelial dysfunction. The aim of this study was to explore the effects of hyperglycemia on fibroblast growth factor 2 (FGF2)- and vascular endothelial growth factor (VEGF)-stimulated placental angiogenesis and the underlying molecular signaling mechanisms.

Protective Effects of Genistein and Puerarin Against Chronic Alcohol-Induced Liver Injury in Mice Via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms

Journal of Agricultural and Food Chemistry. Sep, 2016  |  Pubmed ID: 27609057

This study aimed to investigate the protective effect of genistein or puerarin on chronic alcohol-induced liver injury in vivo and explore the underlying mechanisms of hepatoprotective effects. Mice were administered with genistein or puerarin (0.3 mmol kg-1 body weight) and gastrically infused with 50% alcohol once per day for 5 weeks. Levels of serum transaminases, serum and hepatic lipid, hepatic antioxidant capacities, inflammation, apoptosis, and histopathological sections were analyzed. Results showed that genistein and puerarin exhibited similar effects in ameliorating alcohol-induced liver injury. However, genistein is more effective than puerarin in decreasing levels of malondialdehyde (1.05 ± 0.0947 vs. 1.28 ± 0.213 nmol/mg pro, p < 0.05), tumor necrosis factor α (3.12 ± 0.498 vs. 3.82 ± 0.277 pg/mg pro, p < 0.05), interleukin-6 (1.46 ± 0.223 vs. 1.88 ± 0.309 pg/mg pro, p < 0.05), whereas puerarin is more effective than genistein in ameliorating serum activities or levels of alanine transaminase (35.8 ± 3.95 vs. 42.6 ± 6.56 U/L, p < 0.05) and low-density lipoprotein cholesterol (1.12 ± 0.160 vs. 1.55 ± 0.150 mmol/L, p < 0.05). In conclusion, both genistein and puerarin effectively alleviates hepatic damage induced by chronic alcohol administration through potential antioxidant, anti-inflammatory, or anti-apoptotic mechanisms.

Resveratrol Supplement Inhibited the NF-κB Inflammation Pathway Through Activating AMPKα-SIRT1 Pathway in Mice with Fatty Liver

Molecular and Cellular Biochemistry. Sep, 2016  |  Pubmed ID: 27613163

Nonalcoholic fatty liver disease (NAFLD) is characterized by high levels of nonesterified fatty acids (NEFA), inflammation, and hepatic steatosis. Inflammation plays a crucial role in the development of fatty liver. Resveratrol (RSV) supplement could improve inflammatory response and hepatic steatosis, whereas the underlying mechanism was not well understood. In this study, mice fed with high-fat diet (HFD) exhibited severe hepatic injury and high blood concentrations of the inflammatory cytokines TNF-α, IL-6, and IL-1β. Hepatic NF-κB inflammatory pathway was over-induced in HFD mice. In vitro, NEFA treatment further increased NF-κB pathway activation in mice hepatocytes, which then promoted the synthesis of inflammatory cytokines. Interestingly, RSV treatment significantly inhibited overactivation of NF-κB pathway and improved hepatic steatosis. Furthermore, RSV further increased the AMP-activated protein kinaseα (AMPKα) phosphorylation and sirtuin1 (SIRT1) protein levels to inhibit overactivation of NF-κB pathway induced by HFD or high levels of NEFA. AMPKα or SIRT1 inhibition significantly decreased the improvement effect of RSV on the NF-κB pathway induced by high levels of NEFA. Taken together, these findings indicate that RSV supplement decreases the inflammatory level and improves hepatic steatosis through activating AMPKα-SIRT1 pathway. Therefore, these data suggested an important clinical application of RSV in preventing NAFLD in humans.

Biliary Cancer: Utility of Next-generation Sequencing for Clinical Management

Cancer. Sep, 2016  |  Pubmed ID: 27622582

Biliary tract cancers (BTCs) typically present at an advanced stage, and systemic chemotherapy is often of limited benefit.

The Effect of Orbital Hybridization on Spin-polarized Tunneling Across Co/C60 Interfaces

ACS Applied Materials & Interfaces. Sep, 2016  |  Pubmed ID: 27624282

The interaction between ferromagnetic surfaces and organic semiconductors leads to the formation of hybrid interfacial states. As a consequence, the local magnetic moment is altered, a hybrid interfacial density of states (DOS) is formed, and spin-dependent shifts of energy levels occur. Here, we show that this hybridization affects spin transport across the interface significantly. We report spin-dependent electronic transport measurements for tunnel junctions comprising C60 molecular thin films grown on top of face-centered-cubic (fcc) epitaxial Co electrodes, an AlOx tunnel barrier, and an Al counter electrode. Since only one ferromagnetic electrode (Co) is present, spin-polarized transport is due to tunneling anisotropic magnetoresistance (TAMR). An in-plane TAMR ratio of approximately 0.7% has been measured at 5 K under application of a magnetic field of 800 mT. The magnetic switching behavior shows some remarkable features, which are attributed to the rotation of interfacial magnetic moments. This behavior can be ascribed to the magnetic coupling between the Co thin films and the newly formed Co/C60 hybridized interfacial states. Using the Tedrow-Meservey technique, the tunnel spin polarization of the Co/C60 interface was found to be 43%.

DCE-MRI-Derived Parameters in Evaluating Abraxane-Induced Early Vascular Response and the Effectiveness of Its Synergistic Interaction with Cisplatin

PloS One. 2016  |  Pubmed ID: 27632532

Our previous studies revealed molecular alterations of tumor vessels, varying from immature to mature alterations, resulting from Abraxane, and demonstrated that the integrin-specific PET tracer 18F-FPPRGD2 can be used to noninvasively monitor such changes. However, changes in the tumor vasculature at functional levels such as perfusion and permeability are also important for monitoring Abraxane treatment outcomes in patients with cancer. The purpose of this study is to further investigate the vascular response during Abraxane therapy and the effectiveness of its synergistic interaction with cisplatin using Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI). Thirty MDA-MB-435 tumor mice were randomized into three groups: PBS control (C group), Abraxane only (A group), and sequential treatment with Abraxane followed by cisplatin (A-P group). Tumor volume was monitored based on caliper measurements. A DCE-MRI protocol was performed at baseline and day 3. The Ktrans, Kep and Ve were calculated and compared with CD31, α-SMA, and Ki67 histology data. Sequential treatment with Abraxane followed by cisplatin produced a significantly greater inhibition of tumor growth during the three weeks of the observation period. Decreases in Ktrans and Kep for the A and A-P groups were observed on day 3. Immunohistological staining suggested vascular remodeling during the Abraxane therapy. The changes in Ktrans and Kep values were correlated with alterations in the permeability of the tumor vasculature induced by the Abraxane treatment. In conclusion, Abraxane-mediated permeability variations in tumor vasculature can be quantitatively visualized by DCE-MRI, making this a useful method for studying the effects of early cancer treatment, especially the early vascular response. Vascular remodeling by Abraxane improves the efficiency of cisplatin delivery and thus results in a favorable treatment outcome.

Altered Expression of A20 Gene in Peripheral Blood Mononuclear Cells is Associated with the Progression of Chronic Hepatitis B Virus Infection

Oncotarget. Sep, 2016  |  Pubmed ID: 27634895

A20 is an important negative immune regulator but its role in chronic hepatitis B virus (HBV) infection is still unknown. This present study was to investigate the potential role of A20 gene in the progression of chronic HBV infection. A total of 236 chronic HBV patients were included and consisted of 63 hepatocellular carcinoma (HCC), 87 liver cirrhosis (LC) and 86 chronic hepatitis B (CHB). The mRNA level of A20 gene in peripheral blood mononuclear cells was determined using quantitative real-time polymerase chain reaction. Receptor operating characteristic curve (ROC) was performed to determine the diagnostic value of A20 mRNA in different stages of chronic HBV infection. A20 mRNA levels in all HBV patients were significantly higher than healthy controls (n=30), of whom HCC and LC patients showed higher A20 mRNA level than CHB patients. In CHB patients, A20 mRNA was closely associated with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. In LC patients, A20 mRNA was significantly associated with ALT, AST, albumin, haemoglobin and platelet. In HCC patients, elevated A20mRNA was also observed in patients with vascular invasion, liver cirrhosis and ascites, compared with those without. ROC analysis revealed that A20 mRNA could effectively discriminate LC from CHB, decompensated LC from compensated LC, and HCC from CHB. In conclusion, A20 mRNA expression in peripheral blood mononuclear cells was associated with dynamic progression of chronic HBV infection. A20 gene might be a potential biomarker to determine the different stages of chronic HBV infection.

High-Yield Preparation and Electrochemical Properties of Few-Layer MoS2 Nanosheets by Exfoliating Natural Molybdenite Powders Directly Via a Coupled Ultrasonication-Milling Process

Nanoscale Research Letters. Dec, 2016  |  Pubmed ID: 27644235

Cost-effective and scalable preparation of two-dimensional (2D) molybdenum disulfide (MoS2) has been the bottleneck that limits their applications. This paper reports a novel coupled ultrasonication-milling (CUM) process to exfoliate natural molybdenite powders to achieve few-layer MoS2 (FL-MoS2) nanosheets in the solvent of N-methyl-2-pyrrolidone (NMP) with polyvinylpyrrolidone (PVP) molecules. The synergistic effect of ultrasonication and sand milling highly enhanced the exfoliation efficiency, and the precursor of natural molybdenite powders minimizes the synthetic cost of FL-MoS2 nanosheets. The exfoliation of natural molybdenite powders was conducted in a home-made CUM system, mainly consisting of an ultrasonic cell disruptor and a ceramic sand mill. The samples were characterized by X-ray diffraction, UV-vis spectra, Raman spectra, FT-IR, SEM, TEM, AFM, and N2 adsorption-desorption. The factors that influence the exfoliation in the CUM process, including the initial concentration of natural molybdenite powders (C in, 15-55 g L(-1)), ultrasonic power (P u, 200-350 W), rotation speed of sand mill (ω s, 1500-2250 r.p.m), exfoliation time (t ex, 0.5-6 h), and the molar ratio of PVP unit to MoS2 (R pm, 0-1), were systematically investigated. Under the optimal CUM conditions (i.e., C in = 45 g L(-1), P u = 280 W, ω s = 2250 r.p.m and R pm = 0.5), the yield at t ex = 6 h reaches 21.6 %, and the corresponding exfoliation rate is as high as 1.42 g L(-1) h(-1). The exfoliation efficiency of the CUM mode is much higher than that of either the ultrasonication (U) mode or the milling (M) mode. The synergistic mechanism and influencing rules of the CUM process in exfoliating natural molybdenite powders were elaborated. The as-obtained FL-MoS2 nanosheets have a high specific surface area of 924 m(2) g(-1) and show highly enhanced electrocatalytic performance in hydrogen evolution reaction and good electrochemical sensing property in detecting ascorbic acid. The CUM process developed has paved a low-cost, green, and highly efficient way towards FL-MoS2 nanosheets from natural molybdenite powders.

Characterization and Prediction of Protein Flexibility Based on Structural Alphabets

BioMed Research International. 2016  |  Pubmed ID: 27660756

Motivation. To assist efforts in determining and exploring the functional properties of proteins, it is desirable to characterize and predict protein flexibilities. Results. In this study, the conformational entropy is used as an indicator of the protein flexibility. We first explore whether the conformational change can capture the protein flexibility. The well-defined decoy structures are converted into one-dimensional series of letters from a structural alphabet. Four different structure alphabets, including the secondary structure in 3-class and 8-class, the PB structure alphabet (16-letter), and the DW structure alphabet (28-letter), are investigated. The conformational entropy is then calculated from the structure alphabet letters. Some of the proteins show high correlation between the conformation entropy and the protein flexibility. We then predict the protein flexibility from basic amino acid sequence. The local structures are predicted by the dual-layer model and the conformational entropy of the predicted class distribution is then calculated. The results show that the conformational entropy is a good indicator of the protein flexibility, but false positives remain a problem. The DW structure alphabet performs the best, which means that more subtle local structures can be captured by large number of structure alphabet letters. Overall this study provides a simple and efficient method for the characterization and prediction of the protein flexibility.

Improving the Modulation Bandwidth of LED by CdSe/ZnS Quantum Dots for Visible Light Communication

Optics Express. Sep, 2016  |  Pubmed ID: 27661896

Visible light communication (VLC) is an advanced and high-efficiency wireless communication technology. As one of the most important light sources in VLC, conventional white light emitting diode (WLED) based on Y3Al5O12:Ce3+ (YAG:Ce) phosphor limits the system transmitting rate severely due to its narrow modulation bandwidth. Considering the short fluorescent lifetime of quantum dots (QDs), QD-LEDs with wide modulation bandwidths were designed here to improve the transmitting rate of VLC. CdSe/ZnS core/shell QDs and related luminescent microspheres (LMS) were implemented as light conversion materials for the QD-LEDs. Compared with conventional phosphor WLED, the proposed QD-LED and QD-WLED reached maximum improvement on modulation bandwidth at 74.19% and 67.75% respectively. Furthermore, mathematical modeling of smearing was analyzed to establish the relationship between fluorescent lifetime and modulation bandwidth. Our findings will provide an effective solution of white LEDs for high speed VLC.

Laparoscopic Transcystic Common Bile Duct Exploration: Advantages over Laparoscopic Choledochotomy

PloS One. 2016  |  Pubmed ID: 27668730

The ideal treatment for choledocholithiasis should be simple, readily available, reliable, minimally invasive and cost-effective for patients. We performed this study to compare the benefits and drawbacks of different laparoscopic approaches (transcystic and choledochotomy) for removal of common bile duct stones.

Arid5a Exacerbates IFN-γ-mediated Septic Shock by Stabilizing T-bet MRNA

Proceedings of the National Academy of Sciences of the United States of America. Oct, 2016  |  Pubmed ID: 27671645

Adenine-thymine (AT)-rich interactive domain containing protein 5a (Arid5a) is an RNA-binding protein that has been shown to play an important immune regulatory function via the stabilization of IL-6 and STAT3 mRNA. However, the role of Arid5a in the overwhelming and uncontrolled immune response that leads to septic shock is unknown. Here, we report that Arid5a-deficient mice are highly resistant to lipopolysaccharide (LPS)-induced endotoxic shock and secrete lower levels of major proinflammatory cytokines, including IFN-γ, IL-6, and TNF-α, than WT mice in response to LPS. Arid5a deficiency resulted in decreased levels of IFN-γ under Th1 cell conditions, in which T-box expressed in T cells (T-bet) mRNA expression was inhibited. Arid5a bound to the conserved stem loop structure of the 3'UTR of T-bet and stabilized its mRNA. Arid5a-deficient mice were also resistant to Propionibacterium acnes-primed LPS injection, which is considered to be a T-cell-mediated IFN-γ dependent endotoxic shock mouse model. Thus, regulation of IFN-γ by Arid5a via the stabilization of T-bet mRNA in Th1 cells contributes to the development of septic shock in mice. In addition, our previous study suggests that Arid5a control the IL-6 level in vivo in response to LPS by stabilization of IL-6 mRNA. We also observed that neutralization of IFN-γ and IL-6 significantly recovered the mice from endotoxic shock. Taken together, we conclude that Arid5a regulates the augmentation of IL-6 and IFN-γ in response to LPS, which possibly works synergistically for amplification of various other cytokines that ultimately cause the development of septic shock in mice.

Folic Acid Supports Pluripotency and Reprogramming by Regulating LIF/STAT3 and MAPK/ERK Signaling

Stem Cells and Development. Nov, 2016  |  Pubmed ID: 27676194

Pluripotent stem cells act as an excellent cell source for disease therapy because of its specific characteristics of self-renewal and differentiation. Pluripotent stem cells are heterogeneous, consisting of naive stem cells as well as primed epiblast stem cells. However, the strategies and mechanisms of maintaining naive pluripotent stem cells remain unclear. In this study, we found that folic acid (FA) sustained mouse embryonic stem cell (ESC) pluripotency and enabled long-term maintenance of the naive state of ESCs under CHIR99021 conditions. Mechanistic experiments showed that STAT3 pathway partially mediated the effect of FA after which the interaction between STAT3 and importin α5 was enhanced. Meanwhile, MEK/ERK signaling also acted downstream of FA in maintaining ESC pluripotency. Furthermore, FA significantly promoted mouse somatic cell reprogramming. Overall, our study identified an effective chemical condition for maintaining homogeneous ESCs and highlighted the important roles of LIF/STAT3 and MEK/ERK signaling in naive ESC pluripotency.

Homer1a Attenuates Glutamate-induced Oxidative Injury in HT-22 Cells Through Regulation of Store-operated Calcium Entry

Scientific Reports. Sep, 2016  |  Pubmed ID: 27681296

Calcium disequilibrium is extensively involved in oxidative stress-induced neuronal injury. Although Homer1a is known to regulate several neuronal calcium pathways, its effects on, or its exact relationship with, oxidative stress-induced neuronal injury has not yet been fully elucidated. We found that Homer1a protected HT-22 cells from glutamate-induced oxidative stress injury by inhibiting final-phase intracellular calcium overload and mitochondrial oxidative stress. In these cells, stromal interactive molecule 1 (STIM1) puncta, but not the protein level, was significantly increased after glutamate treatment. Store-operated calcium entry (SOCE) inhibitors and cells in which a key component of SOCE (STIM1) was knocked out were used as glutamate-induced oxidative stress injury models. Both models demonstrated significant improvement of HT-22 cell survival after glutamate treatment. Additionally, increased Homer1a protein levels significantly inhibited SOCE and decreased the association of STIM1-Orai1 triggered by glutamate. These results suggest that up-regulation of Homer1a can protect HT-22 cells from glutamate-induced oxidative injury by disrupting the STIM1-Oria1 association, and then by inhibiting the SOCE-mediated final-phrase calcium overload. Thus, regulation of Homer1a, either alone or in conjunction with SOCE inhibition, may serve as key therapeutic interventional targets for neurological diseases in which oxidative stress is involved in the etiology or progression of the disease.

Bioactive Sesquiterpenes from the Edible Mushroom Flammulina Velutipes and Their Biosynthetic Pathway Confirmed by Genome Analysis and Chemical Evidence

The Journal of Organic Chemistry. Oct, 2016  |  Pubmed ID: 27684789

Twelve putative sesquiterpene synthases genes were found in clades along with enzymes with 1,6-, 1,10-, and 1,11-cyclase activities in the genome of Flammulina velutipes. Chemistry investigation of F. velutipes led to the identification of two seco-cuparane sesquiterpenes, flammufuranone A (1) and B (2); 13 new sesquiterpenes with nor-eudesmane, spiroaxane, cadinane, and cuparane skeletons (3-14, 16); as well as two new ergosterol derivatives (17 and 18). Sesquiterpenes (3-14) derived from 1,10-cyclizing enzyme were first reported from this mushroom. The absolute configurations in 1 (3R,7S) and 2 (3R,7R) were assigned by electronic circular dichroism (ECD) calculation. The absolute configuration in 3 was confirmed by X-ray diffraction analysis. The absolute configurations in the 1,2-diol moiety of 13, and in the 1,3-diol moiety of 17 and 18 were determined using Snatzke's method. Among these compounds, 3, 5, 13, and 14 were found to inhibit the HMG-CoA reductase with IC50 of 114.7, 77.6, 55.5, and 87.1 μM, respectively. Compounds 5, 6, 7, 10, 13, and 14 showed DPP-4 inhibitory activity with IC50 of 75.9, 83.7, 70.9, 79.7, 80.5, and 74.8 μM, respectively. The biosynthesis for sesquiterpenes in F. velutipes was also discussed.

SparkText: Biomedical Text Mining on Big Data Framework

PloS One. 2016  |  Pubmed ID: 27685652

Many new biomedical research articles are published every day, accumulating rich information, such as genetic variants, genes, diseases, and treatments. Rapid yet accurate text mining on large-scale scientific literature can discover novel knowledge to better understand human diseases and to improve the quality of disease diagnosis, prevention, and treatment.

Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study

Ophthalmology. Dec, 2016  |  Pubmed ID: 27707548

Primary open-angle glaucoma (POAG) is a major cause of blindness and visual disability. Several genetic risk factors for POAG and optic nerve features have been identified. We measured the relative risk for glaucoma that these factors contribute to participants in the Ocular Hypertension Treatment Study (OHTS).

LncScore: Alignment-free Identification of Long Noncoding RNA from Assembled Novel Transcripts

Scientific Reports. Oct, 2016  |  Pubmed ID: 27708423

RNA-Seq based transcriptome assembly has been widely used to identify novel lncRNAs. However, the best-performing transcript reconstruction methods merely identified 21% of full-length protein-coding transcripts from H. sapiens. Those partial-length protein-coding transcripts are more likely to be classified as lncRNAs due to their incomplete CDS, leading to higher false positive rate for lncRNA identification. Furthermore, potential sequencing or assembly error that gain or abolish stop codons also complicates ORF-based prediction of lncRNAs. Therefore, it remains a challenge to identify lncRNAs from the assembled transcripts, particularly the partial-length ones. Here, we present a novel alignment-free tool, lncScore, which uses a logistic regression model with 11 carefully selected features. Compared to other state-of-the-art alignment-free tools (e.g. CPAT, CNCI, and PLEK), lncScore outperforms them on accurately distinguishing lncRNAs from mRNAs, especially partial-length mRNAs in the human and mouse datasets. In addition, lncScore also performed well on transcripts from five other species (Zebrafish, Fly, C. elegans, Rat, and Sheep). To speed up the prediction, multithreading is implemented within lncScore, and it only took 2 minute to classify 64,756 transcripts and 54 seconds to train a new model with 21,000 transcripts with 12 threads, which is much faster than other tools. lncScore is available at https://github.com/WGLab/lncScore.

Roxarsone Induces Angiogenesis Via PI3K/Akt Signaling

Cell & Bioscience. 2016  |  Pubmed ID: 27708768

3-Nitro-4-hydroxy phenyl arsenic acid, roxarsone, is widely used as an organic arsenic feed additive for livestock and poultry, which may increase the level of arsenic in the environment and the risk of exposure to arsenic in human. Little information is focused on the angiogenesis roxarsone-induced and its mechanism at present. This paper aims to study the role of PI3K/Akt signaling in roxarsone-induced angiogenesis in rat vascular endothelial cells and a mouse B16-F10 melanoma xenograft model.

Theoretical Investigation of the Singlet-triplet Splittings for Carbazole-based Thermally Activated Delayed Fluorescence Emitters

Physical Chemistry Chemical Physics : PCCP. Sep, 2016  |  Pubmed ID: 27722283

Accurate prediction of singlet-triplet splittings (ΔESTs) is a key issue for the design of thermally activated delayed fluorescence (TADF) emitters. Due to the evident changes between ground- and excited-state electronic structures, the ΔESTs of carbazole (Cz)-based TADF emitters can't be accurately predicted based on the current optimal Hartree-Fock percentage (HF%) (OHF) method. To address this issue, here, we used the adiabatic excitation energy method to accurately predict the ΔESTs of the TADF emitters with different geometries of ground- and excited-states by calculating the minimum potential energy differences between the ground- and excited-states considering the relaxation effect. With the optimized excited states using the B3LYP functional, the theoretically calculated values of ΔESTs based on our method are well consistent with the experimental results for the Cz-based TADF emitters, obviously improved compared with the calculated results based on the OHF method. These results indicate that the adiabatic excitation energy method with the B3LYP functional is a general and accurate way to predict the ΔESTs of Cz-based TADF emitters.

Strand-specific RNA-Seq Transcriptome Analysis of Genotypes with and Without Low-phosphorus Tolerance Provides Novel Insights into Phosphorus-use Efficiency in Maize

BMC Plant Biology. Oct, 2016  |  Pubmed ID: 27724863

Phosphorus (P) stress is a global problem in maize production. Although macro/microarray technologies have greatly increased our general knowledge of maize responses to P stress, a greater understanding of the diversity of responses in maize genotypes is still needed.

SOX17 is a Tumor Suppressor in Endometrial Cancer

Oncotarget. Oct, 2016  |  Pubmed ID: 27738313

β-catenin is a key regulatory factor for the Wnt signaling pathway. SOX17 is an important β-catenin inhibitor, while MAML3 is a co-activator of β-catenin-mediated transcription. Out of 120 endometrial cancer (EC) patients, we found that those with tumors expressing higher SOX17 (n=68) had longer recurrence-free survival (P=0.024), while higher MAML3 expression (n=76) was associated with shorter recurrence-free survival (P=0.022). Immunohistochemical and immunoprecipitation analyses revealed that SOX17 and MAML3 co-localized in EC cell nuclei, and the MAML3 C-terminal region was necessary for SOX17 binding. SOX17 regulated MAML3 transcription via binding to the MAML3 promoter, decreasing Wnt pathway protein expression and suppressing EC cell growth and colony formation in vitro. In nude mice, SOX17 over-expression inhibited tumor growth, and co-inhibition or co-overexpression of SOX17 and MAML3 rescued this response. Our results suggest that decreasing SOX17 levels may promote EC development and progression, and that by downregulating MAML3 expression and Wnt signaling, SOX17 acts as a tumor suppressor that may improve outcome in patients with EC.

Efficiency and Safety of Roflumilast Combined with Long-acting Bronchodilators on Moderate-to-severe Stable Chronic Obstructive Pulmonary Disease Patients: a Meta-analysis

Journal of Thoracic Disease. Sep, 2016  |  Pubmed ID: 27747018

Roflumilast, a phosphodiesterase-4 inhibitor recommended by clinical guideline, is always being used in combination with at least one long-acting bronchodilator in patients with stable chronic obstructive pulmonary disease (COPD). However, there are few evidences about whether the combination of roflumilast and long-acting bronchodilators is safer and more effective in patients with moderate-to-very severe stable COPD. In our study, we investigate the effect and safety of roflumilast combined with long-acting bronchodilators on moderate-to-severe stable COPD patients.

ISH ADA-02 COMPARISON OF PULSE WAVE VELOCITY AND PULSE PRESSURE AMPLIFICATION IN THE ASSOCIATION WITH TARGET ORGAN DAMAGES IN THE COMMUNITY-BASED ELDERLY: THE NORTHERN SHANGHAI STUDY

Journal of Hypertension. Sep, 2016  |  Pubmed ID: 27753881

To investigate the discrepancy between PWV and PPA in association with hypertensive TODs in the elderly population.

OS 18-08 OPTIMAL BLOOD PRESSURE GOAL FOR THE ELDERLY CHINESE: THE FINDINGS FROM THE NORTHERN SHANGHAI STUDY

Journal of Hypertension. Sep, 2016  |  Pubmed ID: 27754076

The Eighth Joint National Committee Panel recommended novel blood pressure (BP) goals for individuals with hypertension, which is still under debate. We therefore assessed patients' target organ damages in controlled hypertensives defined by the Seventh or Eighth Joint National Committee thresholds (JNC7 and JNC8) in a community-based elderly Chinese population, in order to find the optimal BP goal for the elderly Chinese.

OS 20-02 HYPERTENSIVE TARGET ORGAN DAMAGES ARE BETTER ASSOCIATED WITH CENTRAL THAN BRACHIAL BLOOD PRESSURE: THE NORTHERN SHANGHAI STUDY

Journal of Hypertension. Sep, 2016  |  Pubmed ID: 27754088

Central blood pressure (BP) is reported to associate with target organ damages (TODs) better than brachial BP. However, data regarding the association of TODs with central and brachial BP in the community-dwelling health elderly are scare. We therefore hypothesized that TODs are better associated with central than brachial blood pressure (BP) in the elderly community-based population, with considering all hypertensive TODs, namely left ventricular hypertrophy (LVH), left ventricular (LV) diastolic dysfunction (DD), carotid plaque, arteriosclerosis and microalbuminuria.

Ultrafast Charge Transfer and Hybrid Exciton Formation in 2D/0D Heterostructures

Journal of the American Chemical Society. Oct, 2016  |  Pubmed ID: 27754655

Photoinduced interfacial charge transfer is at the heart of many applications, including photovoltaics, photocatalysis, and photodetection. With the emergence of a new class of semiconductors such as monolayer two-dimensional transition metal dichalcogenides (2D-TMDs), charge transfer at the 2D/2D heterojunctions attracted several efforts due to the remarkable optical and electrical properties of 2D-TMDs. Unfortunately, in 2D/2D heterojunctions, for a given combination of two materials, the relative energy band alignment and the charge transfer efficiency are locked. Due to their large variety and broad size tunability, semiconductor quantum dots (0D-QDs) interfaced with 2D-TMDs may become an attractive heterostructure for optoelectronic applications. Here, we incorporate femtosecond pump-probe spectroscopy to reveal the sub-45 fs charge transfer at a 2D/0D heterostructure composed of tungsten disulfide monolayers (2D-WS2) and a single layer of cadmium selenide (CdSe)/zinc sulfide (ZnS) core/shell 0D-QDs. Furthermore, ultrafast dynamics and steady-state measurements suggested that following electron transfer from the 2D to the 0D, hybrid excitons (HXs), wherein the electron resides in the 0D and hole resides in the 2D-TMD monolayer, are formed with a binding energy on the order of ~140 meV, which is several times lower than that of tightly bound excitons in 2D-TMDs.

Targeted Co-delivery of PTX and TR3 SiRNA by PTP Peptide Modified Dendrimer for the Treatment of Pancreatic Cancer

Small (Weinheim an Der Bergstrasse, Germany). Oct, 2016  |  Pubmed ID: 27762495

A new type of tumor-targeted nanovehicle peptide-conjugated PSPG (PSPGP) is successfully synthesized for co-delivery of paclitaxel (PTX) and TR3 small interfering RNA (siRNA). In vitro and in vivo investigations demonstrate that the redox-responsive PSPGP exhibit enhanced endosomal escape and intracellular degradation, which facilitate PTX and TR3 siRNA release, effectively improving the antitumor efficacy.

Temporal Dynamics of Bacterioplankton Communities in Response to Excessive Nitrate Loading in Oligotrophic Coastal Water

Marine Pollution Bulletin. Oct, 2016  |  Pubmed ID: 27773533

Coastal ecosystems are receiving elevated loads of nitrogen (N) from anthropogenic sources. Understanding how excessive N loading affects bacterioplankton communities is critical to predict the biodiversity of marine ecosystems under conditions of eutrophic disturbance. In this study, oligotrophic coastal water microcosms were perturbed with nitrate in two loading modes: 1) one-off loading at the beginning of the incubation period; and 2) periodic loading every two days for 16days. Turnover in the bacterioplankton community was investigated by 16S rDNA gene amplicon sequencing. The alpha diversity of the bacterioplankton community showed great temporal variability and similar responses to the different treatments. Bacterioplankton community composition was influenced remarkably by time and N loading mode. The effects of N loading on bacterioplankton community structure showed obvious temporal variation, probably because of the great temporal variation in environmental parameters. This study provides insights into the effects of N pollution in anthropogenically perturbed marine environments.

Nlrp12 Mutation Causes C57BL/6J Strain-specific Defect in Neutrophil Recruitment

Nature Communications. Oct, 2016  |  Pubmed ID: 27779193

The inbred mouse strain C57BL/6J is widely used in models of immunological and infectious diseases. Here we show that C57BL/6J mice have a defect in neutrophil recruitment to a range of inflammatory stimuli compared with the related C57BL/6N substrain. This immune perturbation is associated with a missense mutation in Nlrp12 in C57BL/6J mice. Both C57BL/6J and NLRP12-deficient mice have increased susceptibility to bacterial infection that correlates with defective neutrophil migration. C57BL/6J and NLRP12-deficient macrophages have impaired CXCL1 production and the neutrophil defect observed in C57BL/6J and NLRP12-deficient mice is rescued by restoration of macrophage NLRP12. These results demonstrate that C57BL/6J mice have a functional defect in NLRP12 and that macrophages require NLRP12 expression for effective recruitment of neutrophils to inflammatory sites.

Angiotensin II Promotes the Development of Carotid Atherosclerosis in Type 2 Diabetes Patients Via Regulating the T Cells Activities: A Cohort Study

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. Oct, 2016  |  Pubmed ID: 27782101

BACKGROUND Specific T cell phenotype has been reported to potentially contribute to the development of angiotensin II (Ang II)-induced several vascular disorders. Type 2 diabetes mellitus (T2DM) is intimately associated with cardiovascular disease. The present study aimed to investigate the relationship between T cell phenotypes and Ang II in T2DM patients combined with carotid atherosclerosis (CA). MATERIAL AND METHODS This study was performed on 50 patients with T2DM in our hospital. Based on the presence of CA, they were divided into CA group (presence of CA, n=30) or T2DM group (absence of CA, n=20). Additionally, 10 healthy participants were selected as controls. Basic characteristics of all participants were collected and recorded. Peripheral blood mononuclear cells (PBMCs) isolated from patients and controls with or without Ang II and Ang II receptor blocker (ARB) treatment were used to detect Th1, Th2, and Th17 cell proportions, mRNA levels of T-bet, GATA3, and RORγt as well as the expression of IFN-γ, IL-4, and IL-17 by flow cytometry, ELISA, and Real-Time PCR. RESULTS Ang II levels were notably higher in patients in the CA group than those in the T2DM and control group (p<0.05). Th1 and Th17 positive cells, mRNA levels of T-bet and RORgt as well as the expression of IFN-γ and IL-17 were significantly increased in the CA group compared with the T2DM group and control group (p<0.05). Moreover, the activities of T cells and related cytokines were significantly increased of healthy controls after Ang II treatment (p<0.05), while these changes were notably weakened by ARB treatment (p<0.05). CONCLUSIONS Ang II promotes the development of CA in T2DM patients by regulating T cells activities.

Hedgehog Pathway Dysregulation Contributes to the Pathogenesis of Human Gastrointestinal Stromal Tumors Via GLI-mediated Activation of KIT Expression

Oncotarget. Oct, 2016  |  Pubmed ID: 27793025

Gastrointestinal stromal tumors (GIST) arise within the interstitial cell of Cajal (ICC) lineage due to activating KIT/PDGFRA mutations. Both ICC and GIST possess primary cilia (PC), which coordinate PDGFRA and Hedgehog signaling, regulators of gastrointestinal mesenchymal development. Therefore, we hypothesized that Hedgehog signaling may be altered in human GIST and controls KIT expression. Quantitative RT-PCR, microarrays, and next generation sequencing were used to describe Hedgehog/PC-related genes in purified human ICC and GIST. Genetic and pharmacologic approaches were employed to investigate the effects of GLI manipulation on KIT expression and GIST cell viability. We report that Hedgehog pathway and PC components are expressed in ICC and GIST and subject to dysregulation during GIST oncogenesis, irrespective of KIT/PDGFRA mutation status. Using genomic profiling, 10.2% of 186 GIST studied had potentially deleterious genomic alterations in 5 Hedgehog-related genes analyzed, including in the PTCH1 tumor suppressor (1.6%). Expression of the predominantly repressive GLI isoform, GLI3, was inversely correlated with KIT mRNA levels in GIST cells and non-KIT/non-PDGFRA mutant GIST. Overexpression of the 83-kDa repressive form of GLI3 or small interfering RNA-mediated knockdown of the activating isoforms GLI1/2 reduced KIT mRNA. Treatment with GLI1/2 inhibitors, including arsenic trioxide, significantly increased GLI3 binding to the KIT promoter, decreased KIT expression, and reduced viability in imatinib-sensitive and imatinib-resistant GIST cells. These data offer new evidence that genes necessary for Hedgehog signaling and PC function in ICC are dysregulated in GIST. Hedgehog signaling activates KIT expression irrespective of mutation status, offering a novel approach to treat imatinib-resistant GIST.

Epithelial Disruption of Gab1 Perturbs Surfactant Homeostasis and Predisposes Mice to Lung Injuries

American Journal of Physiology. Lung Cellular and Molecular Physiology. Oct, 2016  |  Pubmed ID: 27793798

GRB2-associated-binding protein 1 (Gab1) belongs to Gab adaptor family (Gabs), which integrates multiple signals in response to the epithelial growth factors. Recent genetic studies identified genetic variants of human Gab1 gene as potential risk factors of asthmatic inflammation. However, Gab1 functions in lungs remain largely unknown. Alveolar type-II cells (AT-IIs) are responsible for surfactant homeostasis, and essentially regulate lung inflammation following various injuries. Here, in vitro knockdown of Gab1 was shown to cause a decrease in surfactant proteins (SPs) in AT-IIs. We further examined in vivo Gab1 functions by generating alveolar epithelium-specific Gab1 knockout mice (Gab1∆/∆). In vivo Gab1 deficiency leads to a decrease in SP synthesis and the appearance of disorganized lamellar bodies. Histological examination shows no apparent pathological alterations or inflammation in the lung sections obtained from Gab1∆/∆, compared with the controls. However, Gab1∆/∆ mice demonstrate inflammatory responses during the LPS-induced acute lung injury. Similarly, in mice challenged with bleomycin (BLM), fibrotic lesions were shown to be aggravated in Gab1∆/∆. These observations suggest that the abolishment of Gab1 in AT-IIs impairs SP homeostasis, predisposing mice to lung injuries. Additionally, we observed that the production of surfactants in AT-IIs overexpressing Gab1 mutants, in which Shp2 phosphatase and PI3K kinase binding sites have been mutated (Gab1ΔShp2, Gab1ΔPI3K), has been considerably attenuated. Together, these findings provide the first evidence of the roles of docking protein Gab1 in lungs, adding to our understanding of acute and interstitial lung diseases caused by the disruption of alveolar SP homeostasis.

Enhanced Sensitivity and Piezochromic Contrast Through Single-Direction Extension of Molecular Structure

Chemistry (Weinheim an Der Bergstrasse, Germany). Oct, 2016  |  Pubmed ID: 27796058

Two piezochromic materials containing phenanthro[9,10-d]imidazole and tetraphenylethylene are developed. A supra-amplification piezochromic effect originated from their various long-to-short axis ratios is found in the high-pressure experiments. Based on the linear relationship between applied pressure and emission peak wavelength during pressurizing and depressurizing cycles, quantitative sensitivity for piezochromism can be denoted. M2 displays higher piezochromic contrast (102 nm) and better sensitivity (11.19 nm/GPa) than M1 (69 nm and 6.12 nm/GPa), which helps to develop a more comprehensive general strategy to evaluate pressure-responsive performance.

Correction to Protective Effects of Genistein and Puerarin Against Chronic Alcohol-Induced Liver Injury in Mice Via Antioxidant, Anti-inflammatory, and Anti-apoptotic Mechanisms

Journal of Agricultural and Food Chemistry. Oct, 2016  |  Pubmed ID: 27797200

Globus Pallidus Interna in Tourette Syndrome: Decreased Local Activity and Disrupted Functional Connectivity

Frontiers in Neuroanatomy. 2016  |  Pubmed ID: 27799898

Globus pallidus interna (GPi) is an effective deep brain stimulation site for the treatment of Tourette syndrome (TS), and plays a crucial role in the pathophysiology of TS. To investigate the functional network feature of GPi in TS patients, we retrospectively studied 24 boys with 'pure' TS and 32 age-/education-matched healthy boys by resting state functional magnetic resonance images. Amplitude of low-frequency fluctuation (ALFF) and functional connectivity were used to estimate the local activity in GPi and its functional coordinate with the whole brain regions, respectively. We found decreased ALFF in patients' bilateral GPi, which was also negatively correlated with clinical symptoms. Functional connectivity analysis indicated abnormal regions within motor and motor-control networks in patients (inferior part of sensorimotor area, cerebellum, prefrontal cortex, cingulate gyrus, caudate nucleus, and brain stem). Transcranial magnetic stimulation sites defined by previous studies ("hand knob" area, premotor area, and supplementary motor area) did not show significantly different functional connectivity with GPi between groups. In summary, this study characterized the disrupted functional network of GPi and provided potential regions-of-interest for further basic and clinical studies on TS.

Self-templated Growth of Vertically Aligned 2H-1T MoS2 for Efficient Electrocatalytic Hydrogen Evolution

ACS Applied Materials & Interfaces. Nov, 2016  |  Pubmed ID: 27801573

Semiconductor heterostructures of two-dimensional (2D) transition metal disulfide (TMD) have opened up approaches toward the integration of each functions and implementations in novel energy and electronic devices. However, engineering TMD-based homostructures with tailored properties is still challenging. Herein, we demonstrate a solution-processed growth of vertically aligned 1T-MoS2 using liquid-phase exfoliated 2H-MoS2 as self templates. The unique MoS2-based homostructures not only provide more exposed active sites in edge and basal plane for the electrocatalytic hydrogen evolution reaction (HER), but also improve the mass transfer due to the introduction of high packing porosity. The resultant all-MoS2 electrocatalysts with an integration of polymorphous MoS2 nanostructures exhibit a superior HER activity with a low potential of 203 mV at 10 mA cm-2, a small Tafel slope of 60 mV dec-1 and a remarkable cyclic stability. This work thus provides a simple and efficient route for the creation of unprecedented MoS2-based homostructured materials with exciting properties, especially as an inexpensive alternative to platinum catalysts in electrochemical hydrogen evolution production.

Release of Cell-free MicroRNA Tumor Biomarkers into the Blood Circulation with Pulsed Focused Ultrasound: A Noninvasive, Anatomically Localized, Molecular Liquid Biopsy

Radiology. Nov, 2016  |  Pubmed ID: 27802108

Purpose To compare the abilities of three pulsed focused ultrasound regimes (that cause tissue liquefaction, permeabilization, or mild heating) to release tumor-derived microRNA into the circulation in vivo and to evaluate release dynamics. Materials and Methods All rat experiments were approved by the University of Washington Institutional Animal Care and Use Committee. Reverse-transcription quantitative polymerase chain reaction array profiling was used to identify candidate microRNA biomarkers in a rat solid tumor cell line. Rats subcutaneously grafted with these cells were randomly assigned among three pulsed focused ultrasound treatment groups: (a) local tissue liquefaction via boiling histotripsy, (b) tissue permeabilization via inertial cavitation, and (c) mild (<10°C) heating of tissue, as well as a sham-treated control group. Blood specimens were drawn immediately prior to treatment and serially over 24 hours afterward. Plasma microRNA was quantified with reverse-transcription quantitative polymerase chain reaction, and statistical significance was determined with one-way analysis of variance (Kruskal-Wallis and Friedman tests), followed by the Dunn multiple-comparisons test. Results After tissue liquefaction and cavitation treatments (but not mild heating), plasma quantities of candidate biomarkers increased significantly (P value range, <.0001 to .04) relative to sham-treated controls. A threefold to 32-fold increase occurred within 15 minutes after initiation of pulsed focused ultrasound tumor treatment, and these increases persisted for 3 hours. Histologic examination confirmed complete liquefaction of the targeted tumor area with boiling histotripsy, in addition to areas of petechial hemorrhage and tissue disruption by means of cavitation-based treatment. Conclusion Mechanical tumor tissue disruption with pulsed focused ultrasound-induced bubble activity significantly increases the plasma abundance of tumor-derived microRNA rapidly after treatment. (©) RSNA, 2016 Online supplemental material is available for this article.

Impairment of the Executive Attention Network in Premenopausal Women with Hormone Receptor-positive Breast Cancer Treated with Tamoxifen

Psychoneuroendocrinology. Oct, 2016  |  Pubmed ID: 27815995

Tamoxifen (TAM) is most commonly prescribed for patients with hormone-sensitive breast cancer and exerts agonistic/antagonistic effects on estrogen receptors throughout the body. Accumulating evidence has revealed that breast cancer patients receiving TAM manifest cognitive dysfunction. However, whether these patients have a global attention deficit or a more selective impairment of specific attention networks remains unknown. In the present study, we sought to explore the attention function of premenopausal women with hormone receptor-positive breast cancer treated with TAM using the attention network test (ANT). The subjects included breast cancer patients receiving TAM (TAM, N=43), breast cancer patients not receiving TAM (non-TAM, N=41), and matched healthy controls (HC, N=46). The subjects completed the ANT and neuropsychological tests, which measure three independent attention networks and executive function performance, respectively. Our results indicated that patients in the TAM group had significant deficits in their executive control component but not in the alerting or orienting components. Moreover, the patients showed poor executive function performance in the neuropsychological tests. Additionally, in the TAM group, significant correlations were found between the decreased efficiency of the executive control component and their reduced performance in executive function tests. This study demonstrates that premenopausal women with hormone receptor-positive breast cancer treated with TAM have impairment of the executive attention network and that this impairment was associated with differences in executive function performance.

Lysine- and Cysteine-based Protein Adductions Derived from Toxic Metabolites of 8-epidiosbulbin E Acetate

Toxicology Letters. Nov, 2016  |  Pubmed ID: 27816466

Furanoid 8-epidiosbulbin E acetate (EEA) is a major constituent of herbal medicine Dioscorea bulbifera L. (DB), a traditional herbal medicine widely used in Asian nations. Our early studies demonstrated that administration of EEA caused acute hepatotoxicity in mice and the observed toxicity required P450-mediated metabolic activation. Protein modification by reactive metabolites of EEA has been suggested to be an important mechanism of EEA-induced hepatotoxicity. The objectives of the present study were to investigate the interaction of the electrophilic reactive metabolites derived from EEA with lysine and cysteine residues of proteins and to define the correlation of protein adductions of EEA and the hepatotoxicity induced by EEA. EEA-derived cis-enedial was found to modify both lysine and cysteine residues of proteins. The observed modifications increased with the increase in doses administered in the animals. The formation of protein adductions derived from the reactive metabolites of EEA were potentiated by buthionine sulfoximine, but were attenuated by ketoconazole. This work facilitated better understanding of the mechanisms of toxic action of EEA.

One-step Radiosynthesis of (18)F-IRS: A Novel Radiotracer Targeting Mutant EGFR in NSCLC for PET/CT Imaging

Bioorganic & Medicinal Chemistry Letters. Dec, 2016  |  Pubmed ID: 27825546

EGFR (epidermal growth factor receptor) targeted therapy has shown great success in clinical comparing with chemotherapy in EGFR mutation NSCLCs. Such as, gefitinib, first generation EGFR TKI, has obviously prolonged the FPS (progression free survival) of the subgroup of patients, but to those who did not get a certain mutation in EGFR kinase domain, the outcome is poor. In view of this situation, scientists have synthesized many radiotracers for selecting the right people by PET/CT imaging to NSCLC TKI therapy. In this study, we developed a novel PET radiotracer (18)F-IRS in one-step with a radio yield 20% (non-corrected), radiochemistry>98.5%, specific activity>105GBq/μmol, the pharmacokinetics and capacity of the tracer binding to mutant EGFR were evaluated both in vitro and in vivo.

Effective Coupled Optoelectrical Design Method for Fully Infiltrated Semiconductor Nanowires Based Hybrid Solar Cells

Optics Express. Oct, 2016  |  Pubmed ID: 27828520

We present a novel coupled design method that both optimizes light absorption and predicts electrical performance of fully infiltrated inorganic semiconductor nanowires (NWs) based hybrid solar cells (HSC). This method provides a thorough insight of hybrid photovoltaic process as a function of geometrical parameters of NWs. An active layer consisting of GaAs NWs as acceptor and poly(3-hexylthiophene-2,5-diyl) (P3HT) as donor were used as a design example. Absorption spectra features were studied by the evolution of the leaky modes and Fabry-Perot resonance with wavelength focusing firstly on the GaAs/air layer before extending to GaAs/P3HT hybrid active layer. The highest absorption efficiency reached 39% for the hybrid active layer of 2 μm thickness under AM 1.5G illumination. Combined with the optical absorption analysis, our method further codesigns the energy harvesting to predict electrical performance of HSC considering exciton dissociation efficiencies within both inorganic NWs and a polymeric shell of 20 nm thickness. The validity of the simulation model was also proved by the well agreement of the simulation results with the published experimental work indicating an effective guidance for future high performance HSC design.

Minimally Invasive Distal Pancreatectomy: Review of the English Literature

Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. Nov, 2016  |  Pubmed ID: 27828724

Recently, the superiority of the minimally invasive approach, which results in a better cosmetic result, faster recovery, and shorter length of hospital stay, is a technique that has been progressively recognized as it has developed. And the minimally invasive approach has been applied to distal pancreatectomy (DP), which is a standard method for the treatment of benign, borderline, and part of malignant lesions of the pancreatic body and tail. This article aims to analyze the types, postoperative recovery, and outcomes of laparoscopic distal pancreatectomy (LDP).

Illness Perception in Chinese Adults with Epilepsy

Epilepsy Research. Oct, 2016  |  Pubmed ID: 27833067

Epilepsy is among the most common neurological disorders worldwide. Understanding the patient's subjective experience plays an important role in the treatment and rehabilitation of the patient. However, few studies are concerned about the illness perception of Chinese adults with epilepsy.

Clinicopathological and Prognostic Significance of Platelet-to-lymphocyte Ratio in Patients with Hepatocellular Carcinoma

Oncotarget. Nov, 2016  |  Pubmed ID: 27833084

The platelet-to-lymphocyte ratio (PLR) is reported to be a prognostic factor in multiple malignancies. The aim of this study was to assess its prognostic value in hepatocellular carcinoma (HCC). We performed comprehensive searches of electronic databases for relevant studies. A total of eleven studies comprising 2,507 patients were included. Elevated PLR was significantly associated with poor overall survival (OS) (HR = 1.78; 95% CI = 1.36-2.34; P < 0.001) and disease-free survival (DFS)/recurrence-free survival (RFS) (HR = 1.82; 95% CI = 1.56-2.13; P < 0.001). The findings from most subgroup analyses were consistent with those from the overall analysis. In addition, a high PLR correlated with tumor size > 3 cm, TNM stage, lymph node metastasis, distant metastasis, and vascular invasion. We therefore conclude that elevated pretreatment PLR may be predicative of a poor prognosis in patients with HCC.

Impaired White Matter Connections of the Limbic System Networks Associated with Impaired Emotional Memory in Alzheimer's Disease

Frontiers in Aging Neuroscience. 2016  |  Pubmed ID: 27833549

Background: Discrepancies persist regarding retainment of emotional enhancement of memory (EEM) in mild cognitive impairment (MCI) and early Alzheimer's disease (AD) patients.In addition, the neural mechanisms are still poorly understood, little is known about emotional memory related changes in white matter (WM). Objective: To observe whether EEM is absent in amnestic MCI (aMCI) and AD patients, and to investigate if emotional memory is associated with WM connections and gray matters (GM) of the limbic system networks. Methods: Twenty-one AD patients, 20 aMCI patients and 25 normal controls participated in emotional picture recognition tests and MRI scanning. Tract-based spatial statistics (TBSS) and voxel-based morphometry (VBM) methods were used to determine white and gray matter changes of patients. Fourteen regions of interest (ROI) of WM and 20 ROIs of GM were then selected for the correlation analyses with behavioral scores. Results: The EEM effect was lost in AD patients. Both white and gray matter of the limbic system networks were impaired in AD patients. Significant correlations or tendencies between the bilateral uncinate fasciculus, corpus callosum (genu and body), left cingulum bundle, left parahippocampal WM and the recognition sensitivity of emotional valence pictures, and significant correlations or tendencies between the splenium of corpus callosum, left cingulum bundle, left crus of fornix and stria terminalis and the recognition sensitivity of EEM were found. The volume of left amygdala, bilateral insula, medial frontal lobe, anterior and middle cingulum gyrus were positively correlated with the recognition sensitivity of emotional photos, and the right precuneus was positively correlated with the negative EEM effect. However, the affected brain areas of aMCI patients were more localized, and aMCI patients benefited only from positive stimuli. Conclusion: There are impairments of the limbic system networks of AD patients. Damaged WM connections and GM volumes of those networks are associated with impaired emotional memory and EEM effect in AD patients.

Berberine Protects Against 6-OHDA-induced Neurotoxicity in PC12 Cells and Zebrafish Through Hormetic Mechanisms Involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 Pathways

Redox Biology. Nov, 2016  |  Pubmed ID: 27835779

Berberine (BBR) is a renowned natural compound that exhibits potent neuroprotective activities. However, the cellular and molecular mechanisms are still unclear. Hormesis is an adaptive mechanism generally activated by mild oxidative stress to protect the cells from further damage. Many phytochemicals have been shown to induce hormesis. This study aims to investigate whether the neuroprotective activity of BBR is mediated by hormesis and the related signaling pathways in 6-OHDA-induced PC12 cells and zebrafish neurotoxic models. Our results demonstrated that BBR induced a typical hormetic response in PC12 cells, i.e. low dose BBR significantly increased the cell viability, while high dose BBR inhibited the cell viability. Moreover, low dose BBR protected the PC12 cells from 6-OHDA-induced cytotoxicity and apoptosis, whereas relatively high dose BBR did not show neuroprotective activity. The hormetic and neuroprotective effects of BBR were confirmed to be mediated by up-regulated PI3K/AKT/Bcl-2 cell survival and Nrf2/HO-1 antioxidative signaling pathways. In addition, low dose BBR markedly mitigated the 6-OHDA-induced dopaminergic neuron loss and behavior movement deficiency in zebrafish, while high dose BBR only slightly exhibited neuroprotective activities. These results strongly suggested that the neuroprotection of BBR were attributable to the hormetic mechanisms via activating cell survival and antioxidative signaling pathways.

A Novel Class of α-glucosidase and HMG-CoA Reductase Inhibitors from Ganoderma Leucocontextum and the Anti-diabetic Properties of Ganomycin I in KK-A(y) Mice

European Journal of Medicinal Chemistry. Nov, 2016  |  Pubmed ID: 27839787

Three new meroterpenoids, ganoleucin A-C (1-3), together with five known meroterpenoids (4-8), were isolated from the fruiting bodies of Ganoderma leucocontextum. The structures of the new compounds were elucidated by extensive spectroscopic analysis, circular dichroism (CD) spectroscopy, and chemical transformation. The inhibitory effects of 1-8 on HMG-CoA reductase and α-glucosidase were tested in vitro. Ganomycin I (4), 5, and 8 showed stronger inhibitory activity against HMG-CoA reductase than the positive control atorvastatin. Compounds 1, and 3-8 presented potent noncompetitive inhibitory activity against α-glucosidase from both yeast and rat small intestinal mucosa. Ganomycin I (4), the most potent inhibitor against both α-glucosidase and HMG-CoA reductase, was synthesized and evaluated for its in vivo bioactivity. Pharmacological results showed that ganomycin I (4) exerted potent and efficacious hypoglycemic, hypolipidemic, and insulin-sensitizing effects in KK-A(y) mice.

Experimental Realization of Entanglement in Multiple Degrees of Freedom Between Two Quantum Memories

Nature Communications. Nov, 2016  |  Pubmed ID: 27841274

Entanglement in multiple degrees of freedom has many benefits over entanglement in a single one. The former enables quantum communication with higher channel capacity and more efficient quantum information processing and is compatible with diverse quantum networks. Establishing multi-degree-of-freedom entangled memories is not only vital for high-capacity quantum communication and computing, but also promising for enhanced violations of nonlocality in quantum systems. However, there have been yet no reports of the experimental realization of multi-degree-of-freedom entangled memories. Here we experimentally established hyper- and hybrid entanglement in multiple degrees of freedom, including path (K-vector) and orbital angular momentum, between two separated atomic ensembles by using quantum storage. The results are promising for achieving quantum communication and computing with many degrees of freedom.

Multivariate Poisson Lognormal Modeling of Crashes by Type and Severity on Rural Two Lane Highways

Accident; Analysis and Prevention. Nov, 2016  |  Pubmed ID: 27846421

In an effort to improve traffic safety, there has been considerable interest in estimating crash prediction models and identifying factors contributing to crashes. To account for crash frequency variations among crash types and severities, crash prediction models have been estimated by type and severity. The univariate crash count models have been used by researchers to estimate crashes by crash type or severity, in which the crash counts by type or severity are assumed to be independent of one another and modelled separately. When considering crash types and severities simultaneously, this may neglect the potential correlations between crash counts due to the presence of shared unobserved factors across crash types or severities for a specific roadway intersection or segment, and might lead to biased parameter estimation and reduce model accuracy. The focus on this study is to estimate crashes by both crash type and crash severity using the Integrated Nested Laplace Approximation (INLA) Multivariate Poisson Lognormal (MVPLN) model, and identify the different effects of contributing factors on different crash type and severity counts on rural two-lane highways. The INLA MVPLN model can simultaneously model crash counts by crash type and crash severity by accounting for the potential correlations among them and significantly decreases the computational time compared with a fully Bayesian fitting of the MVPLN model using Markov Chain Monte Carlo (MCMC) method. This paper describes estimation of MVPLN models for three-way stop controlled (3ST) intersections, four-way stop controlled (4ST) intersections, four-way signalized (4SG) intersections, and roadway segments on rural two-lane highways. Annual Average Daily traffic (AADT) and variables describing roadway conditions (including presence of lighting, presence of left-turn/right-turn lane, lane width and shoulder width) were used as predictors. A Univariate Poisson Lognormal (UPLN) was estimated by crash type and severity for each highway facility, and their prediction results are compared with the MVPLN model based on the Average Predicted Mean Absolute Error (APMAE) statistic. A UPLN model for total crashes was also estimated to compare the coefficients of contributing factors with the models that estimate crashes by crash type and severity. The model coefficient estimates show that the signs of coefficients for presence of left-turn lane, presence of right-turn lane, land width and speed limit are different across crash type or severity counts, which suggest that estimating crashes by crash type or severity might be more helpful in identifying crash contributing factors. The standard errors of covariates in the MVPLN model are slightly lower than the UPLN model when the covariates are statistically significant, and the crash counts by crash type and severity are significantly correlated. The model prediction comparisons illustrate that the MVPLN model outperforms the UPLN model in prediction accuracy. Therefore, when predicting crash counts by crash type and crash severity for rural two-lane highways, the MVPLN model should be considered to avoid estimation error and to account for the potential correlations among crash type counts and crash severity counts.

In Vitro Anti-Inflammatory Effects of Three Fatty Acids from Royal Jelly

Mediators of Inflammation. 2016  |  Pubmed ID: 27847405

Trans-10-hydroxy-2-decenoic acid (10-H2DA), 10-hydroxydecanoic acid (10-HDAA), and sebacic acid (SEA) are the three major fatty acids in royal jelly (RJ). Previous studies have revealed several pharmacological activities of 10-H2DA and 10-HDAA, although the anti-inflammatory effects and underlying mechanisms by which SEA acts are poorly understood. In the present study, we evaluated and compared the in vitro anti-inflammatory effects of these RJ fatty acids in lipopolysaccharide-stimulated RAW 264.7 macrophages. The results showed that 10-H2DA, 10-HDAA, and SEA had potent, dose-dependent inhibitory effects on the release of the major inflammatory-mediators, nitric oxide, and interleukin-10, and only SEA decreased TNF-α production. Several key inflammatory genes have also been modulated by these RJ fatty acids, with 10-H2DA showing distinct modulating effects as compared to the other two FAs. Furthermore, we found that these three FAs regulated several proteins involved in MAPK and NF-κB signaling pathways. Taken together, these findings provide additional references for using RJ against inflammatory diseases.

Protein Ligand-specific Binding Residue Predictions by an Ensemble Classifier

BMC Bioinformatics. Nov, 2016  |  Pubmed ID: 27855637

Prediction of ligand binding sites is important to elucidate protein functions and is helpful for drug design. Although much progress has been made, many challenges still need to be addressed. Prediction methods need to be carefully developed to account for chemical and structural differences between ligands.

Adverse Events and Efficacy of Cixutumumab in Phase II Clinical Trials: A Systematic Review and Meta-Analysis

Clinical Drug Investigation. Nov, 2016  |  Pubmed ID: 27858328

Cixutumumab is a monoclonal antibody targeting insulin-like growth factor 1 receptor (IGF1R). We sought to evaluate the efficacy of cixutumumab in the treatment of cancer, and to comprehensively assess the associated adverse events in phase II clinical trials.

Modelling Seasonal Brucellosis Epidemics in Bayingolin Mongol Autonomous Prefecture of Xinjiang, China, 2010-2014

BioMed Research International. 2016  |  Pubmed ID: 27872852

Brucellosis is one of the severe public health problems; the cumulative number of new human brucellosis cases reached 211515 from 2010 to 2014 in China. Bayingolin Mongol Autonomous Prefecture is situated in the southeast of Xinjiang, where brucellosis infection occurs every year. Based on the reported data of newly acute human brucellosis cases for each season in Bayingolin Mongol Autonomous Prefecture, we proposed a susceptible, exposed, infected, and vaccinated (SEIV) model with periodic transmission rates to investigate the seasonal brucellosis transmission dynamics among sheep/cattle and from sheep/cattle to humans. Compared with the criteria of MAPE and RMSPE, the model simulations agree to the data on newly acute human brucellosis. We predict that the number of newly acute human brucellosis is increasing and will peak 15325 [95% CI: 11920-18242] around the summer of 2023. We also estimate the basic reproduction number R0 = 2.5524 [95% CI: 2.5129-2.6225] and perform some sensitivity analysis of the newly acute human brucellosis cases and the basic reproduction number R0 in terms of model parameters. Our study demonstrates that reducing the birth number of sheep/cattle, raising the slaughter rate of infected sheep/cattle, increasing the vaccination rate of susceptible sheep/cattle, and decreasing the loss rate of vaccination are effective strategies to control brucellosis epidemic.

The Yin-Yang Dynamics of DNA Methylation Is the Key Regulator for Smooth Muscle Cell Phenotype Switch and Vascular Remodeling

Arteriosclerosis, Thrombosis, and Vascular Biology. Nov, 2016  |  Pubmed ID: 27879253

DNA methylation plays an important role in chronic diseases such as atherosclerosis, yet the mechanisms are poorly understood. The objective of our study is to indicate the regulatory mechanisms of DNA methylation in vascular smooth muscle cells (VSMCs) and its roles in atherosclerosis.

Assessing Characteristics of RNA Amplification Methods for Single Cell RNA Sequencing

BMC Genomics. Nov, 2016  |  Pubmed ID: 27881084

Recently, measurement of RNA at single cell resolution has yielded surprising insights. Methods for single-cell RNA sequencing (scRNA-seq) have received considerable attention, but the broad reliability of single cell methods and the factors governing their performance are still poorly known.

Renal Denervation Attenuates Multi-Organ Fibrosis and Improves Vascular Remodeling in Rats with Transverse Aortic Constriction Induced Cardiomyopathy

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. Nov, 2016  |  Pubmed ID: 27889753

To investigate the effects of renal denervation (RDN) on multi-organ fibrosis and vascular remodeling in cardiomyopathy.

Veronicastrum Axillare Alleviates Lipopolysaccharide-Induced Acute Lung Injury Via Suppression of Proinflammatory Mediators and Downregulation of the NF-κB Signaling Pathway

Mediators of Inflammation. 2016  |  Pubmed ID: 27890971

Veronicastrum axillare is a traditional medical plant in China which is widely used in folk medicine due to its versatile biological activities, especially for its anti-inflammatory effects. However, the detailed mechanism underlying this action is not clear. Here, we studied the protective effects of V. axillare against acute lung injury (ALI), and we further explored the pharmacological mechanisms of this action. We found that pretreatment with V. axillare suppressed the release of proinflammatory cytokines in the serum of ALI mice. Histological analysis of lung tissue demonstrated that V. axillare inhibited LPS-induced lung injury, improved lung morphology, and reduced the activation of nuclear factor-κB (NF-κB) in the lungs. Furthermore, the anti-inflammatory actions of V. axillare were investigated in vitro. We observed that V. axillare suppressed the mRNA expression of interleukin-1β (IL-1β), IL-6, monocyte chemotactic protein-1 (MCP-1), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α) in RAW264.7 cells challenged with LPS. Furthermore, pretreatment of V. axillare in vitro reduced the phosphorylation of p65 and IκB-α which is activated by LPS. In conclusion, our data firstly demonstrated that the anti-inflammatory effects of V. axillare against ALI were achieved through downregulation of the NF-κB signaling pathway, thereby reducing the production of inflammatory mediators.

H2O2 And/or TiO2 Photocatalysis Under UV Irradiation for the Removal of Antibiotic Resistant Bacteria and Their Antibiotic Resistance Genes

Journal of Hazardous Materials. Feb, 2017  |  Pubmed ID: 27776873

Inactivating antibiotic resistant bacteria (ARB) and removing antibiotic resistance genes (ARGs) are very important to prevent their spread into the environment. Previous efforts have been taken to eliminate ARB and ARGs from aqueous solution and sludges, however, few satisfying results have been obtained. This study investigated whether photocatalysis by TiO2 was able to reduce the two ARGs, mecA and ampC, within the host ARB, methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, respectively. The addition of H2O2 and matrix effect on the removal of ARB and ARGs were also studied. TiO2 thin films showed great effect on both ARB inactivation and ARGs removal. Approximately 4.5-5.0 and 5.5-5.8 log ARB reductions were achieved by TiO2 under 6 and 12mJ/cm(2) UV254 fluence dose, respectively. For ARGs, 5.8 log mecA reduction and 4.7 log ampC reduction were achieved under 120mJ/cm(2) UV254 fluence dose in the presence of TiO2. Increasing dosage of H2O2 enhanced the removal efficiencies of ARB and ARGs. The results also demonstrated that photocatalysis by TiO2 was capable of removing both intracellular and extracellular forms of ARGs. This study provided a potential alternative method for the removal of ARB and ARGs from aqueous solution.

Analysis of Gene Gain and Loss in the Evolution of Predatory Bacteria

Gene. Jan, 2017  |  Pubmed ID: 27825775

Predatory bacteria are ubiquitously distributed in nature in including in aquatic environments, sewage, intestinal tracts of animals and humans, rhizophere and, soils. However, our understanding of their evolutionary history is limited. Results of recent studies have shown that acquiring novel genes is a major force driving bacterial evolution. Therefore, to gain a better understanding of the impact of gene gain and loss in the evolution of bacterial predators, this study employed comparative genomic approaches to identify core-set gene families and species-specific gene families, and model gene gain and loss events among 11 genomes that represented diverse lineages. In total, 1977 gene families were classified. Of these 509 (pattern 11111111111) were present all of the 11 species. Among the non-core set gene families, 52 were present only in saltwater bacteria predators and had no ortholog in the other genomes. Similarly 109 and 44 were present only in the genomes of Micavibrio spp. and Bdellovibrio spp., respectively. In this study, the gain loss mapping engine GLOOME was selected to analyze and estimate the expectations and probabilities of both gain and loss events in the predatory bacteria. In total, 354 gene families were involved in significant gene gain events, and 407 gene families were classified into gene loss events with high supported value. Moreover, 18 families from the core set gene family were identified as putative genes under positive selection. The results of this study suggest that acquisition of particular genes that encode functional proteins in metabolism and cellular processes and signaling, especially ABC systems, may help bacterial predators adapt to surrounding environmental changes and present different predation strategies for survival in their habitats.

Insights into Molecular Structure and Digestion Rate of Oat Starch

Food Chemistry. Apr 1 2017  |  Pubmed ID: 27855897

The in vitro digestibility of oat starch and its relationship with starch molecular structure was investigated. The in vitro digestion results showed that the first-order kinetic constant (k) of oat starches (OS-1 and OS-2) was lower than that of rice starch. The size of amylose chains, amylose content and degree of branching (DB) of amylopectin in oat starch were significantly higher than the corresponding parameters in rice starch. The larger molecular size of oat starch may account for its lower digestion rate. The fine structure of amylopectin showed that oat starch had less chains of DP 6-12 and DP>36, which may explain the small difference in digestion rate between oat and rice starch. The biosynthesis model from oat amylopectin fine structure data suggested a lower starch branching enzyme (SBE) activity and/or a higher starch synthase (SS) activity, which may decrease the DB of oat starch and increase its digestion rate.

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