In JoVE (1)

Other Publications (200)

Articles by Jing Huang in JoVE

Other articles by Jing Huang on PubMed

[Variation Characteristics of Soil Carbon Sequestration Under Long-term Different Fertilization in Red Paddy Soil]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology. Nov, 2015  |  Pubmed ID: 26915193

The objective of this study was to clarify the changes of soil organic carbon (SOC) content, the saturation capacity of soil carbon sequestration and its cooperation with carbon input (crop source and organic fertilizer source carbon) under long-term (1982-2012) different fertilization in red paddy soil. The results showed that fertilization could increase SOC content. The SOC content of all the fertilization treatments demonstrated a trend of stabilization after applying fertilizer for 30 years. The SOC content in the treatments applying organic manure with mineral fertilizers was between 21.02 and 21.24 g · kg(-1), and the increase rate ranged from 0.41 to 0.59 g · kg(-1) · a(-1). The SOC content in the treatments applying mineral fertilizers only was 15.48 g · kg(-1). The average soil carbon sequestration in the treatments that applied organic manure with mineral fertilizers ranged from 43.61 to 48.43 t C · hm(-2), and the average SOC storage over the years in these treatments was significantly greater than those applying mineral fertilizers only. There was an exponentially positive correlation between C sequestration efficiency and annual average organic C input. It must input exogenous organic carbon at least at 0. 12 t C · hm(-2) · a(-1) to maintain the balance of soil organic carbon under the experimental conditions.

Hyaluronan Synthase 2 Overexpression is Correlated with the Tumorigenesis and Metastasis of Human Breast Cancer

International Journal of Clinical and Experimental Pathology. 2015  |  Pubmed ID: 26722395

Extracellular matrix (ECM) is closely correlated with the malignant behavior of breast cancer cells. Hyaluronan (HA) is one of the main components of ECM, and actively regulates cell adhesion, migration and proliferation by interacting with specific cell surface receptors such as CD44 and RHAMM. HA synthase 2 (HAS2) catalyzes the synthesis of HA, but its role in breast tumorigenesis remains unclear. This study assessed the roles of HAS2 in malignant behavior of human breast cancer and sought to provide mechanistic insights into the biological and pivotal roles of HAS2. We observed HAS2 was overexpressed in breast cancer cell lines and invasive duct cancer tissues, compared with the nonmalignant breast cell lines and normal breast tissues. In addition, a high level of HAS2 expression was statistically correlated with lymph node metastasis. Functional assays showed that knockdown of HAS2 expression inhibited breast tumor cell proliferation in vivo and in vitro, through the induction of apoptosis or cell cycle arrest. Further studies showed that the HA were elevated in breast cancer, and HAS2 could upregulate HA expression. In conclusion, HAS2-HA system influences the biological characteristics of human breast cancer cells, and HAS2 may be a potential prognostic marker and therapeutic target in breast cancer.

[Systematic Evaluation for Efficacy of Tripterygium Glycosides in Treating Diabetic Nephropathy Stage IV]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Aug, 2015  |  Pubmed ID: 26677718

To systematically evaluate the efficacy and safety of tripterygium glycosides (TG) combined with ACEI/ARB preparation in treating diabetic nephropathy stage IV. The computer retrievals were made in Cochrane Libarary, PubMed, Embase, SCI, Sinnomed, CNKI, Chinainfo and VIP, and hand retrievals were conducted for meeting and academic papers (updated to December 30, 2014), in order to collect randomized controlled trials and quasi-randomized control trials for TG combined with ACEI/ARB preparation in treating diabetic nephropathy stage IV and set the literature inclusion and elimination standards. Eligible literatures were included and evaluated according to standards in Cochrane Handbook. RevMan 5.3 and Stata 12.0 were used for a Meta-analysis. A total of 13 randomized controlled trials and quasi-randomized control trials involving 1119 patients with diabetic nephropathy were included. The Meta analysis result showed that compared with the control group, the combination group showed better effects in reducing the 24-hour urinary protein [MD = -0.84, 95% CI (-1.02, -0.66)], raising albumin [SMD = 0.98, 95% CI (0.81, 1.16)], the total efficiency [OR = 4.23, 95% CI (2.77, 6.46)] and the significant efficiency [OR = 5.35, 95% CI (2.70, 10.60)], with no statistical difference in Serum Creatinine between Both groups [MD = -0.82, 95% CI (-4.30, 2.66), P = 0.64]. However, the risk of adverse reactions increased by 7% [RD = 0.07, 95% CI (0.03, 0.12)]. The Egger's test showed no publication bias. Tripterygium Glycosides combined with ACEI/ARB in treating diabetic nephropathy stage IV is supper than the single administration of ACEI/ARB, with a good prospect in clinical application. Nevertheless, due to the small-size and low-quality samples in this study, more high-quality and large sample-size randomized controlled trials shall be conducted to verify the findings.

Effects of Ligustrum Robustum on Gut Microbes and Obesity in Rats

World Journal of Gastroenterology. Dec, 2015  |  Pubmed ID: 26676281

To investigate the anti-obesity and antibacterial effects of Ligustrum robustum (L. robustum) in vivo and in vitro and its possible mechanisms.

[Analysis About the High Risk Factors and Prognosis of Gynecologic Cancer with Deep Venous Thrombosis]

Zhonghua Fu Chan Ke Za Zhi. Oct, 2015  |  Pubmed ID: 26675576

To discuss the risk factors and prognosis of gynecologic cancer patients with deep venous thrombosis (DVT).

Microarray Analysis Unmasked Two Siblings with Pure Hereditary Spastic Paraplegia Shared a Run of Homozygosity Region on Chromosome 3q28-q29

Journal of the Neurological Sciences. Dec, 2015  |  Pubmed ID: 26671141

Hereditary spastic paraplegia (HSP) is a clinical and genetic heterogeneity group of neurodegenerative disorders which is characterized by progressive weakness and spasticity of the lower limbs. More than 70 genetic types of HSP have been described so far. Here we describe a Chinese non-consanguineous family with two affected siblings manifesting early-onset autosomal recessive HSP in pure forms. To identify genotype and characterize phenotype, CytoScan HD array analysis was performed on the two siblings. A run of homozygosity (ROH) shared by the two patients was detected on chromosome 3q28-q29. The ROH region, about 7.7Mb on the chromosome 3:190172058-197851260 partially overlapped with the ROH region of SPG14 previously reported. Subsequently, microsatellite analysis confirmed this ROH and whole-exome sequencing was carried out while no causative mutations were found in the exons of known HSP genes and 68 candidate genes in that region. In conclusion, our data suggest the ROH in this region may play a pivotal role in SPG14 pathogenesis. This is the first clinical description of a pure form spastic paraplegia in a non-consanguineous family associated with the SPG14 locus.

Nurse-led Intensive Interventions Improve Adherence to Continuous Positive Airway Pressure Therapy and Quality of Life in Obstructive Sleep Apnea Patients

Patient Preference and Adherence. 2015  |  Pubmed ID: 26648703

Continuous positive airway pressure (CPAP) is widely recommended for the treatment of sleep apnea/hypopnea syndrome (SAHS), but its usage by patients is very low. The aim of this study was to assess intensive educational programs and nursing support for the improvement of CPAP use and outcomes in SAHS patients.

Induced Dipole-Dipole Interactions Influence the Unfolding Pathways of Wild-Type and Mutant Amyloid β-Peptides

The Journal of Physical Chemistry. B. Dec, 2015  |  Pubmed ID: 26629591

Amyloid-forming proteins undergo a structural transition from α-helical to disordered conformations and, ultimately, cross-β fibrils. The unfolding and aggregation of the amyloid β-peptide (Aβ) have been implicated in the development and progression of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). However, the events underlying the initial structural transition leading to the disease state remain unclear. Although most cases are sporadic, several genetic variants exist that alter the electrostatic properties of Aβ and lead to more rapid unfolding and more severe phenotypes. In the present study, the enhanced unfolding is shown to be due to the mutated side chains altering the local peptide-bond dipole moments leading to local destabilization of the α-helix, as determined from polarizable molecular dynamics (MD) simulations of wild-type (WT) Aβ fragments and several common mutations. The local perturbation of the helix then leads to progressive unwinding of the α-helix in a cooperative fashion due to decreases in adjacent (i ± 1) and hydrogen-bonded (i + 4) peptide-bond dipole moments. Side-chain dynamics, subsequent variations in dipole moments, and ultimately the response in the peptide-bond dipole moments are all modulated by solvent dielectric properties based on simulations in water versus ethanol. The polarizable simulation results, along with simulations using the additive CHARMM36 force field, further indicate that cooperativity due to the alignment of peptide bonds leading to enhanced dipole moments is a fundamental force in stabilizing α-helices.

Relief of Diabetes by Duodenal-jejunal Bypass Sleeve Implantation in the High-fat Diet and Streptozotocin-induced Diabetic Rat Model is Associated with an Increase in GLP-1 Levels and the Number of GLP-1-positive Cells

Experimental and Therapeutic Medicine. Oct, 2015  |  Pubmed ID: 26622491

A recently invented duodenal-jejunal bypass sleeve (DJBS) implanted in the duodenum and proximal jejunum has exhibited good glycemic control in diabetes mellitus. However, the specific mechanism by which DJBS placement induces the remission of diabetes is not well known. Previous studies have indicated that changes in the pattern of gut hormone secretion may play a role. The aim of the present study was to explore the role of intestinal L cells and the production of glucagon-like peptide-1 (GLP-1) by these cells in DJBS implantation-induced glycemic control in diabetic rats. A DJBS was placed in the proximal small intestine of rats with diabetes induced by a high-fat diet and low-dose streptozotocin (STZ), and the effects of the DJBS on the remission of diabetes and the GLP-1 levels of plasma and intestinal tissues were investigated 12 weeks after DJBS placement. The number of intestinal GLP-1 positive cells was also counted. When the DJBS had been in place for 12 weeks, the plasma glucose level of the DJBS-implanted rats decreased significantly from 23.33±1.56 mmol/l prior to surgery to 7.70±0.84 mmol/l and the diabetes mellitus was relieved completely; however, diabetic control rats and diabetic rats subjected to sham surgery did not show any improvement. Parallel with the remission of diabetes, the plasma and distal ileum GLP-1 levels of rats in the DJBS implantation group were also higher than those of rats in the diabetic control and sham surgery groups. The number of GLP-1-positive cells in the distal ileum was also higher in the DJBS implantation group than in the diabetic control and sham surgery groups (31.0±2.6 vs. 23.5±4.4 vs. 23.0±3.2 respectively; P<0.01). DJBS implantation effectively led to the remission of diabetes in rats with diabetes induced by a high-fat diet and low-dose STZ when implanted for 12 weeks. The remission of diabetes may be associated with the increase in the number of L cells and elevation of GLP-1 levels induced by DJBS implantation.

Monte Carlo Dosimetry of a New (90)Y Brachytherapy Source

Journal of Contemporary Brachytherapy. Oct, 2015  |  Pubmed ID: 26622247

In this study, we attempted to obtain full dosimetric data for a new (90)Y brachytherapy source developed by the College of Chemistry (Sichuan University) for use in high-dose-rate after-loading systems.

[Robust Low-dose CT Myocardial Perfusion Deconvolution Via High-dimension Total Variation Regularization]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Nov, 2015  |  Pubmed ID: 26607079

To develop a computed tomography myocardial perfusion (CT-MP) deconvolution algorithm by incorporating high-dimension total variation (HDTV) regularization.

PEG-b-AGE Polymer Coated Magnetic Nanoparticle Probes with Facile Functionalization and Anti-fouling Properties for Reducing Non-specific Uptake and Improving Biomarker Targeting

Journal of Materials Chemistry. B, Materials for Biology and Medicine. May, 2015  |  Pubmed ID: 26594360

Non-specific surface adsorption of bio-macromolecules (e.g. proteins) on nanoparticles, known as biofouling, and the uptake of nanoparticles by the mononuclear phagocyte system (MPS) and reticuloendothelial system (RES) lead to substantial reduction in the efficiency of target-directed imaging and delivery in biomedical applications of engineered nanomaterials in vitro and in vivo. In this work, a novel copolymer consisting of blocks of poly ethylene glycol and allyl glycidyl ether (PEG-b-AGE) was developed for coating magnetic iron oxide nanoparticles (IONPs) to reduce non-specific protein adhesion that leads to formation of "protein corona" and uptake by macrophages. The facile surface functionalization was demonstrated by using targeting ligands of a small peptide of RGD or a whole protein of transferrin (Tf). The PEG-b-AGE coated IONPs exhibited anti-biofouling properties with significantly reduced protein corona formation and non-specific uptake by macrophages before and after the surface functionalization, thus improving targeting of RGD-conjugated PEG-b-AGE coated IONPs to integrins in U87MG glioblastoma and MDA-MB-231 breast cancer cells that overexpress αvβ3 integrins, and Tf-conjugated PEG-b-AGE coated IONPs to transferrin receptor (TfR) in D556 and Daoy medulloblastoma cancer cells with high overexpression of transferrin receptor, compared to respective control cell lines. Magnetic resonance imaging (MRI) of cancer cells treated with targeted IONPs with or without anti-biofouling PEG-b-AGE coating polymers demonstrated the target specific MRI contrast change using anti-biofouling PEG-b-AGE coated IONP with minimal off-targeted background compared to the IONPs without anti-biofouling coating, promising the highly efficient active targeting of nanoparticle imaging probes and drug delivery systems and potential applications of imaging quantification of targeted biomarkers.

[Effect of Four Kinds of Drinking Water on Hepatic and Renal Function and Zinc and Iron Concentrations of Different Organs in Mice]

Wei Sheng Yan Jiu = Journal of Hygiene Research. Sep, 2015  |  Pubmed ID: 26591779

To explore the effect of different drinking water on hepatic and renal function and zinc and iron concentrations of different organs in mice.

High Quality Draft Genome Sequence of the Moderately Halophilic Bacterium Pontibacillus Yanchengensis Y32(T) and Comparison Among Pontibacillus Genomes

Standards in Genomic Sciences. 2015  |  Pubmed ID: 26561516

Pontibacillus yanchengensis Y32(T) is an aerobic, motile, Gram-positive, endospore-forming, and moderately halophilic bacterium isolated from a salt field. In this study, we describe the features of P. yanchengensis strain Y32(T) together with a comparison with other four Pontibacillus genomes. The 4,281,464 bp high-quality-draft genome of strain Y32(T) is arranged into 153 contigs containing 3,965 protein-coding genes and 77 RNA encoding genes. The genome of strain Y32(T) possesses many genes related to its halophilic character, flagellar assembly and chemotaxis to support its survival in a salt-rich environment.

Renal Interstitial Arteriosclerotic Lesions in Lupus Nephritis Patients: A Cohort Study from China

PloS One. 2015  |  Pubmed ID: 26544865

The aim of this study was to evaluate renal arteriosclerotic lesions in patients with lupus nephritis and investigate their associations with clinical and pathological characteristics, especially cardio-vascular features.

An Easy Method for Preparation of Cre-loxP Regulated Fluorescent Adenoviral Expression Vectors and Its Application for Direct Reprogramming into Hepatocytes

Biotechnology Reports (Amsterdam, Netherlands). Dec, 2016  |  Pubmed ID: 28352551

The recombinant adenoviral gene expression system is a powerful tool for gene delivery. However, it is difficult to obtain high titers of infectious virus, principally due to the toxicity of the expressed gene which affects on virus replication in the host HEK293 cells. To avoid these problems, we generated a Cre-loxP-regulated fluorescent universal vector (termed pAxCALRL). This vector produces recombinant adenoviruses that express the red fluorescent protein (RFP) instead of the inserted gene during proliferation, which limits toxicity and can be used to monitor viral replication. Expression of the gene of interest is induced by co-infection with an adenovirus that expresses Cre-recombinase (AxCANCre). Recombinant adenovirus produced by this system that express Hnf4α and Foxa2 were used to reprogram mouse embryo fibroblast (MEF) into induced-hepatocyte-like cells (iHep) following several rounds of infection, demonstrating the efficacy of this new system.

An Empirical Study for Impacts of Measurement Errors on EHR Based Association Studies

AMIA ... Annual Symposium Proceedings. AMIA Symposium. 2016  |  Pubmed ID: 28269935

Over the last decade, Electronic Health Records (EHR) systems have been increasingly implemented at US hospitals. Despite their great potential, the complex and uneven nature of clinical documentation and data quality brings additional challenges for analyzing EHR data. A critical challenge is the information bias due to the measurement errors in outcome and covariates. We conducted empirical studies to quantify the impacts of the information bias on association study. Specifically, we designed our simulation studies based on the characteristics of the Electronic Medical Records and Genomics (eMERGE) Network. Through simulation studies, we quantified the loss of power due to misclassifications in case ascertainment and measurement errors in covariate status extraction, with respect to different levels of misclassification rates, disease prevalence, and covariate frequencies. These empirical findings can inform investigators for better understanding of the potential power loss due to misclassification and measurement errors under a variety of conditions in EHR based association studies.

A Pilot Phase II Study of Neoadjuvant Triplet Chemotherapy Regimen in Patients with Locally Advanced Resectable Colon Cancer

Chinese Journal of Cancer Research = Chung-kuo Yen Cheng Yen Chiu. Dec, 2016  |  Pubmed ID: 28174488

This study aims to investigate the feasibility, safety and efficacy of triplet regimen of neoadjuvant chemotherapy in patients with locally advanced resectable colon cancer.

Hematological Disorders and Pulmonary Hypertension

World Journal of Cardiology. Dec, 2016  |  Pubmed ID: 28070238

Pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate, is known to occur in a number of unrelated systemic diseases. Several hematological disorders such as sickle cell disease, thalassemia and myeloproliferative diseases develop PH which worsens the prognosis. Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction. Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity, activation of proliferative and antiapoptotic pathways leading to vascular remodeling, elevated pulmonary artery pressure, right ventricular hypertrophy and premature death. Hemolysis observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide (NO), limiting its bioavailability, and leading to endothelial dysfunction. In addition, hemolysis releases arginase into the circulation which converts L-arginine to ornithine, thus bypassing NO production. Furthermore, treatments for hematological disorders such as immunosuppressive therapy, splenectomy, bone marrow transplantation, and radiation have been shown to contribute to the development of PH. Recent studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension (PAH). Several studies have reported low iron levels in patients with idiopathic PAH, and iron deficiency is an important risk factor. This article reviews PH associated with hematological disorders and its mechanism; and iron homeostasis and its relevance to PH.

Bloom Syndrome Complex Promotes FANCM Recruitment to Stalled Replication Forks and Facilitates Both Repair and Traverse of DNA Interstrand Crosslinks

Cell Discovery. 2016  |  Pubmed ID: 28058110

The recruitment of FANCM, a conserved DNA translocase and key component of several DNA repair protein complexes, to replication forks stalled by DNA interstrand crosslinks (ICLs) is a step upstream of the Fanconi anemia (FA) repair and replication traverse pathways of ICLs. However, detection of the FANCM recruitment has been technically challenging so that its mechanism remains exclusive. Here, we successfully observed recruitment of FANCM at stalled forks using a newly developed protocol. We report that the FANCM recruitment depends upon its intrinsic DNA translocase activity, and its DNA-binding partner FAAP24. Moreover, it is dependent on the replication checkpoint kinase, ATR; but is independent of the FA core and FANCD2-FANCI complexes, two essential components of the FA pathway, indicating that the FANCM recruitment occurs downstream of ATR but upstream of the FA pathway. Interestingly, the recruitment of FANCM requires its direct interaction with Bloom syndrome complex composed of BLM helicase, Topoisomerase 3α, RMI1 and RMI2; as well as the helicase activity of BLM. We further show that the FANCM-BLM complex interaction is critical for replication stress-induced FANCM hyperphosphorylation, for normal activation of the FA pathway in response to ICLs, and for efficient traverse of ICLs by the replication machinery. Epistasis studies demonstrate that FANCM and BLM work in the same pathway to promote replication traverse of ICLs. We conclude that FANCM and BLM complex work together at stalled forks to promote both FA repair and replication traverse pathways of ICLs.

The Role of Omega-3 Polyunsaturated Fatty Acids in Heart Failure: A Meta-Analysis of Randomised Controlled Trials

Nutrients. Dec, 2016  |  Pubmed ID: 28042816

Many new clinical trials about the effect of omega-3 polyunsaturated fatty acids (PUFAs) in heart failure (HF) patients have shown inconsistent results. Therefore, a meta-analysis of randomised controlled trials (RCTs) was performed to determine the benefits of omega-3 PUFAs in HF patients. Articles were obtained from PubMed, EMBASE, and the Cochrane Library. RCTs comparing omega-3 PUFAs with placebo for HF were included. Two reviewers independently extracted the data from the selected publications. The I² statistic was used to assess heterogeneity. The pooled mean difference and associated 95% confidence intervals were calculated, and a fixed or random-effects model was used for the meta-analysis. A total of nine RCTs involving 800 patients were eligible for inclusion. Compared with patients taking placebo, HF patients who received omega-3 PUFAs experienced decreased brain natriuretic peptide levels and serum norepinephrine levels. Although the left ventricular ejection fraction (LVEF) and clinical outcomes (Tei index, peak oxygen consumption) did not improve, subgroup analysis showed that the LVEF increased in dilated cardiomyopathy (DCM) patients. Overall, omega-3 PUFA supplements might be beneficial in HF patients, especially in DCM patients, but further studies are needed to confirm these benefits.

Pseudaminobacter Manganicus Sp. Nov., Isolated from Sludge of a Manganese Mine

International Journal of Systematic and Evolutionary Microbiology. Dec, 2016  |  Pubmed ID: 28036252

A Gram-staining-negative, aerobic, non-motile, capsule-forming and rod-shaped bacterium, designated JH-7T, was isolated from sludge of a manganese mine. The 16S rRNA gene sequence of strain JH-7T showed highest similarities to Pseudaminobacter salicylatoxidans BN12T (97.4 %), Mesorhizobium thiogangeticum SJTT (97.0 %) and Pseudaminobacter defluvii THI 051T (96.5 %). Phylogenetic trees clustered strain JH-7T together with P. salicylatoxidans BN12T and P. defluvii THI 051T. The DNA-DNA hybridization values between strain JH-7T and P. salicylatoxidans DSM 6986T and between strain JH-7T and M. thiogangeticum DSM 17097T were 34.8 % and 20.1 %, respectively. The major fatty acids of strain JH-7T (> 10 %) were C18:1 ω7c, C19:0 cyclo ω8c and C16:0. The genomic DNA G+C content was 61.6 mol%. The polyamines of strain JH-7T were sym-homospermidine (83 %) and putrescine (17 %), and the respiratory quinone was ubiquinone-10. The major polar lipids were phosphatidylmonomethylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, two unidentified aminolipids and two unidentified lipids. Compared to the Pseudaminobacter and Mesorhizobium members, strain JH-7T showed some unique physiological and biochemical characters, such as negative in H2S production, hydrolysis of Tween 40 and Tween 60, esterase lipase (C8) activity and assimilation of D-ribose, and positive in acid production from D-galactose and assimilation of D-fructose. On the basis of the polyphasic taxonomic analysis, strain JH-7T was considered to represent a novel species of the genus Pseudaminobacter, for which the name Pseudaminobacter manganicus sp. nov. is proposed. The type strain is JH-7T (= KCTC 52258T = CCTCC AB 2016107T).

Efficiency of Emission Control Measures on Particulate Matter-Related Health Impacts and Economic Cost During the 2014 Asia-Pacific Economic Cooperation Meeting in Beijing

International Journal of Environmental Research and Public Health. Dec, 2016  |  Pubmed ID: 28036006

Background: The Asia-Pacific Economic Cooperation (APEC) meeting was held from 5 November to 11 November 2014 in Beijing, and comprehensive emission control measures were implemented. The efficiency of these measures on particulate matter-related health impacts and economic cost need to be evaluated. Methods: The influences of emission control measures during APEC on particulate matter were evaluated, and health economic effects were assessed. Results: Average concentrations of PM2.5 and PM10 during APEC were reduced by 57.0%, and 50.6% respectively, compared with pre-APEC period. However, the concentrations of particulate matter rebounded after APEC. Compared with the pre-APEC and post-APEC periods, the estimated number of deaths caused by non-accidental, cardiovascular and respiratory diseases that could be attributed to PM2.5 and PM10 during the APEC were the lowest. The economic cost associated with mortality caused by PM2.5 and PM10 during the APEC were reduced by (61.3% and 66.6%) and (50.3% and 60.8%) respectively, compared with pre-APEC and post-APEC. Conclusions: The emission control measures were effective in improving short term air quality and reducing health risks and medical expenses during 2014 APEC, but more efforts is needed for long term and continuous air quality improvement and health protection.

Gas Exchange in Fruits Related to Skin Condition and Fruit Ripening Studied with Diode Laser Spectroscopy

Journal of Biomedical Optics. Dec, 2016  |  Pubmed ID: 28008448

Cyclooxygenase-2 in Tumor-associated Macrophages Promotes Metastatic Potential of Breast Cancer Cells Through Akt Pathway

International Journal of Biological Sciences. 2016  |  Pubmed ID: 27994517

Tumor-associated macrophages (TAMs) promote cancer development and progression by releasing various cytokines and chemokines. Previously, we have found that the number of COX-2(+) TAMs was associated with lymph node metastasis in breast cancer. However, the mechanism remains enigmatic. In this study, we show that COX-2 in breast TAMs enhances the metastatic potential of breast cancer cells. COX-2 in TAMs induces MMP-9 expression and promotes epithelial-mesenchymal transition (EMT) in breast cancer cells. In addition, COX-2/PGE2 induces IL-6 release in macrophages. Furthermore, we find that the activation of Akt pathway in cancer cells is crucial for the pro-metastatic effect of COX-2(+) TAMs by regulating MMP-9 and EMT. These findings indicate that TAMs facilitate breast cancer cell metastasis through COX-2-mediated intercellular communication.

Aligning Metabolic Pathways Exploiting Binary Relation of Reactions

PloS One. 2016  |  Pubmed ID: 27936108

Metabolic pathway alignment has been widely used to find one-to-one and/or one-to-many reaction mappings to identify the alternative pathways that have similar functions through different sets of reactions, which has important applications in reconstructing phylogeny and understanding metabolic functions. The existing alignment methods exhaustively search reaction sets, which may become infeasible for large pathways. To address this problem, we present an effective alignment method for accurately extracting reaction mappings between two metabolic pathways. We show that connected relation between reactions can be formalized as binary relation of reactions in metabolic pathways, and the multiplications of zero-one matrices for binary relations of reactions can be accomplished in finite steps. By utilizing the multiplications of zero-one matrices for binary relation of reactions, we efficiently obtain reaction sets in a small number of steps without exhaustive search, and accurately uncover biologically relevant reaction mappings. Furthermore, we introduce a measure of topological similarity of nodes (reactions) by comparing the structural similarity of the k-neighborhood subgraphs of the nodes in aligning metabolic pathways. We employ this similarity metric to improve the accuracy of the alignments. The experimental results on the KEGG database show that when compared with other state-of-the-art methods, in most cases, our method obtains better performance in the node correctness and edge correctness, and the number of the edges of the largest common connected subgraph for one-to-one reaction mappings, and the number of correct one-to-many reaction mappings. Our method is scalable in finding more reaction mappings with better biological relevance in large metabolic pathways.

RECQL5 Plays Co-operative and Complementary Roles with WRN Syndrome Helicase

Nucleic Acids Research. Dec, 2016  |  Pubmed ID: 27923933

Direct Regulation of Alternative Splicing by SMAD3 Through PCBP1 Is Essential to the Tumor-Promoting Role of TGF-β

Molecular Cell. Dec, 2016  |  Pubmed ID: 27912093

Differential Efficacy of Methylcobalamin and Alpha-lipoic Acid Treatment on Negative and Positive Symptoms of (type 2) Diabetic Peripheral Neuropathy

Minerva Endocrinologica. Nov, 2016  |  Pubmed ID: 27901334

Diabetic hyperglycemia damages peripheral nerves by triggering ischemia, oxidative stress, and inflammation. Alpha-lipoic acid (ALA) and methylcobalamin (MC) are known to improve signs of diabetic peripheral neuropathy (DPN), possibly by enhancing neural and vascular endothelial cell metabolism and antioxidant capacity. We evaluated differences in efficacy following short-term MC or ALA treatment on DPN symptoms to guide clinical drug selection.

A Cognitive Model Based on Neuromodulated Plasticity

Computational Intelligence and Neuroscience. 2016  |  Pubmed ID: 27872638

Associative learning, including classical conditioning and operant conditioning, is regarded as the most fundamental type of learning for animals and human beings. Many models have been proposed surrounding classical conditioning or operant conditioning. However, a unified and integrated model to explain the two types of conditioning is much less studied. Here, a model based on neuromodulated synaptic plasticity is presented. The model is bioinspired including multistored memory module and simulated VTA dopaminergic neurons to produce reward signal. The synaptic weights are modified according to the reward signal, which simulates the change of associative strengths in associative learning. The experiment results in real robots prove the suitability and validity of the proposed model.

MHC Class II Risk Alleles and Amino Acid Residues in Idiopathic Membranous Nephropathy

Journal of the American Society of Nephrology : JASN. Nov, 2016  |  Pubmed ID: 27852637

Epitopes of phospholipase A2 receptor (PLA2R), the target antigen in idiopathic membranous nephropathy (iMN), must be presented by the HLA-encoded MHC class II molecules to stimulate autoantibody production. A genome-wide association study identified risk alleles at HLA and PLA2R loci, with the top variant rs2187668 within HLA-DQA1 showing a risk effect greater than that of the top variant rs4664308 within PLA2R1. How the HLA risk alleles affect epitope presentation by MHC class II molecules in iMN is unknown. Here, we genotyped 261 patients with iMN and 599 healthy controls at the HLA-DRB1, HLA-DQA1, HLA-DQB1, and HLA-DPB1 loci with four-digit resolution and extracted the encoded amino acid sequences from the IMGT/HLA database. We predicted T cell epitopes of PLA2R and constructed MHC-DR molecule-PLA2R peptide-T cell receptor structures using Modeler. We identified DRB1*1501 (odds ratio, 4.65; 95% confidence interval [95% CI], 3.39 to 6.41; P<0.001) and DRB1*0301 (odds ratio, 3.96; 95% CI, 2.61 to 6.05; P<0.001) as independent risk alleles for iMN and associated with circulating anti-PLA2R antibodies. Strong gene-gene interaction was noted between rs4664308(AA) and HLA-DRB1*1501/DRB1*0301. Amino acid positions 13 (P<0.001) and 71 (P<0.001) in the MHC-DRβ1 chain independently associated with iMN. Structural models showed that arginine13 and alanine71, encoded by DRB1*1501, and lysine71, encoded by DRB1*0301, facilitate interactions with T cell epitopes of PLA2R. In conclusion, we identified two risk alleles of HLA class II genes and three amino acid residues on positions 13 and 71 of the MHC-DRβ1 chain that may confer susceptibility to iMN by presenting T cell epitopes on PLA2R.

An Integrated Intervention for Increasing Clinical Nurses' Knowledge of HIV/AIDS-Related Occupational Safety

International Journal of Environmental Research and Public Health. Nov, 2016  |  Pubmed ID: 27828002

Background: Approximately 35 new HIV (Human Immunodeficiency Virus, HIV) cases and at least 1000 serious infections are transmitted annually to health care workers. In China, HIV prevalence is increasing and nursing personnel are encountering these individuals more than in the past. Contaminated needle-stick injuries represent a significant occupational burden for nurses. Evidence suggests that nurses in China may not fully understand HIV/AIDS (Acquired immunodeficiency syndrome, AIDS) and HIV-related occupational safety. At this time, universal protection precautions are not strictly implemented in Chinese hospitals. Lack of training may place nurses at risk for occupational exposure to blood-borne pathogens. Objectives: To assess the effectiveness of integrated interventions on nurses' knowledge improvement about reducing the risk of occupationally acquired HIV infection. Methods: We audited integrated interventions using 300 questionnaires collected from nurses at the Affiliated Hospital of Xiangnan University, a public polyclinic in Hunan Province. The intervention studied was multifaceted and included appropriate and targeted training content for hospital, department and individual levels. After three months of occupational safety integrated interventions, 234 participants who completed the program were assessed. Results: Of the subjects studied, 94.3% (283/300) were injured one or more times by medical sharp instruments or splashed by body fluids in the last year and 95.3% considered their risk of occupational exposure high or very high. After the intervention, awareness of HIV/AIDS-related knowledge improved significantly (χ² = 86.34, p = 0.00), and correct answers increased from 67.9% to 82.34%. Correct answers regarding risk perception were significantly different between pre-test (54.4%) and post-test (66.6%) (χ² = 73.2, p = 0.00). When coming into contact with patient body fluids and blood only 24.0% of subjects used gloves regularly. The pre-test knowledge scores on universal precautions were relatively high. Correct answers about universal precautions improved significantly from pre-test (83.71%) to post-test (89.58%; χ² = 25.00, p = 0.00). After the intervention, nurses' attitude scores improved significantly from pre-test (3.80 ± 0.79) to post-test (4.06 ± 0.75; t = 3.74, p = 0.00). Conclusions: Integrated educational interventions enhance nurses' knowledge of risk reduction for occupationally acquired HIV infections and improve the observance of universal precautionary procedures. This enhancement allows nurses to assume a teaching role for prevention and management of HIV/AIDS.

ANGPTL8 Reverses Established Adriamycin Cardiomyopathy by Stimulating Adult Cardiac Progenitor Cells

Oncotarget. Dec, 2016  |  Pubmed ID: 27823982

Established adriamycin cardiomyopathy is a lethal disease. When congestive heart failure develops, mortality is approximately 50% in a year. It has been known that ANGPTLs has various functions in lipid metabolism, inflammation, cancer cell invasion, hematopoietic stem activity and diabetes. We hypothesized that ANGPTL8 is capable of maintaining heart function by stimulating adult cardiac progenitor cells to initiate myocardial regeneration. We employed UTMD to deliver piggybac transposon plasmids with the human ANGPTL8 gene to the liver of rats with adriamycin cardiomyopathy. After ANGPTL8 gene liver delivery, overexpression of transgenic human ANGPTL8 was found in rat liver cells and blood. UTMD- ANGPTL8 gene therapy restored LV mass, fractional shortening index, and LV posterior wall diameter to nearly normal. Our results also showed that ANGPTL8 reversed established ADM cardiomyopathy. This was associated with activation of ISL-1 positive cardiac progenitor cells in the epicardium. A time-course experiment shown that ISL-1 cardiac progenitor cells proliferated and formed a niche in the epicardial layer and then migrated into sub-epicardium. The observed myocardial regeneration accompanying reversal of adriamycin cardiomyopathy was associated with upregulation of PirB expression on the cell membrane of cardiac muscle cells or progenitor cells stimulated by ANGPTL8.

[Clinical Effect of High-frequency Oscillatory Ventilation Combined with Pulmonary Surfactant in Treatment of Neonatal Severe Meconium Aspiration Syndrome Complicated by Pulmonary Hemorrhage]

Zhongguo Dang Dai Er Ke Za Zhi = Chinese Journal of Contemporary Pediatrics. Nov, 2016  |  Pubmed ID: 27817768

To study the clinical effect and safety of high-frequency oscillatory ventilation (HFOV) combined with pulmonary surfactant (PS) in the treatment of neonatal severe meconium aspiration syndrome (MAS) complicated by neonatal pulmonary hemorrhage (NPH).

Clinical Feasibility of a New Method to Identify Chronotropic Incompetence in Heart Failure Patients

Physiological Measurement. Nov, 2016  |  Pubmed ID: 27754982

Heart failure patients have a high incidence of chronotropic incompetence (CI) that receives less clinical attention. This study assessed a method using wearable devices to identify CI in heart failure patients. Twenty-six heart failure patients (LVEF: 43.9  ±  5.7% with LVEF  ⩾40% in 19 patients; age: 52.8  ±  12.4 years, female patients  =  6) were enrolled. Each patient underwent symptom-limited treadmill maximal exercise testing during which the simultaneous recording of ECG Holter and physical activity using Actigraph was conducted. The APMHR ratio, the maximal heart rate during peak exercise over the age-predicted maximal heart rate (APMHR, 220-age), was determined. CI was diagnosed in patients who failed to reach at least 0.70 APMHR ratio. Holter-Actigraph recording was also applied during a 6 min hall walk (6MHW) and for 24 h to validate the method to assess impaired chronotropic response. Based on the reports of exercise testing in 26 patients, 13 patients (50%) failed to reach at least 0.70 APMHR ratio while the remaining 13 patients achieved  ⩾0.70 APMHR ratio. The APMHR ratio measured by Holter-Actigraph recording was significantly correlated with the APMHR ratio based on exercise test reports (R  =  0.99, P  <  0.001). The cut-off values of APMHR ratio (0.65) measured during 6MHW, APMHR ratio (0.69) measured during daily activities, and maximum Δ heart rate (37.8 bpm) measured during daily activities significantly predicted the results of exercise test reports with an area under the ROC curve of 0.7337, 0.7544 and 0.7870, respectively (all P values  <  0.05). This pilot study found that the wearable device can potentially help in the identification of chronotropic incompetence in heart failure patients.

Extraction, Purification, Characterization and Antioxidant Activities of Polysaccharides from Cistanche Tubulosa

International Journal of Biological Macromolecules. Dec, 2016  |  Pubmed ID: 27593241

An efficient ultrasonic-cellulase-assisted extraction (UCE) of Cistanche tubulosa polysaccharide (CTP) was established. The response surface methodology based on Box-Behnken Design was employed to further optimize extraction conditions. After quaternary ammonium salt precipitation, the polysaccharide of C. tubulosa was characterized by different techniques. The results showed that a maximum polysaccharide yield of 22.31±0.45% was achieved at a pH of 5.2 for 31.5min at 54.1°C. Compared to hot water extraction, the yield of CTP in UCE and polysaccharide content increased to 44.96% and 70.13±2.19%, respectively. There was no marked difference among polysaccharides extracted using different methods from the infrared spectrum. Ultrasonic-cellulase-assisted extraction polysaccharide showed a fibrous structure from scanning electron microscopy and was composed of rhamnose, mannose, glucose, and galactose in a molar ratio of 2.18:1:28.29:1.43 by gas chromatography. The circular dichroism results indicated that polysaccharides had a maximum positive peak around 210nm with different peak values. The thermogravimetric analysis and differential scanning calorimetry were used to test the thermostability of CTP. Besides, CTP demonstrated appreciable antioxidant potential on antioxidant experiments in vitro. The results suggested that UCE is an effective method for CTP extraction and its polysaccharide showed appreciable antioxidant activity.

Vitamin D Receptor Down-Regulation Is Associated With Severity of Albuminuria in Type 2 Diabetes Patients

The Journal of Clinical Endocrinology and Metabolism. Nov, 2016  |  Pubmed ID: 27552538

Inflammation plays an important role in albuminuria in type 2 diabetes mellitus (T2DM). The vitamin D receptor (VDR) has potent anti-inflammatory activities.

Vertical Transmission of Zika Virus in Aedes Aegypti Mosquitoes

The American Journal of Tropical Medicine and Hygiene. Nov, 2016  |  Pubmed ID: 27573623

Previous experimental studies have demonstrated that a number of mosquito-borne flavivirus pathogens are vertically transmitted in their insect vectors, providing a mechanism for these arboviruses to persist during adverse climatic conditions or in the absence of a susceptible vertebrate host. In this study, designed to test whether Zika virus (ZIKV) could be vertically transmitted, female Aedes aegypti and Aedes albopictus were injected with ZIKV, and their F1 adult progeny were tested for ZIKV infection. Six of 69 Ae. aegypti pools, comprised of a total of 1,738 F1 adults, yielded ZIKV upon culture, giving a minimum filial infection rate of 1:290. In contrast, none of 803 F1 Ae. albopictus adults (32 pools) yielded ZIKV. The MFIR for Ae. aegypti was comparable to MFIRs reported for other flaviviruses in mosquitoes, including dengue, Japanese encephalitis, yellow fever, West Nile, and St. Louis encephalitis viruses. The results suggest that vertical transmission may provide a potential mechanism for the virus to survive during adverse conditions.

Conformational Heterogeneity of Intracellular Loop 3 of the μ-opioid G-protein Coupled Receptor

The Journal of Physical Chemistry. B. Nov, 2016  |  Pubmed ID: 27801588

G-protein coupled receptors (GPCRs), including the μ-opioid receptor, interact with G-proteins and other proteins via their intracellular face as required for signal transduction. However, characterization of the structure of the intracellular face of GPCRs is complicated by the experimental methods used for structural characterization. In the present study we undertook a series of long-time molecular dynamics (MD) simulations, ranging from 1 to 5 μs, on the μ-opioid receptor in both the dimeric and monomeric states. Results show intracellular loop 2 (ICL2) to sample an equilibrium between coiled and helical states. Intracellular loop 3 (ICL3) samples a wider range of conformations. Previously unobserved β-sheet structures were primarily sampled in the simulations initiated from the inactive dimer conformation. In contrast, helical structures were sampled in simulations initiated from the active, monomer conformation. Notably, in the dimeric form of the receptor, both intramolecular and intermolecular β-sheet structures were sampled, with the latter occurring between the two monomers. These results indicate that the sampling of β-sheet structures can maintain the ICL3 in an inactive conformation that contributes to stabilization of the dimeric form of the receptor via interchain β-sheet structures.

Advance in MicroRNA As a Potential Biomarker for Early Detection of Pancreatic Cancer

Biomarker Research. 2016  |  Pubmed ID: 27795830

Pancreatic cancer is characterized as a disease with low survival and high mortality because of no effective diagnostic and therapeutic strategies available in clinic. Conventional clinical diagnostic methods including serum markers and radiological imaging (CT, MRI, EUS, etc.) often fail to detect precancerous or early stage lesions. Development of effective biomarkers is unmet for reduction of mortality of pancreatic cancer. MicroRNAs (miRNAs) are a group of small non-protein-coding RNAs playing roles in regulation of cell physiology including tumorigenesis, apoptotic escape, proliferation, invasion, epithelial-mesenchymal transition (EMT), metastasis and chemoresistance. Various altered signaling pathways involving in molecular pathogenesis of pancreatic cancer are mediated by miRNAs as a role of either oncogenes or tumor suppressors. Among biomarkers developed including protein, metabolites, DNA, RNA, epigenetic mutation, miRNAs are superior because of its unique chemical property. Recent study suggests that miRNAs may be promising biomarkers used for early detection of pancreatic cancer. This review will update the progression made in early detection of pancreatic cancer.

Magnetic Nanoparticle Facilitated Drug Delivery for Cancer Therapy with Targeted and Image-Guided Approaches

Advanced Functional Materials. Jun, 2016  |  Pubmed ID: 27790080

With rapid advances in nanomedicine, magnetic nanoparticles (MNPs) have emerged as a promising theranostic tool in biomedical applications, including diagnostic imaging, drug delivery and novel therapeutics. Significant preclinical and clinical research has explored their functionalization, targeted delivery, controllable drug release and image-guided capabilities. To further develop MNPs for theranostic applications and clinical translation in the future, we attempt to provide an overview of the recent advances in the development and application of MNPs for drug delivery, specifically focusing on the topics concerning the importance of biomarker targeting for personalized therapy and the unique magnetic and contrast-enhancing properties of theranostic MNPs that enable image-guided delivery. The common strategies and considerations to produce theranostic MNPs and incorporate payload drugs into MNP carriers are described. The notable examples are presented to demonstrate the advantages of MNPs in specific targeting and delivering under image guidance. Furthermore, current understanding of delivery mechanisms and challenges to achieve efficient therapeutic efficacy or diagnostic capability using MNP-based nanomedicine are discussed.

Robust Dynamic Myocardial Perfusion CT Deconvolution for Accurate Residue Function Estimation Via Adaptive-weighted Tensor Total Variation Regularization: a Preclinical Study

Physics in Medicine and Biology. Nov, 2016  |  Pubmed ID: 27782004

Dynamic myocardial perfusion computed tomography (MPCT) is a promising technique for quick diagnosis and risk stratification of coronary artery disease. However, one major drawback of dynamic MPCT imaging is the heavy radiation dose to patients due to its dynamic image acquisition protocol. In this work, to address this issue, we present a robust dynamic MPCT deconvolution algorithm via adaptive-weighted tensor total variation (AwTTV) regularization for accurate residue function estimation with low-mA s data acquisitions. For simplicity, the presented method is termed 'MPD-AwTTV'. More specifically, the gains of the AwTTV regularization over the original tensor total variation regularization are from the anisotropic edge property of the sequential MPCT images. To minimize the associative objective function we propose an efficient iterative optimization strategy with fast convergence rate in the framework of an iterative shrinkage/thresholding algorithm. We validate and evaluate the presented algorithm using both digital XCAT phantom and preclinical porcine data. The preliminary experimental results have demonstrated that the presented MPD-AwTTV deconvolution algorithm can achieve remarkable gains in noise-induced artifact suppression, edge detail preservation, and accurate flow-scaled residue function and MPHM estimation as compared with the other existing deconvolution algorithms in digital phantom studies, and similar gains can be obtained in the porcine data experiment.

Tetraspanin-8 Promotes Hepatocellular Carcinoma Metastasis by Increasing ADAM12m Expression

Oncotarget. Jun, 2016  |  Pubmed ID: 27270327

Recent evidence indicates that tetraspanin-8 (TSPAN8) promotes tumor progression and metastasis. In this study, we explored the effects of TSPAN8 and the molecular mechanisms underlying hepatocellular carcinoma (HCC) metastasis using various HCC cell lines, tissues from 149 HCC patients, and animal models of HCC progression. We showed that elevated expression of TSPAN8 promoted HCC invasion in vitro and metastasis in vivo, but did not influence HCC cell proliferation in vitro. Increased TSPAN8 expression in human HCC was predictive of poor survival, and multivariate analyses indicated TSPAN8 expression to be an independent predictor for both postoperative overall survival and relapse-free survival. Importantly, TSPAN8 enhanced HCC invasion and metastasis by increasing ADAM12m expression. We therefore conclude that TSPAN8 and ADAM12m may be useful therapeutic targets for the prevention of HCC progression and metastasis.

Towards Development of Small Molecule Lipid II Inhibitors As Novel Antibiotics

PloS One. 2016  |  Pubmed ID: 27776124

Recently we described a novel di-benzene-pyrylium-indolene (BAS00127538) inhibitor of Lipid II. BAS00127538 (1-Methyl-2,4-diphenyl-6-((1E,3E)-3-(1,3,3-trimethylindolin-2-ylidene)prop-1-en-1-yl)pyryl-1-ium) tetrafluoroborate is the first small molecule Lipid II inhibitor and is structurally distinct from natural agents that bind Lipid II, such as vancomycin. Here, we describe the synthesis and biological evaluation of 50 new analogs of BAS00127538 designed to explore the structure-activity relationships of the scaffold. The results of this study indicate an activity map of the scaffold, identifying regions that are critical to cytotoxicity, Lipid II binding and range of anti-bacterial action. One compound, 6jc48-1, showed significantly enhanced drug-like properties compared to BAS00127538. 6jc48-1 has reduced cytotoxicity, while retaining specific Lipid II binding and activity against Enterococcus spp. in vitro and in vivo. Further, this compound showed a markedly improved pharmacokinetic profile with a half-life of over 13 hours upon intravenous and oral administration and was stable in plasma. These results suggest that scaffolds like that of 6jc48-1 can be developed into small molecule antibiotic drugs that target Lipid II.

Direct Regulation of Alternative Splicing by SMAD3 Through PCBP1 Is Essential to the Tumor-Promoting Role of TGF-β

Molecular Cell. Nov, 2016  |  Pubmed ID: 27746021

In advanced stages of cancers, TGF-β promotes tumor progression in conjunction with inputs from receptor tyrosine kinase pathways. However, mechanisms that underpin the signaling cooperation and convert TGF-β from a potent growth inhibitor to a tumor promoter are not fully understood. We report here that TGF-β directly regulates alternative splicing of cancer stem cell marker CD44 through a phosphorylated T179 of SMAD3-mediated interaction with RNA-binding protein PCBP1. We show that TGF-β and EGF respectively induce SMAD3 and PCBP1 to colocalize in SC35-positive nuclear speckles, and the two proteins interact in the variable exon region of CD44 pre-mRNA to inhibit spliceosome assembly in favor of expressing the mesenchymal isoform CD44s over the epithelial isoform CD44E. We further show that the SMAD3-mediated alternative splicing is essential to the tumor-promoting role of TGF-β and has a global influence on protein products of genes instrumental to epithelial-to-mesenchymal transition and metastasis.

Drug Discovery Via Human-Derived Stem Cell Organoids

Frontiers in Pharmacology. 2016  |  Pubmed ID: 27713700

Patient-derived cell lines and animal models have proven invaluable for the understanding of human intestinal diseases and for drug development although both inherently comprise disadvantages and caveats. Many genetically determined intestinal diseases occur in specific tissue microenvironments that are not adequately modeled by monolayer cell culture. Likewise, animal models incompletely recapitulate the complex pathologies of intestinal diseases of humans and fall short in predicting the effects of candidate drugs. Patient-derived stem cell organoids are new and effective models for the development of novel targeted therapies. With the use of intestinal organoids from patients with inherited diseases, the potency and toxicity of drug candidates can be evaluated better. Moreover, owing to the novel clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 genome-editing technologies, researchers can use organoids to precisely modulate human genetic status and identify pathogenesis-related genes of intestinal diseases. Therefore, here we discuss how patient-derived organoids should be grown and how advanced genome-editing tools may be applied to research on modeling of cancer and infectious diseases. We also highlight practical applications of organoids ranging from basic studies to drug screening and precision medicine.

Flavonoid Intake from Vegetables and Fruits is Inversely Associated with Colorectal Cancer Risk: a Case-control Study in China

The British Journal of Nutrition. Oct, 2016  |  Pubmed ID: 27650133

Flavonoids may play an important role in the protective effects of vegetables, fruits and tea against colorectal cancer. However, associations between flavonoids and colorectal cancer risk are inconsistent, and a few studies have evaluated the effect of flavonoids from different dietary sources separately. This study aimed to evaluate associations of flavonoids intake from different dietary sources with colorectal cancer risk in a Chinese population. From July 2010 to December 2015, 1632 eligible colorectal cancer cases and 1632 frequency-matched controls (age and sex) completed in-person interviews. A validated FFQ was used to estimate dietary flavonoids intake. Multivariate logistical regression models were used to calculate the OR and 95 % CI of colorectal cancer risk after adjusting for various confounders. No significant association was found between total flavonoids and colorectal cancer risk, with an adjusted OR of 1·06 (95 % CI 0·85, 1·32) comparing the highest with the lowest quartile. Anthocyanidins, flavanones and flavones intakes from total diet were found to be inversely associated with colorectal cancer risk. Compared with the lowest quartile, the adjusted OR for the highest quartile were 0·80 (95 % CI 0·64, 1·00) for anthocyanidins, 0·28 (95 % CI 0·22, 0·36) for flavanones and 0·54 (95 % CI 0·43, 0·67) for flavones. All subclasses of flavonoids from vegetables and fruits were inversely associated with colorectal cancer. However, no significant association was found between tea flavonoids and colorectal cancer risk. These data indicate that specific flavonoids, specifically flavonoids from vegetables and fruits, may be linked with the reduced risk of colorectal cancer.

MicroRNA-1275 Suppresses Cell Growth, and Retards G1/S Transition in Human Nasopharyngeal Carcinoma by Down-regulation of HOXB5

Journal of Cell Communication and Signaling. Sep, 2016  |  Pubmed ID: 27644407

Through analysis of a reported microarray-based high-throughput examination, we found that miR-1275 was significantly down-regulated in nasopharyngeal carcinoma (NPC). While its role and mechanism participated in NPC progression are still little known. Here, we explored the effect of miR-1275 on the progression of NPC. Results demonstrated that miR-1275 was markedly down-regulated in NPC tissues and cell lines. MiR-1275 markedly repressed cell growth as confirmed by CCK8 and colony formation assay, via inhibition of HOXB5 in NPC cell lines. Moreover, miR-1275 suppressed G1/S transition via inhibition of HOXB5. Further, oncogene HOXB5 was evidenced to be a potential target of miR-1275, and its expression was conversely correlated with miR-1275 expression in NPC. Collectively, our study indicated that miR-1275, a tumor suppressor, played a critical effect on NPC progression via inhibition of cell growth, and suppression of G1/S transition by targeting oncogenic HOXB5.

Production of Germline Transgenic Pigs Co-expressing Double Fluorescent Proteins by Lentiviral Vector

Animal Reproduction Science. Nov, 2016  |  Pubmed ID: 27639503

Genomic integration of transgene by lentiviral vector has been proved an efficient method to produce single-transgenic animals. But it failed to create multi-gene transgenic offspring. Here, we have exploited lentivirus to generate the double-transgenic piglets through the female germline. The recombinant lentivirus containing fluorescent proteins genes (DsRed1 and Venus) were injected into the perivitelline space of 2-cell stage in vitro porcine embryos. Compared to control group, there was no significantly decreased in the proportion of blastocysts, and the two fluorescent protein genes were co-expressed in almost all the injected embryos. Total of 32 injected in vitro embryos were transferred to 2 recipients. One recipient gave birth of three live offspring, and one female piglet was identified as genomic transgene integration by PCR analysis. Subsequently, the female transgenic founder was mated naturally with a wild-type boar and gave birth of two litters of total 23 F(1) generation piglets, among which Venus and DsRed1 genes were detected in 11 piglets and 10 kinds of organs by PCR and RT-PCR respectively. The co-expression of two fluorescent proteins was visible in four different frozen tissue sections from the RT-PCR positive piglets, and 3 to 5 copies of the transgenes were detected to be integrated into the second generation genome by southern blotting analysis. The transgenes were heritable and stably integrated in the F(1) generation. The results indicated for the first time that lentiviral vector combined with natural mating has the potential to become a simple and practical technology to create germline double-transgenic livestock or biomedical animals.

Meta-analysis of Associations Between DLG5 R30Q and P1371Q Polymorphisms and Susceptibility to Inflammatory Bowel Disease

Scientific Reports. Sep, 2016  |  Pubmed ID: 27633114

Growing evidence from recent studies has demonstrated an association between inflammatory bowel disease (IBD) susceptibility and two polymorphisms of DLG5 R30Q (rs1248696) and P1371Q (rs2289310), but the results remain controversial. We conducted a meta-analysis including a total of 22 studies with 10,878 IBD patients and 7917 healthy controls for R30Q and 5277 IBD cases and 4367 controls for P1371Q in order to systematically assess their association with the disease. The results indicated that R30Q was significantly associated with reduced susceptibility to IBD in Europeans by allelic and dominant comparisons, but not in overall population. No significant association was found between R30Q and Crohn's disease (CD) or ulcerative colitis (UC). P1371Q was associated with increased risk of IBD in Europeans and Americans. On the contrary, a decreased risk of IBD was observed in Asian population for P1371Q. In disease subgroup analysis, we found that P1371Q was also significantly associated with CD, but this relationship was not present for UC. In conclusion, our results strongly suggest that the both polymorphisms of DLG5 are correlated with IBD susceptibility in an ethnic-specific manner. Additional well-designed studies with large and diverse cohorts are needed to further strengthen our findings.

Robust Low-dose Dynamic Cerebral Perfusion CT Image Restoration Via Coupled Dictionary Learning Scheme

Journal of X-ray Science and Technology. Nov, 2016  |  Pubmed ID: 27612048

Dynamic cerebral perfusion x-ray computed tomography (PCT) imaging has been advocated to quantitatively and qualitatively assess hemodynamic parameters in the diagnosis of acute stroke or chronic cerebrovascular diseases. However, the associated radiation dose is a significant concern to patients due to its dynamic scan protocol. To address this issue, in this paper we propose an image restoration method by utilizing coupled dictionary learning (CDL) scheme to yield clinically acceptable PCT images with low-dose data acquisition. Specifically, in the present CDL scheme, the 2D background information from the average of the baseline time frames of low-dose unenhanced CT images and the 3D enhancement information from normal-dose sequential cerebral PCT images are exploited to train the dictionary atoms respectively. After getting the two trained dictionaries, we couple them to represent the desired PCT images as spatio-temporal prior in objective function construction. Finally, the low-dose dynamic cerebral PCT images are restored by using a general DL image processing. To get a robust solution, the objective function is solved by using a modified dictionary learning based image restoration algorithm. The experimental results on clinical data show that the present method can yield more accurate kinetic enhanced details and diagnostic hemodynamic parameter maps than the state-of-the-art methods.

[Efficacy of Three Prognostic Scoring Systems on Evaluating the Prognosis for Patients with Chronic Myeloid Leukemia]

Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences. Aug, 2016  |  Pubmed ID: 27600007

To retrospectively analyze the efficacy of three prognostic scoring systems on evaluating the prognosis for patients with chronic myeloid leukemia (CML) in chronic phase (CP).

Calculating Distribution Coefficients Based on Multi-scale Free Energy Simulations: an Evaluation of MM and QM/MM Explicit Solvent Simulations of Water-cyclohexane Transfer in the SAMPL5 Challenge

Journal of Computer-aided Molecular Design. Nov, 2016  |  Pubmed ID: 27577746

One of the central aspects of biomolecular recognition is the hydrophobic effect, which is experimentally evaluated by measuring the distribution coefficients of compounds between polar and apolar phases. We use our predictions of the distribution coefficients between water and cyclohexane from the SAMPL5 challenge to estimate the hydrophobicity of different explicit solvent simulation techniques. Based on molecular dynamics trajectories with the CHARMM General Force Field, we compare pure molecular mechanics (MM) with quantum-mechanical (QM) calculations based on QM/MM schemes that treat the solvent at the MM level. We perform QM/MM with both density functional theory (BLYP) and semi-empirical methods (OM1, OM2, OM3, PM3). The calculations also serve to test the sensitivity of partition coefficients to solute polarizability as well as the interplay of the quantum-mechanical region with the fixed-charge molecular mechanics environment. Our results indicate that QM/MM with both BLYP and OM2 outperforms pure MM. However, this observation is limited to a subset of cases where convergence of the free energy can be achieved.

IASM: A System for the Intelligent Active Surveillance of Malaria

Computational and Mathematical Methods in Medicine. 2016  |  Pubmed ID: 27563343

Malaria, a life-threatening infectious disease, spreads rapidly via parasites. Malaria prevention is more effective and efficient than treatment. However, the existing surveillance systems used to prevent malaria are inadequate, especially in areas with limited or no access to medical resources. In this paper, in order to monitor the spreading of malaria, we develop an intelligent surveillance system based on our existing algorithms. First, a visualization function and active surveillance were implemented in order to predict and categorize areas at high risk of infection. Next, socioeconomic and climatological characteristics were applied to the proposed prediction model. Then, the redundancy of the socioeconomic attribute values was reduced using the stepwise regression method to improve the accuracy of the proposed prediction model. The experimental results indicated that the proposed IASM predicted malaria outbreaks more close to the real data and with fewer variables than other models. Furthermore, the proposed model effectively identified areas at high risk of infection.

Scalable Fabrication of Multiplexed Plasmonic Nanoparticle Structures Based on AFM Lithography

Small (Weinheim an Der Bergstrasse, Germany). Aug, 2016  |  Pubmed ID: 27553257

A controllable and scalable strategy is developed to fabricate multiplexed plasmonic nanoparticle structures by mechanical scratching with AFM lithography, which exhibit multiplex plasmonic properties and surface-enhanced Raman scattering responses. It offers an intuitive way to explore the plasmonic effects on performance of organic light-emitting diodes device integrating with multiplexed plasmonic nanostructures.

DCUN1D3 Activates SCFSKP2 Ubiquitin E3 Ligase Activity and Cell Cycle Progression Under UV Damage

Oncotarget. Sep, 2016  |  Pubmed ID: 27542266

Our previous study showed that knockdown the endogenous expression of DCUN1D3 (also called SCCRO3 or DCNL3) blocked the S phase progression after UV irradiation. Here, we show that the silence of DCUN1D3 can increase the cyclin-dependent kinase inhibitor p27 protein levels after UV irradiation. Through Co-immunoprecipitation experiments, we found that DCUN1D3 bound to CAND1. And DCUN1D3 knockdown synergized with CAND1 over-expression in arresting the S phase. Given the CAND1's established role in Cullin-1 neddylation, we found Cullin-1 was less neddylated in DCUN1D3 deficient cells. So the silence of DCUN1D3 can inhibit the formation of SCFSKP2 complex by reducing Cullin-1 neddylation. Given that p27 is the primary target of SCFSKP2 complex, the cells lost DCUN1D3 showed a remarkable accumulation of p27 to cause S phase block.

The Complete Genome Sequence of PE3-1, a Novel E. Coli O153 Phage

Archives of Virology. Nov, 2016  |  Pubmed ID: 27541819

A novel virulent phage PE3-1 against E. coli O153 was isolated from an aeration tank in a wastewater treatment plant. Transmission electron microscopy images showed that phage PE3-1 had an icosahedral head and a short tail, which revealed that it was a member of the family Podoviridae of the order Caudovirales. The complete PE3-1 genome consisted of 39,093 bp and was a linear double-stranded DNA with an average GC content of 49.93 %. Phage PE3-1 showed homology to the T7-like phages in 48 open reading frames (ORFs), but it differed from previously reported E .coli phages in morphology and bioinformatics analysis. This indicated that phage PE3-1 is a new member of the genus T7 virus.

Elevating CLIC4 in Multiple Cell Types Reveals a TGF- Dependent Induction of a Dominant Negative Smad7 Splice Variant

PloS One. 2016  |  Pubmed ID: 27536941

CLIC4 (Chloride intracellular channel 4) belongs to a family of putative intracellular chloride channel proteins expressed ubiquitously in multiple tissues. CLIC4 is predominantly soluble and traffics between the cytoplasm and nucleus and participates in cell cycle control and differentiation. Transforming growth factor beta (TGF-β) elevates CLIC4, which enhances TGF-β signaling through CLIC4 mediated stabilization of phospho-Smad2/3. CLIC4 is essential for TGF-β induced conversion of fibroblasts to myofibroblasts and expression of matrix proteins, signaling via the p38MAPK pathway. Therefore, regulation of TGF-β signaling is a major mechanism by which CLIC4 modifies normal growth and differentiation. We now report that elevated CLIC4 alters Smad7 function, a feedback inhibitor of the TGF-β pathway. Overexpression of CLIC4 in keratinocytes, mouse embryonic fibroblasts and other mouse and human cell types increases the expression of Smad7Δ, a novel truncated form of Smad7. The alternatively spliced Smad7Δ variant is missing 94bp in exon 4 of Smad 7 and is conserved between mouse and human cells. The deletion is predicted to lack the TGF-β signaling inhibitory MH2 domain of Smad7. Treatment with exogenous TGF-β1 also enhances expression of Smad7Δ that is amplified in the presence of CLIC4. While Smad7 expression inhibits TGF-β signaling, exogenously expressed Smad7Δ does not inhibit TGF-β signaling as determined by TGF-β dependent proliferation, reporter assays and phosphorylation of Smad proteins. Instead, exogenous Smad7Δ acts as a dominant negative inhibitor of Smad7, thus increasing TGF-β signaling. This discovery adds another dimension to the myriad ways by which CLIC4 modifies TGF-β signaling.

Human CD8+ T Cells Mediate Protective Immunity Induced by a Human Malaria Vaccine in Human Immune System Mice

Vaccine. Aug, 2016  |  Pubmed ID: 27502569

A number of studies have shown that CD8+ T cells mediate protective anti-malaria immunity in a mouse model. However, whether human CD8+ T cells play a role in protection against malaria remains unknown. We recently established human immune system (HIS) mice harboring functional human CD8+ T cells (HIS-CD8 mice) by transduction with HLA-A∗0201 and certain human cytokines using recombinant adeno-associated virus-based gene transfer technologies. These HIS-CD8 mice mount a potent, antigen-specific HLA-A∗0201-restricted human CD8+ T-cell response upon immunization with a recombinant adenovirus expressing a human malaria antigen, the Plasmodium falciparum circumsporozoite protein (PfCSP), termed AdPfCSP. In the present study, we challenged AdPfCSP-immunized HIS-CD8 mice with transgenic Plasmodium berghei sporozoites expressing full-length PfCSP and found that AdPfCSP-immunized (but not naïve) mice were protected against subsequent malaria challenge. The level of the HLA-A∗0201-restricted, PfCSP-specific human CD8+ T-cell response was closely correlated with the level of malaria protection. Furthermore, depletion of human CD8+ T cells from AdPfCSP-immunized HIS-CD8 mice almost completely abolished the anti-malaria immune response. Taken together, our data show that human CD8+ T cells mediate protective anti-malaria immunity in vivo.

Penalized Weighted Least-squares Approach for Multienergy Computed Tomography Image Reconstruction Via Structure Tensor Total Variation Regularization

Computerized Medical Imaging and Graphics : the Official Journal of the Computerized Medical Imaging Society. Oct, 2016  |  Pubmed ID: 27490315

Multienergy computed tomography (MECT) allows identifying and differentiating different materials through simultaneous capture of multiple sets of energy-selective data belonging to specific energy windows. However, because sufficient photon counts are not available in each energy window compared with that in the whole energy window, the MECT images reconstructed by the analytical approach often suffer from poor signal-to-noise and strong streak artifacts. To address the particular challenge, this work presents a penalized weighted least-squares (PWLS) scheme by incorporating the new concept of structure tensor total variation (STV) regularization, which is henceforth referred to as 'PWLS-STV' for simplicity. Specifically, the STV regularization is derived by penalizing higher-order derivatives of the desired MECT images. Thus it could provide more robust measures of image variation, which can eliminate the patchy artifacts often observed in total variation (TV) regularization. Subsequently, an alternating optimization algorithm was adopted to minimize the objective function. Extensive experiments with a digital XCAT phantom and meat specimen clearly demonstrate that the present PWLS-STV algorithm can achieve more gains than the existing TV-based algorithms and the conventional filtered backpeojection (FBP) algorithm in terms of both quantitative and visual quality evaluations.

Dietary Choline and Betaine Intake, Choline-metabolising Genetic Polymorphisms and Breast Cancer Risk: a Case-control Study in China

The British Journal of Nutrition. Sep, 2016  |  Pubmed ID: 27488260

Choline and betaine are essential nutrients involved in one-carbon metabolism and have been hypothesised to affect breast cancer risk. Functional polymorphisms in genes encoding choline-related one-carbon metabolism enzymes, including phosphatidylethanolamine N-methyltransferase (PEMT), choline dehydrogenase (CHDH) and betaine-homocysteine methyltransferase (BHMT), have important roles in choline metabolism and may thus interact with dietary choline and betaine intake to modify breast cancer risk. This study aimed to investigate the interactive effect of polymorphisms in PEMT, BHMT and CHDH genes with choline/betaine intake on breast cancer risk among Chinese women. This hospital-based case-control study consecutively recruited 570 cases with histologically confirmed breast cancer and 576 age-matched (5-year interval) controls. Choline and betaine intakes were assessed by a validated FFQ, and genotyping was conducted for PEMT rs7946, CHDH rs9001 and BHMT rs3733890. OR and 95 % CI were estimated using unconditional logistic regression. Compared with the highest quartile of choline intake, the lowest intake quartile showed a significant increased risk of breast cancer. The SNP PEMT rs7946, CHDH rs9001 and BHMT rs3733890 had no overall association with breast cancer, but a significant risk reduction was observed among postmenopausal women with AA genotype of BHMT rs3733890 (OR 0·49; 95 % CI 0·25, 0·98). Significant interactions were observed between choline intake and SNP PEMT rs7946 (P interaction=0·029) and BHMT rs3733890 (P interaction=0·006) in relation to breast cancer risk. Our results suggest that SNP PEMT rs7946 and BHMT rs3733890 may interact with choline intake on breast cancer risk.

Impact of XRCC1, GSTP1, and GSTM1 Polymorphisms on the Survival of Ovarian Carcinoma Patients Treated with Chemotherapy

Oncology Research and Treatment. 2016  |  Pubmed ID: 27487108

Single nucleotide polymorphic variants of DNA repair genes may improve drug efficacy through altering expression levels of the encoded proteins. This study evaluated the influence of genetic polymorphism GSTP1 Ile105Val, GSTM1 (null/non-null) and 2 XRCC1 polymorphisms (Arg194Trp and Arg399Gln) on the survival of ovarian carcinoma patients treated with chemotherapy.

Effect of Pyrolysis Temperature on the Chemical Oxidation Stability of Bamboo Biochar

Bioresource Technology. Oct, 2016  |  Pubmed ID: 27481469

Biochar produced by biomass pyrolysis has the advantage of carbon sequestration. However, some of the carbon atoms in biochar are not very stable. In this study, the effect of pyrolysis temperature on the chemical oxidation stability of bamboo biochar was investigated using the atomic ratios of H/C and O/C, Fourier transform infrared spectroscopy, and potassium dichromate (K2Cr2O7) oxidation spectrophotometric method. The results show that the carbon yield and ratios of H/C and O/C decreased from 71.72%, 0.71, and 0.32 to 38.48%, 0.22, and 0.06, respectively, as the temperature was increased from 300°C to 700°C. Moreover, the main oxygen-containing functional groups gradually decreased, while the degree of aromatization increased accordingly. The biochar showed a better stability at a higher pyrolysis temperature. The proportion of carbon loss, i.e., the amount of oxidized carbon with respect to the total carbon of the biochar, decreased from 16.52% to 6.69% with increasing temperature.

α-Ketoglutarate Accelerates the Initial Differentiation of Primed Human Pluripotent Stem Cells

Cell Metabolism. Sep, 2016  |  Pubmed ID: 27476976

Pluripotent stem cells (PSCs) can self-renew or differentiate from naive or more differentiated, primed, pluripotent states established by specific culture conditions. Increased intracellular α-ketoglutarate (αKG) was shown to favor self-renewal in naive mouse embryonic stem cells (mESCs). The effect of αKG or αKG/succinate levels on differentiation from primed human PSCs (hPSCs) or mouse epiblast stem cells (EpiSCs) remains unknown. We examined primed hPSCs and EpiSCs and show that increased αKG or αKG-to-succinate ratios accelerate, and elevated succinate levels delay, primed PSC differentiation. αKG has been shown to inhibit the mitochondrial ATP synthase and to regulate epigenome-modifying dioxygenase enzymes. Mitochondrial uncoupling did not impede αKG-accelerated primed PSC differentiation. Instead, αKG induced, and succinate impaired, global histone and DNA demethylation in primed PSCs. The data support αKG promotion of self-renewal or differentiation depending on the pluripotent state.

Physical Properties and Stabilization of Microcapsules Containing Thyme Oil by Complex Coacervation

Journal of Food Science. Sep, 2016  |  Pubmed ID: 27472246

The aim of this study was to produce and characterize microcapsules of thyme oil and finally appraise the extent of stability improvement. The optimum process conditions obtained from orthogonal tests were as follows: ratio of core material to wall 0.5, temperature 40 °C, pH value 3.0 and time 20 min, where the practical encapsulation efficiency was 85.17±1.35%. The microcapsules belong to the nanometric range as the average particle diameter was 531.17±77.12 nm. The results from structural analysis indicated that no significant chemical bond occurred during the encapsulation process and the microcapsules remained stable when the encapsulation was conducted at a temperature below 53.1 °C. Especially, the retention rate of thyme oil in microcapsules remained 39.21% at 4 °C, 36.99% at 25 °C and 33.80% at 40 °C after 30 d of storage. Moreover, protection from light exposure presented a positive impact on the storage stability of thyme oil microcapsules.

Functionalized Milk-protein-coated Magnetic Nanoparticles for MRI-monitored Targeted Therapy of Pancreatic Cancer

International Journal of Nanomedicine. 2016  |  Pubmed ID: 27462153

Engineered nanocarriers have emerged as a promising platform for cancer therapy. However, the therapeutic efficacy is limited by low drug loading efficiency, poor passive targeting to tumors, and severe systemic side effects. Herein, we report a new class of nanoconstructs based on milk protein (casein)-coated magnetic iron oxide (CNIO) nanoparticles for targeted and image-guided pancreatic cancer treatment. The tumor-targeting amino-terminal fragment (ATF) of urokinase plasminogen activator and the antitumor drug cisplatin (CDDP) were engineered on this nanoplatform. High drug loading (~25 wt%) and sustained release at physiological conditions were achieved through the exchange and encapsulation strategy. These ATF-CNIO-CDDP nanoparticles demonstrated actively targeted delivery of CDDP to orthotopic pancreatic tumors in mice. The effective accumulation and distribution of ATF-CNIO-CDDP was evidenced by magnetic resonance imaging, based on the T2-weighted contrast resulting from the specific accumulation of ATF-CNIO-CDDP in the tumor. Actively targeted delivery of ATF-CNIO-CDDP led to improved therapeutic efficacy in comparison with free CDDP and nontargeted CNIO-CDDP treatment. Meanwhile, less systemic side effects were observed in the nanocarrier-treated groups than that in the group treated with free CDDP. Hematoxylin and Eosin and Sirius Red staining of tumor sections revealed the possible disruption of stroma during the treatment with ATF-CNIO-CDDP. Overall, our results suggest that ATF-CNIO-CDDP can be an effective theranostic platform for active targeting-enhanced and image-guided cancer treatment while simultaneously reducing the systemic toxicity.

Low-dose Cerebral Perfusion Computed Tomography Image Restoration Via Low-rank and Total Variation Regularizations

Neurocomputing. Jul, 2016  |  Pubmed ID: 27440948

Cerebral perfusion x-ray computed tomography (PCT) is an important functional imaging modality for evaluating cerebrovascular diseases and has been widely used in clinics over the past decades. However, due to the protocol of PCT imaging with repeated dynamic sequential scans, the associative radiation dose unavoidably increases as compared with that used in conventional CT examinations. Minimizing the radiation exposure in PCT examination is a major task in the CT field. In this paper, considering the rich similarity redundancy information among enhanced sequential PCT images, we propose a low-dose PCT image restoration model by incorporating the low-rank and sparse matrix characteristic of sequential PCT images. Specifically, the sequential PCT images were first stacked into a matrix (i.e., low-rank matrix), and then a non-convex spectral norm/regularization and a spatio-temporal total variation norm/regularization were then built on the low-rank matrix to describe the low rank and sparsity of the sequential PCT images, respectively. Subsequently, an improved split Bregman method was adopted to minimize the associative objective function with a reasonable convergence rate. Both qualitative and quantitative studies were conducted using a digital phantom and clinical cerebral PCT datasets to evaluate the present method. Experimental results show that the presented method can achieve images with several noticeable advantages over the existing methods in terms of noise reduction and universal quality index. More importantly, the present method can produce more accurate kinetic enhanced details and diagnostic hemodynamic parameter maps.

Triptolide Inhibits Osteoclast Differentiation and Bone Resorption In Vitro Via Enhancing the Production of IL-10 and TGF-β1 by Regulatory T Cells

Mediators of Inflammation. 2016  |  Pubmed ID: 27413257

Triptolide, a purified component of Tripterygiumwilfordii Hook F, has been shown to have immunosuppressive and anti-inflammatory properties in rheumatoid arthritis (RA). Although triptolide has demonstrated that it could suppress bone destruction in collagen-induced mice, its therapeutic mechanism remains unclear. Many studies have investigated the effect of triptolide on Tregs and Tregs-related cytokine involved in RA. Additionally, previous studies have implied that Tregs inhibit osteoclast differentiation and bone resorption. Thus, in this study we aimed to explore the regulatory mechanism by which triptolide influences the Treg-mediated production of IL-10 and TGF-β1 to affect osteoclast differentiation and bone resorption. In cocultures system of Tregs and mouse bone marrow macrophages (BMMs), Tregs inhibited the differentiation of osteoclasts and reduced the resorbed areas significantly and the production of both IL-10 and TGF-β1 was upregulated. When the coculture systems were pretreated with triptolide, they produced higher levels of IL-10 and TGF-β1. Our data indicate that triptolide enhances the suppressive effects of Tregs on osteoclast differentiation and bone resorption by enhancing the secretion of IL-10 and TGF-β1. Tregs are most likely involved in the triptolide-mediated regulation of bone metabolism and may provide a potential therapeutic target for the treatment of inflammatory bone destruction.

Mucilaginibacter Pedocola Sp. Nov., Isolated from a Heavy-metal-contaminated Paddy Field

International Journal of Systematic and Evolutionary Microbiology. Oct, 2016  |  Pubmed ID: 27412244

Strain TBZ30T was isolated from soil of a heavy-metal-contaminated paddy field. Cells of strain TBZ30T were Gram-staining-negative, rod-shaped, non-motile and non-spore-forming. The isolate was strictly aerobic, pink-pigmented, catalase- and oxidase-positive and produced exopolysaccharides. On the basis of 16S rRNA gene phylogeny, strain TBZ30T belonged to the genus Mucilaginibacter and appeared most closely related to Mucilaginibacter gynuensis YC7003T (95.8 %), Mucilaginibacter litoreus BR-18T (95.4 %) and Mucilaginibacter mallensis MP1X4T (95.4 %). Strain TBZ30T contained menaquinone-7 as the only ubiquinone. The main cellular fatty acids included summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH), iso-C15 : 0, C16 : 0, iso-C17 : 0 3-OH and C16 : 1ω5c. The polar lipids were phosphatidylethanolamine, an unidentified phospholipid, two unidentified aminophospholipids, four unidentified aminolipids, three unidentified lipids and two unidentified glycolipids. The genomic DNA G+C content was 49.0 mol%. On the basis of polyphasic taxonomy analyses, strain TBZ30T represents a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter pedocola sp. nov. is proposed. The type strain is TBZ30T (=KCTC 42833T=CCTCC AB 2015301T).

Enhancement of Pork Jerky Using Co-cultures of Lactobacillus Bulgaricus and Angel Yeast

Indian Journal of Microbiology. Sep, 2016  |  Pubmed ID: 27407292

Strains of Lactobacillus bulgaricus and Angel Yeast were combined to ferment raw pork and make pork jerky. After fermentation, the jerky was dried and then tested for sensory evaluation, pH and free amino acid content. The results showed that the optimal conditions for fermentation using L. bulgaricus and Angel Yeast were: a pH of 6.5, a 1:1 (v/v) ratio of L. bulgaricus to Angel Yeast, a fermentation time of 42 h and temperature of 25 °C. The results showed that the pork jerky fermented with the combined strains was not very sour which was close to the pH of 7.0 and had a higher free amino acid content which was more than 68.3 mg/100 g compared with the pork jerky fermented by either L. bulgaricus or Angel Yeast alone. Overall, the results demonstrate that fermentation of raw pork with combined strains of L. bulgaricus and Angel Yeast improves the quality and flavor of pork jerky.

Disrupted Topological Organization of Structural and Functional Brain Connectomes in Clinically Isolated Syndrome and Multiple Sclerosis

Scientific Reports. Jul, 2016  |  Pubmed ID: 27403924

The brain connectome of multiple sclerosis (MS) has been investigated by several previous studies; however, it is still unknown how the network changes in clinically isolated syndrome (CIS), the earliest stage of MS, and how network alterations on a functional level relate to the structural level in MS disease. Here, we investigated the topological alterations of both the structural and functional connectomes in 41 CIS and 32 MS patients, compared to 35 healthy controls, by combining diffusion tensor imaging and resting-state functional MRI with graph analysis approaches. We found that the structural connectome showed a deviation from the optimal pattern as early as the CIS stage, while the functional connectome only showed local changes in MS patients, not in CIS. When comparing two patient groups, the changes appear more severe in MS. Importantly, the disruptions of structural and functional connectomes in patients occurred in the same direction and locally correlated in sensorimotor component. Finally, the extent of structural network changes was correlated with several clinical variables in MS patients. Together, the results suggested early disruption of the structural brain connectome in CIS patients and provided a new perspective for investigating the relationship of the structural and functional alterations in MS.

Detection of Organophosphorus Pesticides with Colorimetry and Computer Image Analysis

Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry. 2016  |  Pubmed ID: 27396650

Organophosphorus pesticides (OPs) represent a very important class of pesticides that are widely used in agriculture because of their relatively high-performance and moderate environmental persistence, hence the sensitive and specific detection of OPs is highly significant. Based on the inhibitory effect of acetylcholinesterase (AChE) induced by inhibitors, including OPs and carbamates, a colorimetric analysis was used for detection of OPs with computer image analysis of color density in CMYK (cyan, magenta, yellow and black) color space and non-linear modeling. The results showed that there was a gradually weakened trend of yellow intensity with the increase of the concentration of dichlorvos. The quantitative analysis of dichlorvos was achieved by Artificial Neural Network (ANN) modeling, and the results showed that the established model had a good predictive ability between training sets and predictive sets. Real cabbage samples containing dichlorvos were detected by colorimetry and gas chromatography (GC), respectively. The results showed that there was no significant difference between colorimetry and GC (P > 0.05). The experiments of accuracy, precision and repeatability revealed good performance for detection of OPs. AChE can also be inhibited by carbamates, and therefore this method has potential applications in real samples for OPs and carbamates because of high selectivity and sensitivity.

In Vivo MRI and X-Ray Bifunctional Imaging of Polymeric Composite Supplemented with GdPO4 ·H2 O Nanobundles for Tracing Bone Implant and Bone Regeneration

Advanced Healthcare Materials. Sep, 2016  |  Pubmed ID: 27385162

Homogeneous and monodisperse GdPO4 ·H2 O nanobundles are successfully synthesized via a solvothermal method. Then, GdPO4 ·H2 O are incorporated into the composite of hydroxyapatite and poly(lactic-co-glycolic acid) to obtain a biodegradable and traceable bone implant. After implanted, the GdPO4 ·H2 O/HA/PLGA implant and the newly formed bone can be easily traced and observed through the combination of magnetic resonance imaging and X-ray imaging.

Chlorogenic Acid Inhibits Cholestatic Liver Injury Induced by α-naphthylisothiocyanate: Involvement of STAT3 and NFκB Signalling Regulation

The Journal of Pharmacy and Pharmacology. Sep, 2016  |  Pubmed ID: 27367057

Chlorogenic acid (CGA) is one of the most widely consumed polyphenols in diets and is recognized to be a natural hepatoprotective agent. Here, we evaluated the protective effect and the potential mechanism of CGA against ɑ-naphthylisothiocyanate (ANIT)-induced cholestasis and liver injury.

Fabrication of Novel Vesicles of Triptolide for Antirheumatoid Activity with Reduced Toxicity in Vitro and in Vivo

International Journal of Nanomedicine. 2016  |  Pubmed ID: 27354796

Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (γ-PGA-l-PAE-TP [PPT]), in which TP was loaded by a poly-γ-glutamic acid-grafted l-phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98±15 nm, the polydispersity index is 0.18, the zeta potential is -35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice (P<0.01) and had no side effects or toxic effects on the thymus index (P>0.05) and spleen index (P>0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells (P>0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment.

Resistin Impairs Glucose Permeability in EA.hy926 Cells by Down-regulating GLUT1 Expression

Molecular and Cellular Endocrinology. Oct, 2016  |  Pubmed ID: 27353463

Type 2 diabetes mellitus (T2DM) is a chronic disease which is now affecting the health of more and more people in the world. Resistin, discovered in 2001, is considered to be closely related to metabolic dysfunction and obesity. Previous study showed that hyperglycemia is always accompanied by a high serum resistin concentration. We therefore investigated whether resistin can mediate glucose transfer across the blood-tissue barrier. Here, we employed a transwell system to analyze glucose permeability in EA.hy926 human endothelial cells treated without or with human resistin. In EA.hy926 cells treated with resistin, the permeability to glucose was heavily impaired. This was due to the down-regulation of GLUT1 expression as a result of the treatment, rather than regulation of tight junctions. In addition, overexpression of GLUT1 in EA.hy926 cells was able to recover the blocking effect of resistin on glucose permeability. We further found that resistin could inhibit the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and consequently impede the transcription of GLUT1. The results of the present study suggested that resistin could cause glucose retention in serum and thus result in hyperglycemia. This provides a novel explanation for hyperglycemia and a potential new way of treating type 2 diabetes mellitus.

Clinical Significance of IgM and C3 Glomerular Deposition in Primary Focal Segmental Glomerulosclerosis

Clinical Journal of the American Society of Nephrology : CJASN. Sep, 2016  |  Pubmed ID: 27340287

Glomerular IgM deposition is commonly shown in primary FSGS and sometimes accompanied by C3 deposition. Clinical presentation and treatment outcomes of these patients are not investigated in detail.

Structural Insights of a Hormone Sensitive Lipase Homologue Est22

Scientific Reports. Jun, 2016  |  Pubmed ID: 27328716

Hormone sensitive lipase (HSL) catalyzes the hydrolysis of triacylglycerols into fatty acids and glycerol, thus playing key roles in energy homeostasis. However, the application of HSL serving as a pharmaceutical target and an industrial biocatalyst is largely hampered due to the lack of high-resolution structural information. Here we report biochemical properties and crystal structures of a novel HSL homologue esterase Est22 from a deep-sea metagenomic library. Est22 prefers short acyl chain esters and has a very high activity with substrate p-nitrophenyl butyrate. The crystal structures of wild type and mutated Est22 with its product p-nitrophenol are solved with resolutions ranging from 1.4 Å to 2.43 Å. The Est22 exhibits a α/β-hydrolase fold consisting with a catalytic domain and a substrate-recognizing cap domain. Residues Ser188, Asp287, and His317 comprise the catalytic triad in the catalytic domain. The p-nitrophenol molecule occupies the substrate binding pocket and forms hydrogen bonds with adjacent residues Gly108, Gly109, and Gly189. Est22 exhibits a dimeric form in solution, whereas mutants D287A and H317A change to polymeric form, which totally abolished its enzymatic activities. Our study provides insights into the catalytic mechanism of HSL family esterase and facilitates the understanding for further industrial and biotechnological applications of esterases.

Phenotypic Evaluation and Genetic Dissection of Resistance to Phytophthora Sojae in the Chinese Soybean Mini Core Collection

BMC Genetics. Jun, 2016  |  Pubmed ID: 27316671

Phytophthora root and stem rot (PRR) caused by Phytophthora sojae is one of the most serious diseases affecting soybean (Glycine max (L.) Merr.) production all over the world. The most economical and environmentally-friendly way to control the disease is the exploration and utilization of resistant varieties.

Optimisation for Assay of Fluorescein Diacetate Hydrolytic Activity As a Sensitive Tool to Evaluate Impacts of Pollutants and Nutrients on Microbial Activity in Coastal Sediments

Marine Pollution Bulletin. Sep, 2016  |  Pubmed ID: 27315754

Fluorescein diacetate (FDA) assay has been widely applied in coastal research to quantify microbial activity in sediments. However, the present FDA assay procedures embodied in sediment studies potentially include operational errors since the protocol was established for studies of terrestrial soil. In the present study, we optimised the procedure of FDA assay using sandy and cohesive sediments to improve experiential sensitivity and reproducibility. The optimised method describes quantitative measurement of the fluorescein produced when 1.0g of fresh sediment is incubated with 50mM phosphate buffer solution (pH: 7.3) and glass beads (2g) at 35°C for 1h under a rotation of 50rpm. The covariation coefficient of the optimised method ranged from 1.9% to 3.8% and the method sensitivity ranged from 0.25 to 1.57. The improved protocol provides a more reliable measurement of the FDA hydrolysis rate over a wide range of sediments compared to the original method.

Capsid-CPSF6 Interaction Is Dispensable for HIV-1 Replication in Primary Cells but Is Selected During Virus Passage In Vivo

Journal of Virology. Aug, 2016  |  Pubmed ID: 27307565

Cleavage and polyadenylation specificity factor subunit 6 (CPSF6), a host factor that interacts with the HIV-1 capsid (CA) protein, is implicated in diverse functions during the early part of the HIV-1 life cycle, including uncoating, nuclear entry, and integration targeting. Preservation of CA binding to CPSF6 in vivo suggests that this interaction is fine-tuned for efficient HIV-1 replication in physiologically relevant settings. Nevertheless, this possibility has not been formally examined. To assess the requirement for optimal CPSF6-CA binding during infection of primary cells and in vivo, we utilized a novel CA mutation, A77V, that significantly reduced CA binding to CPSF6. The A77V mutation rendered HIV-1 largely independent from TNPO3, NUP358, and NUP153 for infection and altered the integration site preference of HIV-1 without any discernible effects during the late steps of the virus life cycle. Surprisingly, the A77V mutant virus maintained the ability to replicate in monocyte-derived macrophages, primary CD4(+) T cells, and humanized mice at a level comparable to that for the wild-type (WT) virus. Nonetheless, revertant viruses that restored the WT CA sequence and hence CA binding to CPSF6 emerged in three out of four A77V-infected animals. These results suggest that the optimal interaction of CA with CPSF6, though not absolutely essential for HIV-1 replication in physiologically relevant settings, confers a significant fitness advantage to the virus and thus is strictly conserved among naturally circulating HIV-1 strains.

Double-hole Codoped Huge-gap Semiconductor ZrO2 for Visible-light Photocatalysis

Physical Chemistry Chemical Physics : PCCP. Jun, 2016  |  Pubmed ID: 27301769

Double-hole doping is an effective approach to engineer the band structures of semiconductors for enhancing the photoelectrochemical performance. Here, we explore the anionic monodoping (i.e. N, C, and P) and codoping (i.e. N + N, C + S, and N + P pairs) effects on the electronic structures and photocatalytic activities of ZrO2 by performing extensive density functional theory calculations. Upon anionic monodoping, several unoccupied impurity states appear within the band gap, which may trap the photogenerated carriers and then reduce the photocatalytic efficiency. Remarkably, double-hole doping via introducing three anionic (N + N), (C + S), and (N + P) codoping pairs in ZrO2 can not only effectively narrow the band gap, but can also create several fully filled delocalized intermediate bands for preventing the recombination of the photogenerated electron-hole pairs. Moreover, the band edge positions matching well with the redox potentials of water and the improved visible light absorption ability indicate that the three examined codoped ZrO2 systems are promising photocatalysts for visible light water splitting. In short, double-hole doping via anionic pairs provides an effective path to tune the huge-gap semiconductor band structures and to develop high efficient catalysts for solar-driven water splitting.

Structure of Penta-Alanine Investigated by Two-Dimensional Infrared Spectroscopy and Molecular Dynamics Simulation

The Journal of Physical Chemistry. B. Jun, 2016  |  Pubmed ID: 27299801

We have studied the structure of (Ala)5, a model unfolded peptide, using a combination of 2D IR spectroscopy and molecular dynamics (MD) simulation. Two different isotopomers, each bis-labeled with (13)C═O and (13)C═(18)O, were strategically designed to shift individual site frequencies and uncouple neighboring amide-I' modes. 2D IR spectra taken under the double-crossed ⟨π/4, -π/4, Y, Z⟩ polarization show that the labeled four-oscillator systems can be approximated by three two-oscillator systems. By utilizing the different polarization dependence of diagonal and cross peaks, we extracted the coupling constants and angles between three pairs of amide-I' transition dipoles through spectral fitting. These parameters were related to the peptide backbone dihedral angles through DFT calculated maps. The derived dihedral angles are all located in the polyproline-II (ppII) region of the Ramachandran plot. These results were compared to the conformations sampled by Hamiltonian replica-exchange MD simulations with three different CHARMM force fields. The C36 force field predicted that ppII is the dominant conformation, consistent with the experimental findings, whereas C22/CMAP predicted similar population for α+, β, and ppII, and the polarizable Drude-2013 predicted dominating β structure. Spectral simulation based on MD representative conformations and structure ensembles demonstrated the need to include multiple 2D spectral features, especially the cross-peak intensity ratio and shape, in structure determination. Using 2D reference spectra defined by the C36 structure ensemble, the best spectral simulation is achieved with nearly 100% ppII population, although the agreement with the experimental cross-peak intensity ratio is still insufficient. The dependence of population determination on the choice of reference structures/spectra and the current limitations on theoretical modeling relating peptide structures to spectral parameters are discussed. Compared with the previous results on alanine based oligopeptides, the dihedral angles of our fitted structure, and the most populated ppII structure from the C36 simulation are in good agreement with those suggesting a major ppII population. Our results provide further support for the importance of ppII conformation in the ensemble of unfolded peptides.

Application of TiO2-organobentonite Modified by Cetyltrimethylammonium Chloride Photocatalyst and Polyaluminum Chloride Coagulant for Pretreatment of Aging Landfill Leachate

Environmental Science and Pollution Research International. Sep, 2016  |  Pubmed ID: 27294701

This study investigated the treatment performance for aging leachate containing refractory organic pollutants by TiO2-organobentonite photocatalyst combined with polyaluminum chloride (PAC) coagulant. TiO2 was immobilized on organobentonite granules as a supporter modified by cetyltrimethylammonium chloride (CTAC). The prepared catalysts were characterized by ESEM, FTIR, and XRD analysis, which showed that TiO2-organobentonite catalyst had uniform coating of TiO2 on support. Chemical oxygen demand (COD) and NH3-N removal rates by combination of TiO2-CTAC2.0 photocatalysis and PAC coagulation were evaluated, optimized, and compared to that by either treatment alone, with respect to TiO2-CTAC2.0 dose, photocatalytic contact time, pH, and PAC dose. Furthermore, higher removal rates (COD 80 %; NH3-N 46 %) were achieved by response surface methodology (RSM) when TiO2-CTAC2.0 photocatalysis was followed by PAC coagulation at optimized conditions. The optimized experimental conditions were TiO2-CTAC2.0 dosage of 5.09 g/L, at pH 5.53, photocatalytic contact time for 180 min, and PAC dosage of 1062 mg/L.

Transcriptome Profiling Analysis of Rare Minnow (Gobiocypris Rarus) Gills After Waterborne Cadmium Exposure

Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics. Sep, 2016  |  Pubmed ID: 27292131

Rare minnow (Gobiocypris rarus) is a widely used experimental fish in risk assessments of aquatic pollutants in China. Cadmium (Cd) is one of the most toxic heavy metals in the world; however, few studies have used fish gills, a multi-functional organ. In this study, we characterized the differential expression of adult female rare minnow gills after sub-chronic waterborne Cd (75μg/L CdCl2) exposure for 35d. A total of 452 genes (209 up-regulated and 243 down-regulated) were identified by gene expression profiling using RNA-Seq before and after treatment. Of these differentially expressed genes, 75, 21, and 54 differentially expressed genes are related to ion transport, oxidation-reduction processes, and the immune response, respectively. The results of GO and KEGG enrichment analyses, together with the altered transcript levels of major histocompatibility complex (MHC) class I and class II molecules and the significant increases in the levels of serum tumor necrosis factor α (TNF-α), interleukin 1β (IL1β) and nuclear factor-κB (NF-κB), indicated a disruption of the immune system, particularly the induction of inflammation and autoimmunity. The significant down-regulation of coagulation factor XIII A1 polypeptide (F13A1), tripartite motif-containing protein 21 (TRIM21), and Golgi-associated plant pathogenesis-related protein (GAPr) during both acute (≤96h) and sub-chronic (35d) waterborne Cd exposure, as well as their dosage dependence, suggested that these three genes could be used as sensitive biomarkers for aquatic Cd risk assessment.

Obesity Indices for Prediction of Chronic Kidney Disease: 
a Cross-sectional Study in 26 655 Chinese Adults

Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences. May, 2016  |  Pubmed ID: 27269917

To investigate the associations between chronic kidney disease (CKD) and body mass index (BMI), waist circumference(WC), waist-to-height ratio (WheiR) in Chinese adults.

Single Molecule Analysis of Laser Localized Interstrand Crosslinks

Frontiers in Genetics. 2016  |  Pubmed ID: 27242893

DNA interstrand crosslinks (ICLs) block unwinding of the double helix, and have always been regarded as major challenges to replication and transcription. Compounds that form these lesions are very toxic and are frequently used in cancer chemotherapy. We have developed two strategies, both based on immunofluorescence (IF), for studying cellular responses to ICLs. The basis of each is psoralen, a photoactive (by long wave ultraviolet light, UVA) DNA crosslinking agent, to which we have linked an antigen tag. In the one approach, we have taken advantage of DNA fiber and immuno-quantum dot technologies for visualizing the encounter of replication forks with ICLs induced by exposure to UVA lamps. In the other, psoralen ICLs are introduced into nuclei in live cells in regions of interest defined by a UVA laser. The antigen tag can be displayed by conventional IF, as can the recruitment and accumulation of DNA damage response proteins to the laser localized ICLs. However, substantial difference between the technologies creates considerable uncertainty as to whether conclusions from one approach are applicable to those of the other. In this report, we have employed the fiber/quantum dot methodology to determine lesion density and spacing on individual DNA molecules carrying laser localized ICLs. We have performed the same measurements on DNA fibers with ICLs induced by exposure of psoralen to UVA lamps. Remarkably, we find little difference in the adduct distribution on fibers prepared from cells exposed to the different treatment protocols. Furthermore, there is considerable similarity in patterns of replication in the vicinity of the ICLs introduced by the two techniques.

Bioinspired Interface Engineering in Elastomer/Graphene Composites by Constructing Sacrificial Metal-Ligand Bonds

Macromolecular Rapid Communications. Jul, 2016  |  Pubmed ID: 27229634

It remains a huge challenge to create advanced elastomers combining high strength and great toughness. Despite enhanced strength and stiffness, elastomeric nanocomposites suffer notably reduced extensibility and toughness. Here, inspired by the concept of sacrificial bonding associated with many natural materials, a novel interface strategy is proposed to fabricate elastomer/graphene nanocomposites by constructing a strong yet sacrificial interface. This interface is composed of pyridine-Zn(2+) -catechol coordination motifs, which is strong enough to ensure uniform graphene dispersion and efficient stress transfer from matrix to fillers. Moreover, they are sacrificial under external stress, which dissipates much energy and facilitates chain orientation. As a result, the strength, modulus, and toughness of the elastomeric composites are simultaneously strikingly enhanced relative to elastomeric bulk. This work suggests a promising methodology of designing advanced elastomers with exceptional mechanical properties by engineering sacrificial bonds into the interface.

Patients With Combined Membranous Nephropathy and Focal Segmental Glomerulosclerosis Have Comparable Clinical and Autoantibody Profiles With Primary Membranous Nephropathy: A Retrospective Observational Study

Medicine. May, 2016  |  Pubmed ID: 27227951

Patients with combined membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS) have been reported with different clinical significance. Investigations on the possible mechanisms of the combined glomerular lesions are necessary but scarce. Twenty patients with both MN and FSGS lesions were enrolled in the study. Sixty-five patients with primary MN and 56 patients with primary FSGS were used as disease controls. Clinical data on renal biopsy and during follow-up were collected. Circulating anti-phospholipase A2 receptor (PLA2R) antibody, glomerular PLA2R expression, IgG4 deposition, and soluble urokinase receptor (suPAR) levels were detected. We found that patients with combined lesions presented with older age, less proteinuria, higher albumin, and better renal function on biopsy. These were comparable to the patients with primary MN, but differed from the patients with primary FSGS. Patients with combined lesions showed higher stages of MN, no cellular variant on FSGS classification, and more common (100.0%) tubulointerstitial injury than both primary MN and primary FSGS patients. In the patients with combined lesions, 80.0% had circulating anti-PLA2R antibody and 68.4% had IgG4 predominant deposition in glomeruli, which were comparable to primary MN. The patients with combined lesions had significantly lower urinary suPAR concentrations, than the primary FSGS patients (315.6 ± 151.0 vs 752.1 ± 633.9 pg/μmol; P = 0.002), but similar to the primary MN patients (267.9 ± 147.5 pg/μmol). We conclude that patients with combined MN and FSGS may share the same underlying pathogenesis with primary MN. The FSGS lesion might be secondary to primary MN.

Statins for the Prevention and Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome: A Systematic Review and Meta-analysis

Respirology (Carlton, Vic.). Aug, 2016  |  Pubmed ID: 27221951

The purpose of this meta-analysis was to assess whether statins could reduce the morbidity of acute lung injury and acute respiratory distress syndrome (ALI/ARDS) in high-risk patients and improve the clinical outcomes of patients with ALI/ARDS. Studies were obtained from PubMed, Medline, Embase and Cochrane Central Register of Controlled Trials. Randomized controlled trials (RCTs) and cohort studies, which reported morbidity, mortality, ventilator-free days, length of stay in intensive care unit and hospital or oxygenation index, were included in our meta-analysis. Risk ratio (RR) and weighted mean difference (WMD) were calculated using fixed or random effect model. A total of 13 studies covering 12 145 patients were included. Both the only RCT (P = 0.10) and cohort studies (RR, 1.02; 95% CI, 0.67 to 1.55; P = 0.94) showed that statin therapy did not lower the morbidity of ALI/ARDS in high-risk patients. The mortality of ALI/ARDS patients was less likely to be improved by statins (RCT, RR, 1.00; 95% CI, 0.84 to 1.20; P = 0.97; cohort studies, RR, 1.04; 95% CI, 0.85 to 1.27; P = 0.72). Moreover, no significant difference was observed in ventilator-free days, length of stay in intensive care unit as well as hospital and oxygenation index. This meta-analysis suggests that statins neither provide benefit for lowering the morbidity of ALI/ARDS in high-risk patients nor improve the clinical outcomes of ALI/ARDS patients. Hence, it may not be appropriate to advocate statin use for the prevention and treatment of ALI/ARDS.

Genomic Landscape Established by Allelic Imbalance in the Cancerization Field of a Normal Appearing Airway

Cancer Research. Jul, 2016  |  Pubmed ID: 27216194

Visually normal cells adjacent to, and extending from, tumors of the lung may carry molecular alterations characteristics of the tumor itself, an effect referred to as airway field of cancerization. This airway field has been postulated as a model for early events in lung cancer pathogenesis. Yet the genomic landscape of somatically acquired molecular alterations in airway epithelia of lung cancer patients has remained unknown. To begin to fill this void, we sought to comprehensively characterize the genomic architecture of chromosomal alterations inducing allelic imbalance (AI) in the airway field of the most common type of lung tumors, non-small cell lung cancer (NSCLC). To do so, we conducted a genome-wide survey of multiple spatially distributed normal-appearing airways, multiregion tumor specimens, and uninvolved normal tissues or blood from 45 patients with early-stage NSCLC. We detected alterations in airway epithelia from 22 patients, with an increased frequency in NSCLCs of squamous histology. Our data also indicated a spatial gradient of AI in samples at closer proximity to the NSCLC. Chromosome 9 displayed the highest levels of AI and comprised recurrent independent events. Furthermore, the airway field AI included oncogenic gains and tumor suppressor losses in known NSCLC drivers. Our results demonstrate that genome-wide AI is common in the airway field of cancerization, providing insights into early events in the pathogenesis of NSCLC that may comprise targets for early treatment and chemoprevention. Cancer Res; 76(13); 3676-83. ©2016 AACR.

Impact of a Bronchial Genomic Classifier on Clinical Decision Making in Patients Undergoing Diagnostic Evaluation for Lung Cancer

BMC Pulmonary Medicine. May, 2016  |  Pubmed ID: 27184093

Bronchoscopy is frequently used for the evaluation of suspicious pulmonary lesions found on computed tomography, but its sensitivity for detecting lung cancer is limited. Recently, a bronchial genomic classifier was validated to improve the sensitivity of bronchoscopy for lung cancer detection, demonstrating a high sensitivity and negative predictive value among patients at intermediate risk (10-60 %) for lung cancer with an inconclusive bronchoscopy. Our objective for this study was to determine if a negative genomic classifier result that down-classifies a patient from intermediate risk to low risk (<10 %) for lung cancer would reduce the rate that physicians recommend more invasive testing among patients with an inconclusive bronchoscopy.

Cerebral Perfusion Computed Tomography Deconvolution Via Structure Tensor Total Variation Regularization

Medical Physics. May, 2016  |  Pubmed ID: 27147322

Cerebral perfusion computed tomography (PCT) imaging as an accurate and fast acute ischemic stroke examination has been widely used in clinic. Meanwhile, a major drawback of PCT imaging is the high radiation dose due to its dynamic scan protocol. The purpose of this work is to develop a robust perfusion deconvolution approach via structure tensor total variation (STV) regularization (PD-STV) for estimating an accurate residue function in PCT imaging with the low-milliampere-seconds (low-mAs) data acquisition.

Laser Spectroscopy Applied to Environmental, Ecological, Food Safety, and Biomedical Research

Optics Express. Mar, 2016  |  Pubmed ID: 27136872

Laser spectroscopy provides many possibilities for multi-disciplinary applications in environmental monitoring, in the ecological field, for food safety investigations, and in biomedicine. The paper gives several examples of the power of multi-disciplinary applications of laser spectroscopy as pursued in our research group. The studies utilize mostly similar and widely applicable spectroscopic approaches. Air pollution and vegetation monitoring by lidar techniques, as well as agricultural pest insect monitoring and classification by elastic scattering and fluorescence spectroscopy are described. Biomedical aspects include food safety applications and medical diagnostics of sinusitis and otitis, with strong connection to the abatement of antibiotics resistance development.

Effects and Mechanism of Ball Milling on Torrefaction of Pine Sawdust

Bioresource Technology. Aug, 2016  |  Pubmed ID: 27136611

The effects and mechanism of ball milling on the torrefaction process were studied. Ball- and hammer-milled (screen size 1mm) pine sawdust samples were torrefied at three temperatures (230, 260, and 290°C) and two durations (30 and 60min) to investigate into their torrefaction behavior and physicochemical properties. The results showed that, under identical torrefaction conditions, torrefied ball-milled pine sawdust had a higher carbon content and fixed carbon, and lower hydrogen and oxygen contents than torrefied hammer-milled pine sawdust. Torrefied ball-milled pine sawdust produced lower mass and energy yields, but higher heating values than torrefied hammer-milled pine sawdust. Ball milling destroyed the crystalline structure of cellulose and thus reduced the thermal stability of hemicellulose, cellulose, and lignin, causing them to degrade at relatively lower temperatures. In conclusion, biomass pretreated with a combination of ball milling and torrefaction has the potential to produce an alternative fuel to coal.

Co-administration of α-GalCer Analog and TLR4 Agonist Induces Robust CD8(+) T-cell Responses to PyCS Protein and WT-1 Antigen and Activates Memory-like Effector NKT Cells

Clinical Immunology (Orlando, Fla.). 07, 2016  |  Pubmed ID: 27132023

In the present study, the combined adjuvant effect of 7DW8-5, a potent α-GalCer-analog, and monophosphoryl lipid A (MPLA), a TLR4 agonist, on the induction of vaccine-induced CD8(+) T-cell responses and protective immunity was evaluated. Mice were immunized with peptides corresponding to the CD8(+) T-cell epitopes of a malaria antigen, a circumsporozoite protein of Plasmodium yoelii, and a tumor antigen, a Wilms Tumor antigen-1 (WT-1), together with 7DW8-5 and MPLA, as an adjuvant. These immunization regimens were able to induce higher levels of CD8(+) T-cell responses and, ultimately, enhanced levels of protection against malaria and tumor challenges compared to the levels induced by immunization with peptides mixed with 7DW8-5 or MPLA alone. Co-administration of 7DW8-5 and MPLA induces activation of memory-like effector natural killer T (NKT) cells, i.e. CD44(+)CD62L(-)NKT cells. Our study indicates that 7DW8-5 greatly enhances important synergistic pathways associated to memory immune responses when co-administered with MPLA, thus rendering this combination of adjuvants a novel vaccine adjuvant formulation.

Imipramine Protects Retinal Ganglion Cells from Oxidative Stress Through the Tyrosine Kinase Receptor B Signaling Pathway

Neural Regeneration Research. Mar, 2016  |  Pubmed ID: 27127489

Retinal ganglion cell (RGC) degeneration is irreversible in glaucoma and tyrosine kinase receptor B (TrkB)-associated signaling pathways have been implicated in the process. In this study, we attempted to examine whether imipramine, a tricyclic antidepressant, may protect hydrogen peroxide (H2O2)-induced RGC degeneration through the activation of the TrkB pathway in RGC-5 cell lines. RGC-5 cell lines were pre-treated with imipramine 30 minutes before exposure to H2O2. Western blot assay showed that in H2O2 -damaged RGC-5 cells, imipramine activated TrkB pathways through extracellular signal-regulated protein kinase/TrkB phosphorylation. TUNEL staining assay also demonstrated that imipramine ameliorated H2O2 -induced apoptosis in RGC-5 cells. Finally, TrkB-IgG intervention was able to reverse the protective effect of imipramine on H2O2 -induced RGC-5 apoptosis. Imipramine therefore protects RGCs from oxidative stress-induced apoptosis through the TrkB signaling pathway.

Bayesian Dynamic Mediation Analysis

Psychological Methods. Apr, 2016  |  Pubmed ID: 27123750

Most existing methods for mediation analysis assume that mediation is a stationary, time-invariant process, which overlooks the inherently dynamic nature of many human psychological processes and behavioral activities. In this article, we consider mediation as a dynamic process that continuously changes over time. We propose Bayesian multilevel time-varying coefficient models to describe and estimate such dynamic mediation effects. By taking the nonparametric penalized spline approach, the proposed method is flexible and able to accommodate any shape of the relationship between time and mediation effects. Simulation studies show that the proposed method works well and faithfully reflects the true nature of the mediation process. By modeling mediation effect nonparametrically as a continuous function of time, our method provides a valuable tool to help researchers obtain a more complete understanding of the dynamic nature of the mediation process underlying psychological and behavioral phenomena. We also briefly discuss an alternative approach of using dynamic autoregressive mediation model to estimate the dynamic mediation effect. The computer code is provided to implement the proposed Bayesian dynamic mediation analysis. (PsycINFO Database Record

Efficacy and Safety of Spironolactone in Patients with Resistant Hypertension: A Meta-analysis of Randomised Controlled Trials

Heart, Lung & Circulation. Oct, 2016  |  Pubmed ID: 27118266

The treatment of resistant hypertension (RH) is challenging. Several observational studies have suggested that the addition of spironolactone to triple-drug therapy might have a promising anti-hypertensive effect on RH. To provide more definite evidence for the benefit of spironolactone, we performed a meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy and safety of spironolactone in RH patients.

Singly Bonded Monoadduct Rather Than Methanofullerene: Manipulating the Addition Pattern of Trimetallic Nitride Clusterfullerene Through One Endohedral Metal Atom Substitution

Chemistry (Weinheim an Der Bergstrasse, Germany). Jun, 2016  |  Pubmed ID: 27115985

Bingel-Hirsch reactions of trimetallic nitride clusterfullerenes (NCFs) generally yield methanofullerene (cyclopropane) adducts instead of singly bonded derivatives, which have been reported for monometallofullerenes. Herein, we report the synthesis and characterization of the Bingel-Hirsch derivative of a mixed metal nitride clusterfullerene (MMNCF) TiY2 N@Ih -C80 . Surprisingly, in contrast to the reported Bingel-Hirsch cyclopropane adducts of the analogous NCF Y3 N@Ih -C80 , the Bingel-Hirsch derivative of TiY2 N@Ih -C80 is the first singly bonded monoadduct (labeled as TiY2 N@C80 -Mono) to be reported, which was determined unambiguously by single-crystal X-ray crystallography. Besides, the reactivity of TiY2 N@Ih -C80 was found to be significantly improved relative to that of Y3 N@Ih -C80 . Upon substituting one endohedral yttrium (Y) atom of Y3 N@Ih -C80 with titanium (Ti), the Bingel-Hirsch derivative changes from the cyclopropane to the singly bonded monoadduct, revealing that not only the reactivity but also the addition pattern of NCFs can be manipulated simultaneously through one endohedral metal atom substitution.

Acute Effects on Pulmonary Function in Young Healthy Adults Exposed to Traffic-related Air Pollution in Semi-closed Transport Hub in Beijing

Environmental Health and Preventive Medicine. Sep, 2016  |  Pubmed ID: 27106573

Transport hub is an important part of urban comprehensive transportation system. Traffic-related air pollution can reach high level because of difficulty of diffusion and increase of emission in transport hub. However, whether exposure in this semi-closed traffic micro-environment causes acute changes in pulmonary function of commuters still needs to be explored.

Chemical Constituents and Sources of Ambient Particulate Air Pollution and Biomarkers of Endothelial Function in a Panel of Healthy Adults in Beijing, China

The Science of the Total Environment. Aug, 2016  |  Pubmed ID: 27101449

Exposure to ambient air pollution has been associated with endothelial dysfunction as reflected by short-term alterations in circulating biomarkers, but the chemical constituents and pollution sources behind the association has been unclear.

Long Non-Coding RNA-ROR Mediates the Reprogramming in Cardiac Hypertrophy

PloS One. 2016  |  Pubmed ID: 27082978

Cardiac hypertrophy associated with various cardiovascular diseases results in heart failure and sudden death. A clear understanding of the mechanisms of hypertrophy will benefit the development of novel therapies. Long non-coding RNAs (lncRNAs) have been shown to play essential roles in many biological process, however, whether lncRNA-ROR plays functional roles in the reprogramming of cardiomyocyte remains unclear.

Nedaplatin Sensitization of Cisplatin-resistant Human Non-small Cell Lung Cancer Cells

Oncology Letters. Apr, 2016  |  Pubmed ID: 27073518

Cisplatin (DDP) has been one of the most widely used chemotherapy drugs for advanced non-small cell lung cancer. However, the increase in the number of DDP-resistant cancer cells has become a major impediment in the clinical management of cancer. In the present study, for the first time, the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay was used to demonstrate that nedaplatin (NDP) could have a stronger inhibitory effect than DDP alone in DDP-resistant A549 (A549DDP) cells and that it could attenuate the resistance of these cells. Additionally, flow cytometry analysis showed that the apoptosis rate of these resistant cells when exposed to NDP was markedly increased and the number of cells in the G2 stage of the cell cycle was significantly increased. Furthermore, western blot analysis indicated that NDP decreased the protein expression of P-glycoprotein, tumor protein p53 and B-cell lymphoma 2, and increased the expression of Bcl-2-associated X protein, all of which could possibly improve the NDP intracellular drug concentration and promote cell apoptosis. These observations suggested that NDP could have higher efficacy in DDP-resistant lung cancer cells, and further studies applying more detailed analyses are warranted to elucidate the mechanism(s) behind this effect.

[The Same Disease with Different Syndromes: a Proteomic Study of Chronic Hepatitis B]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Mar, 2016  |  Pubmed ID: 27063173

To analyze the differential proteomic profiles of the plasma in patients with chronic hepatitis B presenting with damp-heat retention syndrome and liver stagnation-spleen deficiency syndrome.

Particle-Scale Modeling of Methane Emission During Pig Manure/Wheat Straw Aerobic Composting

Environmental Science & Technology. Apr, 2016  |  Pubmed ID: 27045933

Inefficient aerobic composting techniques significantly contribute to the atmospheric methane (CH4) levels. Macro-scale models assuming completely aerobic conditions cannot be used to analyze CH4 generation in strictly anaerobic environments. This study presents a particle-scale model for aerobic pig manure/wheat straw composting that incorporates CH4 generation and oxidation kinetics. Parameter estimation revealed that pig manure is characterized by high CH4 yield coefficient (0.6414 mol CH4 mol(-1) Cman) and maximum CH4 oxidation rate (0.0205 mol CH4 kg(-1) VS(aero) h(-1)). The model accurately predicted CH4 emissions (R(2) = 0.94, RMSE = 2888 ppmv, peak time deviation = 0 h), particularly in the self-heating and cooling phases. During mesophilic and thermophilic stages, a rapid increase of CH4 generation (0.0130 mol CH4 kg(-1) VS h(-1)) and methanotroph inactivation were simulated, implying that additional measures should be performed during these phases to mitigate CH4 emissions. Furthermore, CH4 oxidation efficiency was related to oxygen permeation through the composting particles. Reducing the ambient temperature and extending the aeration duration can decrease CH4 emission, but the threshold temperature is required to trigger the self-heating phase. These findings provide insights into CH4 emission during composting and may inform responsible strategies to counteract climate change.

Monte Carlo Dosimetric Parameter Study of a New (32)P Brachytherapy Source

The British Journal of Radiology. Jun, 2016  |  Pubmed ID: 27042802

Recently, a new catheter-based (32)P brachytherapy source has been developed (College of Chemistry, Sichuan University) for use in high-dose-rate afterloader. This study presents the results of the dosimetric data of the Geant4 Monte Carlo (MC) simulation toolkit for this new (32)P brachytherapy source.

Irinotecan Plus Fluorouracil-based Regimen As Second or Third-line Chemotherapy for Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

Thoracic Cancer. Mar, 2016  |  Pubmed ID: 27042229

No standard second-line regimen exists for the treatment of advanced esophageal squamous cell carcinoma (ESCC). The aim of this study was to evaluate the efficacy and safety of irinotecan and fluorouracil-based chemotherapy as a second or third-line regimen for advanced ESCC patients.

The Effect of Renal Denervation on Resistant Hypertension: Meta-analysis of Randomized Controlled Clinical Trials

Clinical and Experimental Hypertension (New York, N.Y. : 1993). 2016  |  Pubmed ID: 27018652

This meta-analysis was conducted to evaluate the efficiency of renal denervation (RDN) on resistant hypertension.

Predictive Value of EGFR Overexpression and Gene Amplification on Icotinib Efficacy in Patients with Advanced Esophageal Squamous Cell Carcinoma

Oncotarget. Apr, 2016  |  Pubmed ID: 27013591

This study aimed to search for a molecular marker for targeted epithelial growth factor receptor (EGFR) inhibitor Icotinib by analyzing protein expression and amplification of EGFR proto-oncogene in esophageal squamous cell carcinoma (ESCC) patients.Immunohistochemistry and fluorescence in situ hybridization (FISH) was used to assess EGFR expression and gene amplification status in 193 patients with ESCC. We also examined the association between EGFR overexpression and the efficacy of a novel EGFR TKI, icotinib, in 62 ESCC patients.Of the 193 patients, 95 (49.2%) patients showed EGFR overexpression (3+), and 47(24.4%) patients harbored EGFR FISH positivity. EGFR overexpression was significantly correlated with clinical stage and lymph node metastasis (p<0.05). In addition, EGFR overexpression was significantly correlated with EGFR FISH positivity (p<0.001). Among the 62 patients who received icotinib, the response rate was 17.6% for patients with high EGFR-expressing tumors, which was markedly higher than the rate (0%) for patients with low to moderate EGFR-expressing tumors (p=0.341). Furthermore, all cases responded to icotinib showed EGFR overexpression.In conclusion, our study suggests that EGFR overexpression might potentially be used in predicting the efficacy in patients treated with Icotinib. These data have implications for both clinical trial design and therapeutic strategies.

Different Influences of Lipofection and Electrotransfection on In Vitro Gene Delivery to Primary Cultured Cortex Neurons

Pain Physician. Mar, 2016  |  Pubmed ID: 27008293

Many pain states are linked to central nervous system (CNS) diseases involving the dysfunction of dendritic arborization, making restoration a promising therapeutic strategy. Transfection of primary cortex neurons offers the possibility to study mechanisms which are important for the restoration of proper arborization. Its progress is, however, limited at present due to the lack of suitable gene transfer techniques.

Angiogenesis in Tissue-engineered Nerves Evaluated Objectively Using MICROFIL Perfusion and Micro-CT Scanning

Neural Regeneration Research. Jan, 2016  |  Pubmed ID: 26981108

Angiogenesis is a key process in regenerative medicine generally, as well as in the specific field of nerve regeneration. However, no convenient and objective method for evaluating the angiogenesis of tissue-engineered nerves has been reported. In this study, tissue-engineered nerves were constructed in vitro using Schwann cells differentiated from rat skin-derived precursors as supporting cells and chitosan nerve conduits combined with silk fibroin fibers as scaffolds to bridge 10-mm sciatic nerve defects in rats. Four weeks after surgery, three-dimensional blood vessel reconstructions were made through MICROFIL perfusion and micro-CT scanning, and parameter analysis of the tissue-engineered nerves was performed. New blood vessels grew into the tissue-engineered nerves from three main directions: the proximal end, the distal end, and the middle. The parameter analysis of the three-dimensional blood vessel images yielded several parameters, including the number, diameter, connection, and spatial distribution of blood vessels. The new blood vessels were mainly capillaries and microvessels, with diameters ranging from 9 to 301 μm. The blood vessels with diameters from 27 to 155 μm accounted for 82.84% of the new vessels. The microvessels in the tissue-engineered nerves implanted in vivo were relatively well-identified using the MICROFIL perfusion and micro-CT scanning method, which allows the evaluation and comparison of differences and changes of angiogenesis in tissue-engineered nerves implanted in vivo.

Icotinib in Patients with Pretreated Advanced Esophageal Squamous Cell Carcinoma with EGFR Overexpression or EGFR Gene Amplification: A Single-Arm, Multicenter Phase 2 Study

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer. Jun, 2016  |  Pubmed ID: 26980473

Epidermal growth factor receptor (EGFR) has been reported to be overexpressed and amplified in a high percentage of patients with esophageal squamous cell carcinoma (ESCC). The activity of icotinib, an EGFR tyrosine kinase inhibitor, was assessed in previously treated ESCC with EGFR overexpression or amplification.

Respiratory Syncytial Virus (RSV) Pulmonary Infection in Humanized Mice Induces Human Anti-RSV Immune Responses and Pathology

Journal of Virology. May, 2016  |  Pubmed ID: 26962219

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease, which causes high rates of morbidity and mortality in infants and the elderly. Models of human RSV pulmonary disease are needed to better understand RSV pathogenesis and to assess the efficacy of RSV vaccines. We assessed the RSV-specific human innate, humoral, and cellular immune responses in humanized mice (mice with a human immune system [HIS mice]) with functional human CD4(+) T and B cells. These mice were generated by introduction of HLA class II genes, various human cytokines, and human B cell activation factor into immunodeficient NOD scid gamma (NSG) mice by the use of an adeno-associated virus vector, followed by engraftment of human hematopoietic stem cells. During the first 3 days of infection, HIS mice lost more weight and cleared RSV faster than NSG mice. Human chemokine (C-C motif) ligand 3 (CCL3) and human interleukin-1β (IL-1β) expression was detected in the RSV-infected HIS mice. The pathological features induced by RSV infection in HIS mice included peribronchiolar inflammation, neutrophil predominance in the bronchioalveolar lavage fluid, and enhanced airway mucus production. Human anti-RSV IgG and RSV-neutralizing antibodies were detected in serum and human anti-RSV mucosal IgA was detected in bronchioalveolar lavage fluid for up to 6 weeks. RSV infection induced an RSV-specific human gamma interferon response in HIS mouse splenocytes. These results indicate that human immune cells can induce features of RSV lung disease, including mucus hyperplasia, in murine lungs and that HIS mice can be used to elicit human anti-RSV humoral and cellular immunity.

Retrospective Analysis of Population-based Causes of Death and Life Expectancy in Urban Western China from 2003 to 2012

BMC Public Health. Mar, 2016  |  Pubmed ID: 26956019

Hitherto, a population-based analysis of the cause of death in urban areas of Western China has not been undertaken over an extended period. The aims of this study were to calculate the overall and annual cause-specific mortality rates by age and sex in urban areas of Western China from 2003 to 2012 and to evaluate the quality of the data.

A Fatal Case of "Bullous Erysipelas-like" Pseudomonas Vasculitis

Indian Journal of Dermatology. Jan-Feb, 2016  |  Pubmed ID: 26955132

Erysipelas is a generally benign superficial bacterial skin infection, and its bullous form constitutes a rare and more severe variant. We describe the first and fatal case of "bullous erysipelas-like" septic vasculitis due to Pseudomonas bacteremi. A 69-year-old Chinese man presenting with diarrhea and septic shock initially began to rapidly develop sharply defined erythematous plaques with non-hemorrhagic bullae over his lower limbs. Culture of the aspirate from the bullae was positive for Pseudomonas aeruginosa. This was also consistent with his blood cultures showing Pseudomonas bacteremia. Histology of the skin lesion showed microthrombi and neutrophilic infiltrates in blood vessels with Gram-negative bacilli extruding from the vessel walls, characteristic of septic vasculitis. The bullous erysipelas-like lesions seen in this patient represents a rare manifestation of both septic vasculitis and Pseudomonas infection.

Nicotine Induces Cardiomyocyte Hypertrophy Through TRPC3-Mediated Ca(2+)/NFAT Signalling Pathway

The Canadian Journal of Cardiology. Oct, 2016  |  Pubmed ID: 26952156

Nicotine is thought to be an important risk factor for the development of cardiovascular diseases. However, the effects of nicotine on cardiomyocyte hypertrophy are poorly understood. The present study was designed to explore the role of nicotine in cardiomyocyte hypertrophy and its underlying mechanism.

A Ratiometric Fluorescent Probe for Aluminum Ions Based-on Monomer/excimer Conversion and Its Applications to Real Samples

Talanta. May, 2016  |  Pubmed ID: 26946004

Excessive amount of aluminum is detrimental to growing plants or animals and people are likely to suffer from various diseases upon long-term exposure to aluminum ions. Therefore, sensitive and selective detection of trace amounts of Al(3+) in real samples is of great importance. Herein, a ratiometric fluorescent probe for detecting aluminum ions based on pyrene-1-butyric acid (Py-L-COOH) was developed, which function via monomer/excimer conversion. In the presence of Al(3+), the original monomer-state Py-L-COOH molecules coordinate with Al(3+) and form excimer, thus changing the emission wavelength from 350-400nm to 450-500nm and achieving the ratiometric detection for Al(3+). The probe responds to Al(3+) quickly and can be operable in aqueous media with a very low detection limit of 0.29µM. This system is capable of detecting Al(3+) in real samples and shows high selectivity. Furthermore, the probe exhibits low cytotoxicity and can be used in fluorescence imaging in Hela cell lines. The approach may provide an effective simple probe for aluminum ions determination with application to real samples, as well as offering insights for designing facile ratiometric fluorescent sensors.

A RUNX2-Mediated Epigenetic Regulation of the Survival of P53 Defective Cancer Cells

PLoS Genetics. Feb, 2016  |  Pubmed ID: 26925584

The inactivation of p53 creates a major challenge for inducing apoptosis in cancer cells. An attractive strategy is to identify and subsequently target the survival signals in p53 defective cancer cells. Here we uncover a RUNX2-mediated survival signal in p53 defective cancer cells. The inhibition of this signal induces apoptosis in cancer cells but not non-transformed cells. Using the CRISPR technology, we demonstrate that p53 loss enhances the apoptosis caused by RUNX2 knockdown. Mechanistically, RUNX2 provides the survival signal partially through inducing MYC transcription. Cancer cells have high levels of activating histone marks on the MYC locus and concomitant high MYC expression. RUNX2 knockdown decreases the levels of these histone modifications and the recruitment of the Menin/MLL1 (mixed lineage leukemia 1) complex to the MYC locus. Two inhibitors of the Menin/MLL1 complex induce apoptosis in p53 defective cancer cells. Together, we identify a RUNX2-mediated epigenetic mechanism of the survival of p53 defective cancer cells and provide a proof-of-principle that the inhibition of this epigenetic axis is a promising strategy to kill p53 defective cancer cells.

Analytical Performance of a Bronchial Genomic Classifier

BMC Cancer. Feb, 2016  |  Pubmed ID: 26920854

The current standard practice of lung lesion diagnosis often leads to inconclusive results, requiring additional diagnostic follow up procedures that are invasive and often unnecessary due to the high benign rate in such lesions (Chest 143:e78S-e92, 2013). The Percepta bronchial genomic classifier was developed and clinically validated to provide more accurate classification of lung nodules and lesions that are inconclusive by bronchoscopy, using bronchial brushing specimens (N Engl J Med 373:243-51, 2015, BMC Med Genomics 8:18, 2015). The analytical performance of the Percepta test is reported here.

Enhanced Photoresponse of Conductive Polymer Nanowires Embedded with Au Nanoparticles

Advanced Materials (Deerfield Beach, Fla.). Apr, 2016  |  Pubmed ID: 26901850

A conductive polymer nanowire embedded with a 1D Au nanoparticle chain with defined size, shape, and interparticle distance is fabricated which demonstrates enhanced photoresponse behavior. The precise and controllable positioning of 1D Au nanoparticle chain in the conductive polymer nanowire plays a critical role in modulating the photoresponse behavior by excitation light wavelength or power due to the coupled-plasmon effect of 1D Au nanoparticle chain.

Distinction Between Bacterial and Viral Infections by Serum Measurement of Human Neutrophil Lipocalin (HNL) and the Impact of Antibody Selection

Journal of Immunological Methods. May, 2016  |  Pubmed ID: 26899825

The distinction between acute infections of bacterial or viral causes is clinically important, but often very difficult even for experienced doctors. Previous studies indicated that serum measurements of HNL (Human Neutrophil Lipocalin) might be a superior diagnostic means in this regard, but also indicated that the antibody conformation of the HNL assay might have an impact on the diagnostic performance. The aim of the present report was to examine this further.

MEGSA: A Powerful and Flexible Framework for Analyzing Mutual Exclusivity of Tumor Mutations

American Journal of Human Genetics. Mar, 2016  |  Pubmed ID: 26899600

The central challenges in tumor sequencing studies is to identify driver genes and pathways, investigate their functional relationships, and nominate drug targets. The efficiency of these analyses, particularly for infrequently mutated genes, is compromised when subjects carry different combinations of driver mutations. Mutual exclusivity analysis helps address these challenges. To identify mutually exclusive gene sets (MEGS), we developed a powerful and flexible analytic framework based on a likelihood ratio test and a model selection procedure. Extensive simulations demonstrated that our method outperformed existing methods for both statistical power and the capability of identifying the exact MEGS, particularly for highly imbalanced MEGS. Our method can be used for de novo discovery, for pathway-guided searches, or for expanding established small MEGS. We applied our method to the whole-exome sequencing data for 13 cancer types from The Cancer Genome Atlas (TCGA). We identified multiple previously unreported non-pairwise MEGS in multiple cancer types. For acute myeloid leukemia, we identified a MEGS with five genes (FLT3, IDH2, NRAS, KIT, and TP53) and a MEGS (NPM1, TP53, and RUNX1) whose mutation status was strongly associated with survival (p = 6.7 × 10(-4)). For breast cancer, we identified a significant MEGS consisting of TP53 and four infrequently mutated genes (ARID1A, AKT1, MED23, and TBL1XR1), providing support for their role as cancer drivers.

Cutaneous T-cell Lymphoma (CTCL): Current Practices in Blood Assessment and the Utility of T-cell Receptor (TCR)-Vβ Chain Restriction

Journal of the American Academy of Dermatology. May, 2016  |  Pubmed ID: 26874819

Accurate quantification of malignant cells in the peripheral blood of patients with cutaneous T-cell lymphoma is important for early detection, prognosis, and monitoring disease burden.

Phase II and UGT1A1 Polymorphism Study of Two Different Irinotecan Dosages Combined with Cisplatin As First-Line Therapy for Advanced Gastric Cancer

Chemotherapy. 2016  |  Pubmed ID: 26872008

We investigated the efficacy and safety of biweekly irinotecan and cisplatin (IP) as first-line treatment in advanced gastric cancer patients.

Vitamin C Intake and Pancreatic Cancer Risk: A Meta-Analysis of Published Case-Control and Cohort Studies

PloS One. 2016  |  Pubmed ID: 26859881

Observational studies inconsistently reported the relationship between vitamin C intake and risk of pancreatic cancer. We conducted a meta-analysis of published case-control and cohort studies to quantify the association.

FANCM Interacts with PCNA to Promote Replication Traverse of DNA Interstrand Crosslinks

Nucleic Acids Research. Apr, 2016  |  Pubmed ID: 26825464

FANCM is a highly conserved DNA remodeling enzyme that promotes the activation of the Fanconi anemia DNA repair pathway and facilitates replication traverse of DNA interstrand crosslinks. However, how FANCM interacts with the replication machinery to promote traverse remains unclear. Here, we show that FANCM and its archaeal homolog Hef from Thermoplasma acidophilum interact with proliferating cell nuclear antigen (PCNA), an essential co-factor for DNA polymerases in both replication and repair. The interaction is mediated through a conserved PIP-box; and in human FANCM, it is strongly stimulated by replication stress. A FANCM variant carrying a mutation in the PIP-box is defective in promoting replication traverse of interstrand crosslinks and is also inefficient in promoting FANCD2 monoubiquitination, a key step of the Fanconi anemia pathway. Our data reveal a conserved interaction mode between FANCM and PCNA during replication stress, and suggest that this interaction is essential for FANCM to aid replication machines to traverse DNA interstrand crosslinks prior to post-replication repair.

The Diagnostic Application of RNA Sequencing in Patients with Thyroid Cancer: an Analysis of 851 Variants and 133 Fusions in 524 Genes

BMC Bioinformatics. Jan, 2016  |  Pubmed ID: 26818556

Thyroid carcinomas are known to harbor oncogenic driver mutations and advances in sequencing technology now allow the detection of these in fine needle aspiration biopsies (FNA). Recent work by The Cancer Genome Atlas (TCGA) Research Network has expanded the number of genetic alterations detected in papillary thyroid carcinomas (PTC). We sought to investigate the prevalence of these and other genetic alterations in diverse subtypes of thyroid nodules beyond PTC, including a variety of samples with benign histopathology. This is the first clinical evaluation of a large panel of TCGA-reported genomic alterations in thyroid FNAs.

An Empirical Polarizable Force Field Based on the Classical Drude Oscillator Model: Development History and Recent Applications

Chemical Reviews. 05, 2016  |  Pubmed ID: 26815602

Molecular mechanics force fields that explicitly account for induced polarization represent the next generation of physical models for molecular dynamics simulations. Several methods exist for modeling induced polarization, and here we review the classical Drude oscillator model, in which electronic degrees of freedom are modeled by charged particles attached to the nuclei of their core atoms by harmonic springs. We describe the latest developments in Drude force field parametrization and application, primarily in the last 15 years. Emphasis is placed on the Drude-2013 polarizable force field for proteins, DNA, lipids, and carbohydrates. We discuss its parametrization protocol, development history, and recent simulations of biologically interesting systems, highlighting specific studies in which induced polarization plays a critical role in reproducing experimental observables and understanding physical behavior. As the Drude oscillator model is computationally tractable and available in a wide range of simulation packages, it is anticipated that use of these more complex physical models will lead to new and important discoveries of the physical forces driving a range of chemical and biological phenomena.

Reduced PDCD4 Expression Promotes Cell Growth Through PI3K/Akt Signaling in Non-Small Cell Lung Cancer

Oncology Research. 2016  |  Pubmed ID: 26802652

It is largely recognized that PDCD4 is frequently lost in tumors of various origins, including lung cancer, and its loss contributes to tumor progression. However, its role and molecular mechanism remain largely unexplored in non-small cell lung cancer (NSCLC). In this study, downregulated PDCD4 mRNA expression was found in NSCLC tissues compared to their corresponding paracarcinoma tissues and distal paracarcinoma tissues. Induced expression of PDCD4 inhibited cell growth and proliferation and cell cycle transition in vitro. Conversely, knocking down PDCD4 expression promoted cell growth and proliferation. Mechanistically, PDCD4 inactivated PI3K/Akt signaling and its downstream cell cycle factors CCND1 and CDK4 to regulate cell growth in NSCLC. Additionally, PI3K-specific inhibitor Ly294002 suppressed the expression of pPI3K (Tyr458), pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Furthermore, Akt-specific inhibitor MK2206 inhibited the expression of pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Taken together, our study provides evidence that PDCD4 inhibits cell growth through PI3K/Akt signaling in NSCLC and may be a potential therapeutic target for NSCLC.

The Source of Mycobacterium Tuberculosis-specific IFN-γ Production in Peripheral Blood Mononuclear Cells of TB Patients

International Immunopharmacology. Mar, 2016  |  Pubmed ID: 26796515

Mycobacterium tuberculosis (Mtb)-specific IFN-γ secretion plays important roles in anti-tuberculosis (TB) immunity. Mtb-specific IFN-γ response can be induced in HIV/TB co-infected patients with a low CD4 lymphocyte count; this suggests that the source of Mtb-specific IFN-γ production is not limited in CD4(+) T lymphocytes. Currently, the major sources of Mtb-specific IFN-γ production and the function and phenotype of Mtb-specific IFN-γ-producing cells still remain unclear. Thirty-nine participants (24 active TB patients, 10 HIV/TB co-infected patients, and 5 healthy volunteers) were recruited according to conventional tests and Mtb-specific IFN-γ ELISPOT assay. Multicolor flow cytometry was used to investigate the production of intracellular IFN-γ in peripheral blood mononuclear cells (PBMCs) after Mtb-specific antigen stimulation. Our results showed that CD4(+), CD8(+) T cells and NK cells are all major sources of Mtb-specific IFN-γ production in PBMCs of TB patients. Moreover, CD8(+) T cells are the highest number of Mtb-specific IFN-γ-producing cells in HIV/TB co-infected patients. Although the activity of NK cells is significantly reduced in TB patients when compared with healthy controls, Mtb-specific antigen stimulation induces a significant increase in NK cell activity. We also showed that CD45RO is the characteristic marker of Mtb-specific IFN-γ-producing T cells but not that of Mtb-specific IFN-γ-producing NK cells in peripheral blood. High expression of CD11a may be the characteristic feature of Mtb-specific IFN-γ-producing NK cells. This study put forward a new insight on the source of antigen-specific IFN-γ-production in PBMCs of TB patients.

[Value and Safety of the Surgery with Vascular Resection and Reconstruction for Pancreatic Cancer]

Zhonghua Wai Ke Za Zhi [Chinese Journal of Surgery]. Jan, 2016  |  Pubmed ID: 26792355

To investigate the value and safety of the surgery with vascular resection and reconstruction during pancreatectomy for pancreatic cancer.

Application of Marrow Mesenchymal Stem Cell-derived Extracellular Matrix in Peripheral Nerve Tissue Engineering

Journal of Tissue Engineering and Regenerative Medicine. Jan, 2016  |  Pubmed ID: 26777754

To advance molecular and cellular therapy into the clinic for peripheral nerve injury, modification of neural scaffolds with the extracellular matrix (ECM) of peripheral nerves has been established as a promising alternative to direct inclusion of support cells and/or growth factors within a neural scaffold, while cell-derived ECM proves to be superior to tissue-derived ECM in the modification of neural scaffolds. Based on the fact that bone marrow mesenchymal stem cells (BMSCs), just like Schwann cells, are adopted as support cells within a neural scaffold, in this study we used BMSCs as parent cells to generate ECM for application in peripheral nerve tissue engineering. A chitosan nerve guidance conduit (NGC) and silk fibroin filamentous fillers were respectively prepared for co-culture with purified BMSCs, followed by decellularization to stimulate ECM deposition. The ECM-modified NGC and lumen fillers were then assembled into a chitosan-silk fibroin-based, BMSC-derived, ECM-modified neural scaffold, which was implanted into rats to bridge a 10 mm-long sciatic nerve gap. Histological and functional assessments after implantation showed that regenerative outcomes achieved by our engineered neural scaffold were better than those achieved by a plain chitosan-silk fibroin scaffold, and suggested the benefits of BMSC-derived ECM for peripheral nerve repair. Copyright © 2016 John Wiley & Sons, Ltd.

Cell Membrane Chromatography Coupled with UHPLC-ESI-MS/MS Method to Screen Target Components from Peucedanum Praeruptorum Dunn Acting on α1A Adrenergic Receptor

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. Feb, 2016  |  Pubmed ID: 26773893

Peucedanum praeruptorum Dunn (BaiHuaQianHu in Chinese) is a traditional Chinese medicine that has a long history of use in China. In this study, HEK 293 α1A adrenergic cell membrane chromatography was coupled with UHPLC-ESI-MS/MS and successfully used to identify active components from Peucedanum praeruptorum Dunn. Paeruptorin A, paeruptorin B, and paeruptorin C were identified with α1A adrenergic receptor activity. Pharmacological assays showed that tamsulosin hydrochloride, paeruptorin A, paeruptorin B, and paeruptorin C in concentrations of 1×10(-8) to 1×10(-4)mol/mL could relax prostate strips pre-contracted with adrenalin in a concentration dependent manner. Therefore, the HEK293 α1A cell membrane chromatography coupled UHPLC-ESI-MS/MS system may be a potentially useful drug discovery method for screening for medicinal herbal components with α1A adrenergic receptor inhibitory activity.

Efficacy and Safety of Fixed-Dose Perindopril Arginine/Amlodipine in Hypertensive Patients Not Adequately Controlled with Amlodipine 5 Mg or Perindopril Tert-Butylamine 4 Mg Monotherapy

Cardiology. 2016  |  Pubmed ID: 26771522

To assess the blood pressure-lowering efficacy and tolerability of perindopril/amlodipine fixed-dose combinations in Chinese patients with mild-to-moderate essential hypertension not adequately controlled with monotherapy alone.

Involvement of Hypoxia-inducible Factor-1α in the Oxidative Stress Induced by Advanced Glycation End Products in Murine Leydig Cells

Toxicology in Vitro : an International Journal Published in Association with BIBRA. Apr, 2016  |  Pubmed ID: 26743761

Hyperglycemia increases the formation of advanced glycation end products (AGEs), triggers oxidative impairments and influences inducible factor (HIF)-1α protein levels and transactivation function. Compromised HIF-1α in testis leads to male infertility. The aim of the study was to investigate the role of HIF-1α in oxidative stress induced by AGEs in murine Leydig TM3 cells. TM3 cells were treated with 50 μg/ml of AGEs, or HIF-1α siRNA or 500 μM of DMOG (dimethyloxalylglycine) respectively. The cells were also pretreated with HIF-1α siRNA or 500 μM of DMOG and then were treated with 50 μg/ml of AGEs. The formation of reactive oxygen species (ROS) and cell apoptosis was evaluated. The expression of caspase-3, Heme oxygenase (HO)-1, steroidogenic acute regulatory protein (StAR) and cytochrome P450 17α polypeptide 1 (CYP17A1) was examined by Western blotting. AGEs increased ROS production, induced apoptosis and activated HIF-1α and HO-1 in TM3 cells. HIF-1α attenuated the AGE-induced ROS formation and promoted apoptosis via the upregulation of caspase-3. Knockdown of HIF-1α inhibited the expression of CYP17A1 and StAR, and enhanced the inhibition of StAR and CYP17A1 by AGEs. These findings indicate that attenuated HIF-1α exacerbates the oxidative stress injury by AGEs in murine Leydig cells, and contributes to diabetic male infertility.

Improving the Photocurrent in Quantum-Dot-Sensitized Solar Cells by Employing Alloy PbxCd1-xS Quantum Dots As Photosensitizers

Nanomaterials (Basel, Switzerland). May, 2016  |  Pubmed ID: 28335226

Ternary alloy PbxCd1-xS quantum dots (QDs) were explored as photosensitizers for quantum-dot-sensitized solar cells (QDSCs). Alloy PbxCd1-xS QDs (Pb0.54Cd0.46S, Pb0.31Cd0.69S, and Pb0.24Cd0.76S) were found to substantially improve the photocurrent of the solar cells compared to the single CdS or PbS QDs. Moreover, it was found that the photocurrent increases and the photovoltage decreases when the ratio of Pb in PbxCd1-xS is increased. Without surface protecting layer deposition, the highest short-circuit current density reaches 20 mA/cm² under simulated AM 1.5 illumination (100 mW/cm²). After an additional CdS coating layer was deposited onto the PbxCd1-xS electrode, the photovoltaic performance further improved, with a photocurrent of 22.6 mA/cm² and an efficiency of 3.2%.

Whole Brain Functional Connectivity in Clinically Isolated Syndrome Without Conventional Brain MRI Lesions

European Radiology. Sep, 2016  |  Pubmed ID: 26714968

To investigate brain functional connectivity (FC) alterations in patients with clinically isolated syndromes (CIS) presenting without conventional brain MRI lesions, and to identify the FC differences between the CIS patients who converted to multiple sclerosis (MS) and those not converted during a 5-year follow-up.

Pyrene Derivative Emitting Red or Near-Infrared Light with Monomer/Excimer Conversion and Its Application to Ratiometric Detection of Hypochlorite

ACS Applied Materials & Interfaces. Jan, 2016  |  Pubmed ID: 26701212

Fluorescent sensors are attractive and versatile tools for both chemical sensing and biological imaging. Herein, a novel pyrene derivative fluorophore, Py-Cy, possessing the monomer/excimer conversion feature, was synthesized; and the design rationale for this fluorophore is combination of extending conjugation length and incorporating donor-π-acceptor structure. The positively charged Py-Cy shows quite good water solubility and exhibits absorption in the visible-light range, and its monomer and excimer emit red light and near-infrared light respectively, which is extremely beneficial for biosensing or bioimaging. To explore the potential utilization of this new fluorophore, we choose hypochlorite as a model analyte, which can break the double bond in the molecular structure, thereby generating the water-insoluble pyrenecarboxaldehyde; this process correspondingly leads to fluorescence changes and thus affords the ratiometric fluorescent detection of hypochlorite in real samples and cell imaging. The approach offers new insights for designing other fluorophores which emit red or near-infrared light and for devising technically simple ratiometric fluorescent sensors.

PbWoxT1 MRNA from Pear (Pyrus Betulaefolia) Undergoes Long-distance Transport Assisted by a Polypyrimidine Tract Binding Protein

The New Phytologist. Apr, 2016  |  Pubmed ID: 26661583

Little is known about the mechanisms by which mRNAs are transported over long distances in the phloem between the rootstock and the scion in grafted woody plants. We identified an mRNA in the pear variety 'Du Li' (Pyrus betulaefolia) that was shown to be transportable in the phloem. It contains a WUSCHEL-RELATED HOMEOBOX (WOX) domain and was therefore named Wox Transport 1 (PbWoxT1). A 548-bp fragment of PbWoxT1 is critical in long-distance transport. PbWoxT1 is rich in CUCU polypyrimidine domains and its mRNAs interact with a polypyrimidine tract binding protein, PbPTB3. Furthermore, the expression of PbWoxT1 significantly increased in the stems of wild-type (WT) tobacco grafted onto the rootstocks of PbWoxT1 or PbPTB3 co-overexpressing lines, but this was not the case in WT plants grafted onto PbWoxT1 overexpressing rootstocks, suggesting that PbPTB3 mediates PbWoxT1 mRNA long-distance transport. We provide novel information that adds a new mechanism with which to explain the noncell-autonomous manner of WOX gene function, which enriches our understanding of how WOX genes work in fruit trees and other species.

Coherent Transport Through Spin-crossover Magnet Fe2 Complexes

Nanoscale. Jan, 2016  |  Pubmed ID: 26647165

As one of the most promising building blocks in molecular spintronics, spin crossover (SCO) complexes have attracted increasing attention due to their magnetic bistability between the high-spin (HS) and low-spin (LS) states. Here, we explore the electronic structures and transport properties of SCO magnet Fe2 complexes with three different spin-pair configurations, namely [LS-LS], [LS-HS], and [HS-HS], by performing extensive density functional theory calculations combined with the non-equilibrium Green's function technique. Our calculations clearly reveal that the SCO magnet Fe2 complexes should display two-step spin transitions triggered by external stimuli, i.e. temperature or light, which confirm the previous phenomenological model and agree well with previous experimental measurements. Based on the calculated transport results, we observe a nearly perfect spin-filtering effect and negative differential resistance (NDR) behavior integrated in the SCO magnet Fe2 junction with the [HS-HS] configuration. The current through the [HS-HS] SCO magnet Fe2 complex under a small bias voltage is mainly contributed by the spin-down electrons, which is significantly larger than those of the [LS-LS] and [LS-HS] cases. The bias-dependent transmissions are responsible for the observed NDR effect. These theoretical findings suggest that SCO Fe2 complexes hold potential applications in molecular spintronic devices.

Entrapping a Group-VB Transition Metal, Vanadium, Within an Endohedral Metallofullerene: V(x)Sc(3-x)N@I(h)-C80 (x = 1, 2)

Journal of the American Chemical Society. Jan, 2016  |  Pubmed ID: 26645852

So far the entrapped metals for the isolated endohedral metallofullerenes (EMFs) are primarily limited to rare earth metals, whereas except group-IVB metals, whether it is possible to entrap other d-block transition metals remains unclear. Herein we report the successful entrapment of the group-VB transition metal vanadium(V) into fullerene cage, affording the heretofore unknown V-containing EMFs. Two novel V-containing EMFs--V(x)Sc(3-x)N@C80 (x = 1, 2)--were isolated, and their molecular structures were unambiguously determined by X-ray crystallography to be I(h)(7)-C80 cage entrapping the planar VSc2N/V2ScN clusters. V(x)Sc(3-x)N@I(h)(7)-C80 (x = 1, 2) were further characterized by UV-vis-NIR and ESR spectroscopies and electrochemistry, revealing that the electronic and magnetic properties of V(x)Sc(3-x)N@I(h)(7)-C80 (x = 1, 2) are tunable upon varying the number of entrapped V atoms (i.e., x value). The molecular structures and electronic properties of V(x)Sc(3-x)N@I(h)(7)-C80 (x = 1, 2) were further compared with those of the reported analogous EMFs based on lanthanide metals and the adjacent group-IVB transition metal Ti, revealing the peculiarity of the group-VB transition metal V-based EMFs.

Characterization of the Single Cycle Replication of HIV-1 Expressing Gaussia Luciferase in Human PBMCs, Macrophages, and in CD4(+) T Cell-grafted Nude Mouse

Journal of Virological Methods. Feb, 2016  |  Pubmed ID: 26640121

In this study, we have described a sensitive HIV-1 single cycle replicating virus that expresses a secreted Gaussia luciferase (Gluc) as a biomarker. This single cycle replicating virus was produced by the co-transfection of 293T cells with a multiple gene-deleted HIV provirus (ΔRI/ΔE/Gluc) and CMVin-Gag/Pol and viral envelope glycoprotein (Env) plasmids. The results showed that this HIV-1 virus efficiently infected and was restricted to one replication cycle in primary CD4+ T cells, macrophages and CD4+ T cell-grafted nude mouse. Because the viral genomic DNA lacks reverse transcriptase and integrase genes and has a partial deletion in the env gene, this trans-complemented virus could not be converted into the wild type virus after multiple passages in highly susceptible CD4+ C8166 T cells, demonstrating the safety of this system. Furthermore, infection with this virus was easily monitored by detecting the Gluc activity in the cell culture supernatants or in the animal peritoneal fluid or blood, which was shown to be more sensitive than the anti-p24 ELISA assay. This trans-complemented virus system is valuable for various HIV single cycle infection and viral expression studies in the laboratory where a biosafety level-3 containment facility is not accessible.

A Visualization Method Measuring the Performance of Biomarkers for Guiding Treatment Decisions

Pharmaceutical Statistics. Mar-Apr, 2016  |  Pubmed ID: 26632104

Biomarkers that predict efficacy and safety for a given drug therapy become increasingly important for treatment strategy and drug evaluation in personalized medicine. Methodology for appropriately identifying and validating such biomarkers is critically needed, although it is very challenging to develop, especially in trials of terminal diseases with survival endpoints. The marker-by-treatment predictiveness curve serves this need by visualizing the treatment effect on survival as a function of biomarker for each treatment. In this article, we propose the weighted predictiveness curve (WPC). Based on the nature of the data, it generates predictiveness curves by utilizing either parametric or nonparametric approaches. Especially for nonparametric predictiveness curves, by incorporating local assessment techniques, it requires minimum model assumptions and provides great flexibility to visualize the marker-by-treatment relationship. WPC can be used to compare biomarkers and identify the one with the highest potential impact. Equally important, by simultaneously viewing several treatment-specific predictiveness curves across the biomarker range, WPC can also guide the biomarker-based treatment regimens. Simulations representing various scenarios are employed to evaluate the performance of WPC. Application on a well-known liver cirrhosis trial sheds new light on the data and leads to discovery of novel patterns of treatment biomarker interactions.

DIRECT-ID: An Automated Method to Identify and Quantify Conformational Variations--application to β2 -adrenergic GPCR

Journal of Computational Chemistry. Feb, 2016  |  Pubmed ID: 26558323

The conformational dynamics of a macromolecule can be modulated by a number of factors, including changes in environment, ligand binding, and interactions with other macromolecules, among others. We present a method that quantifies the differences in macromolecular conformational dynamics and automatically extracts the structural features responsible for these changes. Given a set of molecular dynamics (MD) simulations of a macromolecule, the norms of the differences in covariance matrices are calculated for each pair of trajectories. A matrix of these norms thus quantifies the differences in conformational dynamics across the set of simulations. For each pair of trajectories, covariance difference matrices are parsed to extract structural elements that undergo changes in conformational properties. As a demonstration of its applicability to biomacromolecular systems, the method, referred to as DIRECT-ID, was used to identify relevant ligand-modulated structural variations in the β2 -adrenergic (β2 AR) G-protein coupled receptor. Micro-second MD simulations of the β2 AR in an explicit lipid bilayer were run in the apo state and complexed with the ligands: BI-167107 (agonist), epinephrine (agonist), salbutamol (long-acting partial agonist), or carazolol (inverse agonist). Each ligand modulated the conformational dynamics of β2 AR differently and DIRECT-ID analysis of the inverse-agonist vs. agonist-modulated β2 AR identified residues known through previous studies to selectively propagate deactivation/activation information, along with some previously unidentified ligand-specific microswitches across the GPCR. This study demonstrates the utility of DIRECT-ID to rapidly extract functionally relevant conformational dynamics information from extended MD simulations of large and complex macromolecular systems.

What Has Shaken the Determination of Medical Students to Become a Doctor?

Chinese Medical Journal. Apr, 2017  |  Pubmed ID: 28397733

Iterative Reconstruction for Sparse-view X-ray CT Using Alpha-divergence Constrained Total Generalized Variation Minimization

Journal of X-ray Science and Technology. Apr, 2017  |  Pubmed ID: 28387700

Accurate statistical model of the measured projection data is essential for computed tomography (CT) image reconstruction. The transmission data can be described by a compound Poisson distribution upon an electronic noise background. However, such a statistical distribution is numerically intractable for image reconstruction.

Association Between Phytosterol Intake and Colorectal Cancer Risk: a Case-control Study

The British Journal of Nutrition. Apr, 2017  |  Pubmed ID: 28382872

A study in rodent models showed that phytosterols protected against colon carcinogenesis, probably by inhibiting dysregulated cell cycle progression and inducing cellular apoptosis. However, epidemiological studies on the relationship between phytosterols and colorectal cancer risk are quite limited. The aim of this study was to investigate dietary phytosterol intake in relation to colorectal cancer risk in the Chinese population. A case-control study was conducted from July 2010 to June 2016, recruiting 1802 eligible colorectal cancer cases plus 1813 age (5-year interval) and sex frequency-matched controls. Dietary information was collected by using a validated FFQ. The OR and 95 % CI of colorectal cancer risk were assessed by multivariable logistic regression models. A higher total intake of phytosterols was found to be associated with a 50 % reduction in colorectal cancer risk. After adjusting for various confounders, the OR of the highest quartile intake compared with the lowest quartile intake was 0·50 (95 % CI 0·41, 0·61, P trend<0·01) for total phytosterols. An inverse association was also found between the consumption of β-sitosterol, campesterol, campestanol and colorectal cancer risk. However, stigmasterol intake was related to an increased risk of colorectal cancer. No statistically significant association was found between β-sitostanol and colorectal cancer risk. Stratified analysis by sex showed that the positive association of stigmasterol intake with colorectal cancer risk was found only in women. These data indicated that the consumption of total phytosterols, β-sitosterol, campesterol and campestanol is inversely associated with colorectal cancer risk in a Chinese population.

Relative Effectiveness of Adjuvant Chemotherapy for Invasive Lobular Compared with Invasive Ductal Carcinoma of the Breast

Cancer. Apr, 2017  |  Pubmed ID: 28382636

Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have distinct clinical, pathologic, and genomic characteristics. The objective of the current study was to compare the relative impact of adjuvant chemotherapy on the survival of patients with ILC versus those with IDC.

[Influence of Projection Data Correction on Digital Breast Tomosynthesis Imaging]

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Mar, 2017  |  Pubmed ID: 28377347

To investigate the effect of detector performance during digital breast tomography (DBT) projection data acquisition on reconstructed image quality.

Ambient Temperature and Cardiovascular Biomarkers in a Repeated-measure Study in Healthy Adults: A Novel Biomarker Index Approach

Environmental Research. Mar, 2017  |  Pubmed ID: 28359041

Associations of ambient temperature with cardiovascular morbidity and mortality have been well documented in numerous epidemiological studies, but the underlying pathways remain unclear. We investigated whether systemic inflammation, coagulation, systemic oxidative stress, antioxidant activity and endothelial function may be the mechanistic pathways associated with ambient temperature.

StMYB44 Negatively Regulates Phosphate Transport by Suppressing Expression of PHOSPHATE1 in Potato

Journal of Experimental Botany. Mar, 2017  |  Pubmed ID: 28338870

Phosphorus is an important macronutrient for plant growth, but often deficient in soil. To understand the molecular basis of the complex responses of potato (Solanum tuberosum L.) to phosphate (Pi) deficiency stress, the RNA-Seq approach was taken to identify genes responding to Pi starvation in potato roots. A total of 359 differentially expressed genes were identified, among which the Solanum tuberosum transcription factor gene MYB44 (StMYB44) was found to be down-regulated by Pi starvation. StMYB44 was ubiquitously expressed in potato tissues and organs, and StMYB44 protein was exclusively localized in the nucleus. Overexpression of StMYB44 in potato resulted in lower accumulation of Pi in shoots. Transcriptomic analysis indicated that the abundance of S. tuberosum PHOSPHATE1 (StPHO1), a Pi transport-related gene, was reduced in StMYB44 overexpression lines. In contrast, knock-out of StMYB44 by a CRISPR/Cas9 system failed to increase transcription of StPHO1. Moreover, StMYB44 was found to interact in the nucleus with AtWRKY6, a known Arabidopsis transcription factor directly regulating PHO1 expression, and StWRKY6, indicating that StMYB44 could be a member of the regulatory complex controlling transcription of StPHO1. Taken together, our study demonstrates that StMYB44 negatively regulates Pi transport in potato by suppressing StPHO1 expression.

Dynamic and Specific Immune Responses Against Multiple Tumor Antigens Were Elicited in Patients with Hepatocellular Carcinoma After Cell-based Immunotherapy

Journal of Translational Medicine. Mar, 2017  |  Pubmed ID: 28330473

Hepatocellular carcinoma (HCC) is one of the most common cancers in China and frequently occurs with chronic hepatitis B virus infection. To investigate whether cell-based cancer immunotherapy induces tumor specific immune responses in patients with HCC and provides clinical benefits, as well as to elucidate the most immunogenic tumor associated antigens (TAAs), multiple antigen stimulating cellular therapy (MASCT) was applied in addition to standard of care.

CTLA-4 Gene Polymorphisms Associate with Efficacy of Postoperative Radioiodine-131 for Differentiated Thyroid Carcinoma

Future Oncology (London, England). Mar, 2017  |  Pubmed ID: 28326838

To investigate the association of CTLA-4 polymorphisms with efficacy of postoperative radioiodine-131 (I-131) treatment for differentiated thyroid carcinoma (DTC).

In Vitro Preparation and Crystallization of Vertebrate Telomerase Subunits

Methods in Molecular Biology (Clifton, N.J.). 2017  |  Pubmed ID: 28324508

Telomerase is a unique reverse transcriptase that replicates the telomeric DNA at most eukaryotic chromosomal ends. The telomerase consists of the catalytic protein subunit TERT and the RNA component TR that provides the template for telomeric DNA synthesis. In vitro reconstitution of telomerase core components in large quantity is the prerequisite to studying the catalytic mechanisms of telomerase at the structural level; however, large-scale preparation of recombinant telomerase, especially that of higher eukaryotes, has been a big challenge for a long time. It has been known that the CR4/5 domain of the vertebrate TR binds to the TRBD domain of TERT and the interaction is essential to the assembly and enzymatic activity of telomerase. We assembled the TRBD-CR4/5 ribonucleoprotein complex of the medaka fish telomerase in vitro and determined its atomic structure through X-ray crystallography. Our study provides the structural insight into the RNA-protein recognition mechanism that is common to most eukaryotic telomerase. The methods of our study are also applicable to large-scale preparations of other ribonucleoprotein complexes for structural studies.

Gadolinium-Naive Nephrogenic Systemic Fibrosis of Breast Mimicking Inflammatory Breast Carcinoma

The American Journal of Dermatopathology. Apr, 2017  |  Pubmed ID: 28323787

Characterization of Dormant and Active Human Cancer Cells by Quantitative Phase Imaging

Cytometry. Part A : the Journal of the International Society for Analytical Cytology. Mar, 2017  |  Pubmed ID: 28314083

The switch of tumor cells from a dormant, non-angiogenic phenotype to an active, angiogenic phenotype is a critical step in early cancer progression. To date, relatively little is known about the cellular behaviors of angiogenic and non-angiogenic tumor cell phenotypes. In this study, holographic imaging cytometry, a quantitative phase imaging (QPI) technique was used to continuously and non-invasively analyze, quantify, and compare a panel of fundamental cellular behaviors of angiogenic and non-angiogenic human osteosarcoma cells (KHOS) in a simple and economical way. Results revealed that angiogenic KHOS cells (KHOS-A) have significantly higher cell motility speeds than their non-angiogenic counterpart (KHOS-N) while no difference in their cell proliferation rates and cell cycle lengths were observed. KHOS-A cells were also found to have significantly smaller cell areas and greater cell optical thicknesses when compared with the non-angiogenic KHOS-N cells. No difference in average cell volumes was observed. These studies demonstrate that the morphology and behavior of angiogenic and non-angiogenic cells can be continuously, efficiently, and non-invasively monitored using a simple, quantitative, and economical system that does not require tedious and time-consuming assays to provide useful information about tumor dormancy. © 2017 International Society for Advancement of Cytometry.

Polymorphisms and Pharmacogenomics for the Toxicity of Methotrexate Monotherapy in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis

Medicine. Mar, 2017  |  Pubmed ID: 28296761

Methotrexate (MTX) is widely used and considered a first-line disease modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). However, 10% to 30% of patients discontinue therapy within a year of starting the treatment, usually because of undesirable side effects. Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX toxicity in RA patients, although inconsistent results have been reported.

Pulse Pressure, Instead of Brachium-Ankle Pulse Wave Velocity, is Associated with Reduced Kidney Function in a Chinese Han Population

Kidney & Blood Pressure Research. Mar, 2017  |  Pubmed ID: 28291958

In this study, we aim to investigate the association between renal function and arterial stiffness in a Chinese Han population, and further to discuss the effects of smoking on renal function.

Variation in Aedes Aegypti Mosquito Competence for Zika Virus Transmission

Emerging Infectious Diseases. Apr, 2017  |  Pubmed ID: 28287375

To test whether Zika virus has adapted for more efficient transmission by Aedes aegypti mosquitoes, leading to recent urban outbreaks, we fed mosquitoes from Brazil, the Dominican Republic, and the United States artificial blood meals containing 1 of 3 Zika virus strains (Senegal, Cambodia, Mexico) and monitored infection, dissemination, and virus in saliva. Contrary to our hypothesis, Cambodia and Mexica strains were less infectious than the Senegal strain. Only mosquitoes from the Dominican Republic transmitted the Cambodia and Mexica strains. However, blood meals from viremic mice were more infectious than artificial blood meals of comparable doses; the Cambodia strain was not transmitted by mosquitoes from Brazil after artificial blood meals, whereas 61% transmission occurred after a murine blood meal (saliva titers up to 4 log 10 infectious units/collection). Although regional origins of vector populations and virus strain influence transmission efficiency, Ae. aegypti mosquitoes appear to be competent vectors of Zika virus in several regions of the Americas.

Impact of CRP Gene and Additional Gene-smoking Interaction on Ischemic Stroke in a Chinese Han Population

Neurological Research. Mar, 2017  |  Pubmed ID: 28287042

To investigate the association of C-reactive protein (CRP) gene single nucleotide polymorphisms (SNPs), additional gene-gene, and gene-smoking interaction with ischemic stroke (IS) risk.

Engineering the Ribosomal DNA in a Megabase Synthetic Chromosome

Science (New York, N.Y.). Mar, 2017  |  Pubmed ID: 28280149

We designed and synthesized a 976,067-base pair linear chromosome, synXII, based on native chromosome XII in Saccharomyces cerevisiae SynXII was assembled using a two-step method, specified by successive megachunk integration and meiotic recombination-mediated assembly, producing a functional chromosome in S. cerevisiae. Minor growth defect "bugs" detected in synXII, caused by deletion of tRNA genes, were rescued by introducing an ectopic copy of a single tRNA gene. The ribosomal gene cluster (rDNA) on synXII was left intact during the assembly process and subsequently replaced by a modified rDNA unit used to regenerate rDNA at three distinct chromosomal locations. The signature sequences within rDNA, which can be used to determine species identity, were swapped to generate a Saccharomyces synXII strain that would be identified as Saccharomyces bayanus by standard DNA barcoding procedures.

Excessive Fruit Consumption During the Second Trimester is Associated with Increased Likelihood of Gestational Diabetes Mellitus: a Prospective Study

Scientific Reports. Mar, 2017  |  Pubmed ID: 28272552

This study aimed to investigate the association between fruit consumption during the second trimester and the occurrence of gestational diabetes mellitus (GDM). A prospective study with 772 female participants was conducted in China from April 2013 to August 2014. Dietary intake was assessed in face-to-face and telephone interviews using a 3-day food record. GDM was ascertained using a standard 75 g 2 hour oral glucose tolerance test. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for various confounders. Of the 772 participants, 169 were diagnosed with GDM during the period under study. Greater total fruit consumption during the second trimester was associated with a higher likelihood of GDM (highest vs. lowest quartile: adjusted OR4.82, 95% CI 2.38 to 9.76). Fruits with a moderate or high glycaemic index (GI) were positively associated with the occurrence of GDM. Fruit subgroups were also categorised by polyphenol content, and tropical-fruit and citrus-fruit consumption was found to be positively related to the occurrence of GDM. These findings suggest that the excessive consumption of fruit, especially fruit with moderate or high GI values, tropical-fruit and citrus-fruit, increases the likelihood of GDM.

Polymorphisms and Pharmacogenomics for the Clinical Efficacy of Methotrexate in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis

Scientific Reports. Mar, 2017  |  Pubmed ID: 28266606

Methotrexate (MTX) is widely used and considered a first-line disease modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX effectiveness in RA patients, although inconsistent results have been reported. A systematic review and meta-analysis were performed to identify genetic variants associated with MTX efficacy. A total of 30 publications that included 34 genes and 125 SNPs associated with the transporters, enzymes, and metabolites of MTX or the progression of RA were included in the systematic review (SR), and 21 studies were included in 9 meta-analyses. Associations between MTX response in RA patients in MTHFR 1298A > C (rs1801131), ATIC 347C > G (rs2372536), RFC-1 80G > A (rs1051266), SLC19A1 A > G (rs2838956) and SLC19A1 G > A (rs7499) genetic polymorphisms were found, but not observed between the MTHFR 677C > T (rs1801133), TYMS 28 bp VNTR (rs34743033), MTRR 66A > G (rs1801394), and ABCB1 3435C > T (rs1045642). However, for the polymorphisms not being associated following meta-analysis could still be associated if larger cohorts were used, and studies of other polymorphisms are necessary in large cohorts and a rigorous way, which may provide more accurate results for the effect of the gene polymorphisms on the MTX response.

NCOA1 is a Novel Susceptibility Gene for Multiple Myeloma in the Chinese Population: A Case-control Study

PloS One. 2017  |  Pubmed ID: 28264017

Multiple myeloma (MM) is an incurable malignancy of mature B-lymphoid cells, and its pathogenesis is only partially understood. Previous studies have demonstrated that a number of Non-Hodgkin Lymphoma (NHL) associated genes also show susceptibility to MM, suggesting malignancies originating from B cells may share similar genetic susceptibility. Several recent large-scale genome-wide association studies (GWAS) have identified HLA-I, HLA-II, CXCR5, ETS1, LPP and NCOA1 genes as genetic risk factors associated with NHL, and this study aimed to investigate whether these genes polymorphisms confer susceptibility with MM in the Chinese Han population. In 827 MM cases and 709 healthy controls of Chinese Han, seven single nucleotide polymorphisms (SNPs) in the HLA-I region (rs6457327), the HLA-II region (rs2647012 and rs7755224), the CXCR5 gene (rs4938573), the ETS1 gene (rs4937362), the LPP gene (rs6444305), and the NCOA1 region (rs79480871) were genotyped using the Sequenom platform. Our study indicated that genotype and allele frequencies of rs79480871 showed strong associations with MM patients (pa = 3.5×10-4 and pa = 1.5×10-4), and the rs6457327 genotype was more readily associated with MM patients than with controls (pa = 4.9×10-3). This study was the first to reveal the correlation between NCOA1 gene polymorphisms and MM patients, indicating that NCOA1 might be a novel susceptibility gene for MM patients in the Chinese Han population.

Synthesis of Hydrophilic and Conductive Molecularly Imprinted Polyaniline Particles for the Sensitive and Selective Protein Detection

Biosensors & Bioelectronics. Feb, 2017  |  Pubmed ID: 28249205

In this work, a novel kind of water-dispersible molecular imprinted conductive polyaniline particles was prepared through a facile and efficient macromolecular co-assembly of polyaniline with amphiphilic copolymer, and applied as the molecular recognition element to construct protein electrochemical sensor. In our strategy, an amphiphilic copolymer P(AMPS-co-St) was first synthesized using 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and styrene (St) as monomer, which could co-assemble with PANI in aqueous solution to generate PANI particles driven by the electrostatic interaction. During this process, ovalbumin (OVA) as template protein was added and trapped into the PANI NPs particles owing to their interactions, resulting in the formation of molecular imprinted polyaniline (MIP-PANI) particles. When utilizing the MIP-PANI particles as recognition element, the resultant imprinted PANI sensor not only exhibited good selectivity toward template protein (the imprinting factor α is 5.31), but also a wide linear range over OVA concentration from 10(-11) to 10(-6)mgmL(-1) with a significantly lower detection limit of 10(-12)mgmL(-1), which outperformed most of reported OVA detecting methods. In addition, an ultrafast response time of less than 3min has also been demonstrated. The superior performance is ascribed to the water compatibility, large specific surface area of PANI particles and the electrical conductivity of PANI which provides a direct path for the conduction of electrons from the imprinting sites to the electrode surface. The outstanding sensing performance combined with its facile, quick, green preparation procedure as well as low production cost makes the MIP-PANI particles attractive in specific protein recognition and sensing.

Preoperative Statin Treatment for the Prevention of Acute Kidney Injury in Patients Undergoing Cardiac Surgery: A Meta-Analysis of Randomised Controlled Trials

Heart, Lung & Circulation. Feb, 2017  |  Pubmed ID: 28242291

The effect of preoperative statin treatment (PST) on the risk of postoperative acute kidney injury (AKI) after cardiac surgery remains controversial. We performed a meta-analysis of randomised controlled trials (RCT) to investigate whether PST could improve the renal outcomes in patients undergoing cardiac surgery.

A Dual-label Time-resolved Fluorescence Immunoassay for the Simultaneous Determination of Ferritin and β2 -microglobulin

Journal of Clinical Laboratory Analysis. Feb, 2017  |  Pubmed ID: 28230288

Lymphocytic leukemia is a kind of primary malignant tumor of hematopoietic tissue. The aim was to establish a dual-label time-resolved fluorescence immunoassay (TRFIA) for the simultaneous determination of ferritin (FER) and β2 -microglobulin (β2 -MG) for the early screening and follow-up surveillance of lymphocytic leukemia.

Bioinspired Design of a Robust Elastomer with Adaptive Recovery Via Triazolinedione Click Chemistry

Macromolecular Rapid Communications. Apr, 2017  |  Pubmed ID: 28199759

It is a significant but challenging task to simultaneously reinforce and functionalize diene rubbers. Inspired by "sacrificial bonds", the authors engineer sacrificial hydrogen bonds formed by pendent urazole groups in crosslinked solution-polymerized styrene butadiene rubber (SSBR) via triazolinedione click chemistry. This post-crosslinking modification reveals the effects of the sacrificial bonds based on a consistent covalent network. The "cage effect" of the pre-crosslinked network facilitates the heterogeneous distribution of urazole groups, leading to the formation of hydrogen-bonded multiplets. These multiplets further aggregate into clusters with vicinal trapped polymer segments that form microphase separation from the SSBR matrix with a low content of urazole groups. The clusters based on hydrogen bonds, serving as sacrificial bonds, promote energy dissipation, significantly improving the mechanical properties of the modified SSBR, and enable an additional wide transition temperature region above room temperature, which endows the modified SSBR with promising triple-shape memory behavior.

Double Recognition and Selective Extraction of Glycoprotein Based on the Molecular Imprinted Graphene Oxide and Boronate Affinity

ACS Applied Materials & Interfaces. Mar, 2017  |  Pubmed ID: 28191926

Specific recognition and separation of glycoproteins from complex biological solutions is very important in clinical diagnostics considering the close relationship between glycoproteins with the occurrence of diverse diseases, but the lack of materials with high selectivity and superior capture capacity still makes it a challenge. In this work, graphene oxide (GO) based molecularly imprinted polymers (MIPs) possessing double recognition abilities have been synthesized and applied as highly efficient adsorbents for glycoprotein recognition and separation. Boronic acid functionalized graphene oxide (GO-APBA) was first prepared and a template glycoprotein (ovalbumin, OVA) was then immobilized onto the surface of GO-APBA through boronate affinity. An imprinting layer was subsequently deposited onto GO-APBA surface by a sol-gel polymerization of organic silanes in aqueous solution. After the removal of the template glycoprotein, 3D cavities with double recognition abilities toward OVA were obtained in the as-prepared imprinted materials (GO-APBA/MIPs) because of the combination of boronate affinity and molecularly imprinted spatial matched cavities. The obtained GO-APBA/MIPs exhibited superior specific recognition toward OVA with imprinted factor (α) as high as 9.5, significantly higher than the corresponding value (4.0) of GO/MIPs without the introduction of boronic acid groups. Meanwhile, because of the synergetic effect of large surface area of graphene and surface imprinting, high binding capacity and fast adsorption/elution rate of GO-APBA/MIPs toward OVA were demonstrated and the saturation binding capacity of GO-APBA/MIPs could reach 278 mg/g within 40 min. The outstanding recognizing behavior (high adsorption capacity, highly specific recognition, and rapid binding rate) coupled to the facile and environmentally friendly preparation procedure makes GO-APBA/MIPs promising in the recognition, separation, and analysis of glycoproteins in clinics in the future.

[Diagnosis of a Case with Oculocutaneous Albinism Type Ⅲ with Next Generation Exome Capture Sequencing]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics. Feb, 2017  |  Pubmed ID: 28186599

To explore the clinical and genetic features of a Chinese boy with oculocutaneous albinism.

RECQL5 Plays Co-operative and Complementary Roles with WRN Syndrome Helicase

Nucleic Acids Research. Feb, 2017  |  Pubmed ID: 28180303

Metabolic Changes in Normal-appearing White Matter in Patients with Neuromyelitis Optica and Multiple Sclerosis: a Comparative Magnetic Resonance Spectroscopy Study

Acta Radiologica (Stockholm, Sweden : 1987). Jan, 2017  |  Pubmed ID: 28173728

Background Previous studies with a small sample size have not reported metabolic changes in neuromyelitis optica (NMO). Metabolic changes, such as decreased N-acetylaspartate (NAA), are well-established in patients with multiple sclerosis (MS). It remains unknown whether different patterns of metabolic changes occur in NMO and MS. Purpose To investigate the metabolic changes in normal-appearing white matter (NAWM) in NMO, compared with MS patients and healthy controls (HC), and correlate these changes with clinical disability. Material and Methods We recruited 27 patients with NMO, 24 patients with MS, and 24 HC. Each participant underwent chemical shift imaging with a 1H-MR spectroscopy operating in a 1.5 T magnetic resonance imaging (MRI) scanner. The absolute concentrations of NAA, choline (Cho), creatine (Cr) as well as the metabolite ratios of NAA/Cr, Cho/Cr, and NAA/Cho were measured and compared among the groups. The correlations between the metabolic concentrations, disease duration, and clinical disability (Expanded Disability Status Scale, EDSS) were further explored. Results Compared with HC, a mild increase of Cho without significant NAA changes was observed in NMO patients, while both a significant reduction of NAA and an increase of Cho were observed in MS patients. The absolute concentration of NAA and NAA/Cho ratio were significantly decreased in MS patients in a direct comparison with NMO patients. In MS patients, the EDSS was correlated with the NAA/Cr and Cho/Cr ratios. Conclusion A reduction of NAA was not observed in NMO, implying axonal or neuronal damage may be absent in NAWM for NMO, which is different from MS. A mild increase in Cho was observed in NAWM of NMO patients, suggesting that subtle metabolic changes occur in NMO.

B7-H3 Augments Inflammatory Responses and Exacerbates Brain Damage Via Amplifying NF-κB P65 and MAPK P38 Activation During Experimental Pneumococcal Meningitis

PloS One. 2017  |  Pubmed ID: 28141831

The costimulatory protein B7-H3 has been shown to play a contributory role in the development and progression of experimental pneumococcal meningitis by augmentation of the innate immunity-associated inflammatory response via a TLR2-dependent manner. This study aimed to clarify the component(s) of TLR2-mediated signal transduction pathways responsible for B7-H3-augmented inflammatory response and subsequent brain damage during experimental pneumococcal meningitis. Administration of B7-H3 did not augment expression of TLR2 and other TLR2 upstream components, but led to an enhanced formation of MyD88-IRAK immunocomplex in the brain of S. pneumoniae-infected mice. Furthermore, B7-H3 substantially augmented S. pneumoniae-induced activation of TLR2 downstream NF-κB p65 and MAPK p38 pathways in the brain of S. pneumoniae-infected mice. Notably, blockage of NF-κB p65 and/or MAPK p38 with their specific inhibitors strongly attenuated B7-H3-amplified inflammatory response with significantly reduced proinflammatory cytokine and chemokine production, and markedly ameliorated B7-H3-exacerbated disruption of blood-brain barrier and severity of disease status in S. pneumoniae-infected mice. These results indicate that targeting NF-κB p65 and/or MAPK p38 may represent a promising therapeutic option for amelioration of overwhelming inflammatory response-associated brain injury frequently observed during pneumococcal meningitis.

Role of Gambogic Acid and NaI(131) in A549/DDP Cells

Oncology Letters. Jan, 2017  |  Pubmed ID: 28123519

Resistance to platinum in tumor tissue is a considerable barrier against effective lung cancer treatment. Radionuclide therapy is the primary adjuvant treatment, however, the toxic side effects limit its dosage in the clinical setting. Therefore, the present study aimed to determine whether an NaI(131) radiosensitizer could help reduce the toxic side effects of radionuclide therapy. In vitro experiments were conducted to determine whether NaI(131) can inhibit platinum resistance in A549/DDP cells, which are cisplatin-resistant non-small cell lung cancer cells, and whether gambogic acid (GA) is an effective NaI(131) radiosensitizer. Cell proliferation following drug intervention was analyzed using MTT and isobolographic analysis. Apoptosis was assessed by flow cytometry. In addition, the mechanisms of drug intervention were analyzed by measuring the expression of P-glycoprotein (P-gP), B cell lymphoma 2 (Bcl-2), Bcl2-associated X protein (Bax) and P53 using western blot analysis and immunocytochemistry. According to isobolographic analysis, a low concentration of NaI(131) combined with GA had a synergistic effect on the inhibition of A549/DDP cell proliferation, which was consistent with an increased rate of apoptosis. Furthermore, the overexpression of Bax, and the downregulation of P-gP, P53 and Bcl-2 observed demonstrated the potential mechanism(s) of NaI(131) and GA intervention. NaI(131) may induce apoptosis in A549/DDP cells by regulating apoptosis-related proteins. A low concentration combination of NaI(131) and GA was able to significantly inhibit A549/DDP cell proliferation and induce cell apoptosis. Thus, the two drugs appear to have a synergistic effect on apoptosis of A549/DDP cells.

A Case-control Study of Risk Sources for Severe Fever with Thrombocytopenia Syndrome in Hubei Province, China

International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases. Feb, 2017  |  Pubmed ID: 28088586

Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease caused by a novel bunyavirus, was discovered in rural areas of Central China in 2009.

Flow Injection Microfluidic Device with On-line Fluorescent Derivatization for the Determination of Cr(III) and Cr(VI) in Water Samples After Solid Phase Extraction

Analytica Chimica Acta. Feb, 2017  |  Pubmed ID: 28088281

In this paper, a rapid and simple method using magnetic multi-walled carbon nanotubes (MWCNTS), as a solid-phase extraction (SPE) sorbent, was successfully developed for extraction and preconcentration trace amounts of Cr(III) in water samples. The synthesized magnetic-MWCNTs nanocomposite was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). A rhodamine derivative (R1) was synthesized and characterized as a highly selective and sensitive fluorescent derivatizing agent for Cr(III). After SPE procedure, Cr(III) analysis was performed by flow injection microfluidic chip with on-line fluorescent derivatization and laser-induced fluorescence (LIF) spectroscopy detection. The parameters, which affected the efficiency of the developed method were investigated and optimized. Under the optimized conditions, the method exhibited a linear dynamic range of 0-10.0 nM, with a detection limit of 0.094 nM and an enrichment factor of 38. Furthermore, real water samples were analyzed and good recoveries were obtained from 91.0 to 101.6%.

Screening Active Compounds from Corydalis Yanhusuo by Combining High Expression VEGF Receptor HEK293 Cell Membrane Chromatography with HPLC - ESI - IT - TOF - MSn Method

Journal of Pharmaceutical and Biomedical Analysis. Mar, 2017  |  Pubmed ID: 28081499

Corydalis Thizoma,or Yuanhu in China, is a common herbal drug used for thousands of years as analgesic in Chinese medicine that has been reported to have potential anti-angiogenic effects. In this study, a VEGFR/cell membrane chromatography (VEGFR/CMC) coupled with HPLC- ESI-IT-TOF-MSn system was developed and successfully applied for identifying active components from YuanHu extract acting on VEGFR. We identified tetrahydropalmatine and corydaline as bioactive components with VEGFR activity, thus confirming their inhibitory activity on VEGFR engineered HEK293 cell growth by MTT assay. The activity of tetrahydropalmatine and corydaline was compared with the positive control sorafenib in a range of concentration from 6.25 to 50.0μM, showing a dose-dependent inhibitory trend. These results indicate that the VEGFR/CMC coupled with HPLC- ESI-IT-TOF-MSn system can purify and identify specific bioactive components from complex systems, thus representing a promising tool for screening molecules active towards VEGFR from natural herbs.

An Estimation of Hybrid Quantum Mechanical Molecular Mechanical Polarization Energies for Small Molecules Using Polarizable Force-Field Approaches

Journal of Chemical Theory and Computation. Feb, 2017  |  Pubmed ID: 28081366

In this work, we report two polarizable molecular mechanics (polMM) force field models for estimating the polarization energy in hybrid quantum mechanical molecular mechanical (QM/MM) calculations. These two models, named the potential of atomic charges (PAC) and potential of atomic dipoles (PAD), are formulated from the ab initio quantum mechanical (QM) response kernels for the prediction of the QM density response to an external molecular mechanical (MM) environment (as described by external point charges). The PAC model is similar to fluctuating charge (FQ) models because the energy depends on external electrostatic potential values at QM atomic sites; the PAD energy depends on external electrostatic field values at QM atomic sites, resembling induced dipole (ID) models. To demonstrate their uses, we apply the PAC and PAD models to 12 small molecules, which are solvated by TIP3P water. The PAC model reproduces the QM/MM polarization energy with a R(2) value of 0.71 for aniline (in 10,000 TIP3P water configurations) and 0.87 or higher for other 11 solute molecules, while the PAD model has a much better performance with R(2) values of 0.98 or higher. The PAC model reproduces reference QM/MM hydration free energies for 12 solute molecules with a RMSD of 0.59 kcal/mol. The PAD model is even more accurate, with a much smaller RMSD of 0.12 kcal/mol, with respect to the reference. This suggests that polarization effects, including both local charge distortion and intramolecular charge transfer, can be well captured by induced dipole type models with proper parametrization.

Acetylation Promotes TyrRS Nuclear Translocation to Prevent Oxidative Damage

Proceedings of the National Academy of Sciences of the United States of America. Jan, 2017  |  Pubmed ID: 28069943

Tyrosyl-tRNA synthetase (TyrRS) is well known for its essential aminoacylation function in protein synthesis. Recently, TyrRS has been shown to translocate to the nucleus and protect against DNA damage due to oxidative stress. However, the mechanism of TyrRS nuclear localization has not yet been determined. Herein, we report that TyrRS becomes highly acetylated in response to oxidative stress, which promotes nuclear translocation. Moreover, p300/CBP-associated factor (PCAF), an acetyltransferase, and sirtuin 1 (SIRT1), a NAD(+)-dependent deacetylase, regulate the nuclear localization of TyrRS in an acetylation-dependent manner. Oxidative stress increases the level of PCAF and decreases the level of SIRT1 and deacetylase activity, all of which promote the nuclear translocation of hyperacetylated TyrRS. Furthermore, TyrRS is primarily acetylated on the K244 residue near the nuclear localization signal (NLS), and acetylation inhibits the aminoacylation activity of TyrRS. Molecular dynamics simulations have shown that the in silico acetylation of K244 induces conformational changes in TyrRS near the NLS, which may promote the nuclear translocation of acetylated TyrRS. Herein, we show that the acetylated K244 residue of TyrRS protects against DNA damage in mammalian cells and zebrafish by activating DNA repair genes downstream of transcription factor E2F1. Our study reveals a previously unknown mechanism by which acetylation regulates an aminoacyl-tRNA synthetase, thus affecting the repair pathways for damaged DNA.

Impact of Air Pollutants on Outpatient Visits for Acute Respiratory Outcomes

International Journal of Environmental Research and Public Health. Jan, 2017  |  Pubmed ID: 28067786

The air pollution in China is a severe problem. The aim of our study was to investigate the impact of air pollutants on acute respiratory outcomes in outpatients. Outpatient data from 2 December 2013 to 1 December 2014 were collected, as well as air pollutant data including ozone (O₃), nitrogen dioxide (NO₂), carbon monoxide (CO), sulfur dioxide (SO₂), and particulate matter (PM2.5 and PM10). We screened six categories of acute respiratory outcomes and analyzed their associations with different air pollutant exposures, including upper respiratory tract infection (URTI), acute bronchitis (AB), community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD), acute exacerbation of asthma (AE-asthma), and acute exacerbation of bronchiectasis (AEBX). A case-crossover design with a bidirectional control sampling approach was used for statistical analysis. A total of 57,144 patients were enrolled for analysis. PM2.5, PM10, NO₂, SO₂, and CO exposures were positively associated with outpatient visits for URTI, AB, CAP, and AEBX. PM10, SO₂, and CO exposures were positively associated with outpatient visits for AECOPD. Exposure to O₃ was positively associated with outpatient visits for AE-asthma, but negatively associated with outpatient visits for URTI, CAP, and AEBX. In conclusion, air pollutants had acute effects on outpatient visits for acute respiratory outcomes, with specific outcomes associated with specific pollutants.

Formation of Hexagonal-Close Packed (HCP) Rhodium As a Size Effect

Journal of the American Chemical Society. Jan, 2017  |  Pubmed ID: 28045542

Previous studies on the structural and functional properties of rhodium are based on the face-centered-cubic (fcc) structure in the bulk form. Here we report the first discovery of the hexagonal-close packed (hcp) rhodium in the nanoparticle form. The hcp Rh can be directly synthesized by solvothermal reaction or by electron-beam induced decomposition of Rh monolayers. The hcp Rh nanoparticles are stable under electron beam irradiation. Compared with the fcc structure, the hcp Rh nanoparticles show a large lattice expansion (6% larger atomic volume). The first-principles calculations suggest that the lower surface energy of hcp Rh leads to the size effect in the crystal structure.

A Novel Technique of Inserting Pancreaticogastrostomy with Duct-to-mucosa Anastomosis Can Potentially Reduce Postoperative Pancreatic Fistula

The Journal of Surgical Research. Mar, 2017  |  Pubmed ID: 28032574

We describe our novel technique of inserting pancreaticogastrostomy (IPG) after pancreaticoduodenectomy. In our technique, the seromuscular and mucosal layers of the posterior gastric wall are separated to create a mucosal pouch. A duct-to-mucosa anastomosis is performed through a small incision in the mucosal layer. An inner suture at the seromuscular-mucosal margin incorporating the pancreatic parenchyma and an outer suture on the exterior margin of the seromuscular layer to wrap the pouch around the pancreas are placed to complete the IPG.

Improving Sensitivity and Specificity of Capturing and Detecting Targeted Cancer Cells with Anti-biofouling Polymer Coated Magnetic Iron Oxide Nanoparticles

Colloids and Surfaces. B, Biointerfaces. Feb, 2017  |  Pubmed ID: 28029547

Detecting circulating tumor cells (CTCs) with high sensitivity and specificity is critical to management of metastatic cancers. Although immuno-magnetic technology for in vitro detection of CTCs has shown promising potential for clinical applications, the biofouling effect, i.e., non-specific adhesion of biomolecules and non-cancerous cells in complex biological samples to the surface of a device/probe, can reduce the sensitivity and specificity of cell detection. Reported herein is the application of anti-biofouling polyethylene glycol-block-allyl glycidyl ether copolymer (PEG-b-AGE) coated iron oxide nanoparticles (IONPs) to improve the separation of targeted tumor cells from aqueous phase in an external magnetic field. PEG-b-AGE coated IONPs conjugated with transferrin (Tf) exhibited significant anti-biofouling properties against non-specific protein adsorption and off-target cell uptake, thus substantially enhancing the ability to target and separate transferrin receptor (TfR) over-expressed D556 medulloblastoma cells. Tf conjugated PEG-b-AGE coated IONPs exhibited a high capture rate of targeted tumor cells (D556 medulloblastoma cell) in cell media (58.7±6.4%) when separating 100 targeted tumor cells from 1×10(5) non-targeted cells and 41 targeted tumor cells from 100 D556 medulloblastoma cells spiked into 1mL blood. It is demonstrated that developed nanoparticle has higher efficiency in capturing targeted cells than widely used micron-sized particles (i.e., Dynabeads(®)).

Zika Virus Vector Competency of Mosquitoes, Gulf Coast, United States

Emerging Infectious Diseases. Mar, 2017  |  Pubmed ID: 28005002

Zika virus has recently spread throughout the Americas. Although Aedes aegypti mosquitoes are considered the primary vector, Culex quinquefasciatus and mosquitoes of other species may also be vectors. We tested Cx. quinquefasciatus and Ae. taeniorhynchus mosquitoes from the US Gulf Coast; both were refractory to infection and incapable of transmission.

Rheological Properties of Nanocrystalline Cellulose Suspensions

Carbohydrate Polymers. Feb, 2017  |  Pubmed ID: 27987931

Rheological behavior, including linear and nonlinear, as well as transient rheology of nanocrystalline cellulose (NCC) suspensions was studied in this work. Two kinds of polymer solutions, aqueous poly(vinyl alcohol) (PVA) with flexible chain structure and aqueous carboxymethyl cellulose (CMC) with semi-rigid chain structure, were used as the suspension media to further explore the role that the interactions among NCC and polymers played during shear flow. The results reveal that NCC has lower values of percolation threshold in the PVA solution than in the CMC one during small amplitude oscillatory shear (SAOS) flow because the flexible PVA chain has higher adsorbed level onto NCC particles than the negatively charged semi-rigid CMC chain, which is further confirmed by the Fourier transformed infrared (FT-IR) spectroscopy tests. As a result, the NCC suspension shows a weak strain overshoot in PVA solution during large amplitude oscillatory shear (LAOS) flow, which cannot be seen on the one in CMC solution. During startup shear flow, both of these two suspensions show evident stress overshoot behavior with the strain-scaling characteristics, indicating the formation of ordered long-term structure of rod-like NCC particles with self-similarity during flow. However, NCC suspension have far stronger stress overshoot response in CMC solution relative to the one in PVA solution. A possible synergy mechanism between NCC and CMC chain is hence proposed.

Silver Nanoparticles Induce Oocyte Maturation in Zebrafish (Danio Rerio)

Chemosphere. Mar, 2017  |  Pubmed ID: 27974271

Public concern regarding silver nanoparticles (AgNPs) in the environment has been increasing since they can cause adverse effects in some aquatic species. However, few data are actually available on the effects of AgNPs on the germ cells. In the present study, we used the zebrafish ovarian follicle as a model to assess the potentially adverse effects of AgNPs on oocyte maturation (germinal vesicle breakdown, GVBD) in vitro. Similar to the maturation inducing hormone (17α, 20β-dihydroxy-4-pregnen-3-one), AgNPs induced GVBD, and reduced the total cyclic adenosine monophosphate (cAMP) concentration in zebrafish ovarian follicles. The results from transmission electron microscope observation and Hoechst 33342 staining clearly indicated that AgNPs induced apoptosis in ovarian follicle cells surrounding the oocyte. Similar to AgNPs, AgNO3 also induced GVBD, decreased cAMP concentration and induced apoptosis of ovarian follicle cells. However, the results from gene expression analysis showed that transcript levels of oxidative stress related genes were more sensitive to AgNPs than AgNO3. Further more, H2O2 has an ability to induce zebrafish oocytes maturation by induction of apoptosis in ovarian follicle cells. Taken together, the results from our study indicated that oxidative stress appeared to be one of important mechanisms in AgNP induced apoptosis in ovarian follicle cells, which further triggered the GVBD.

The Transcription Levels and Prognostic Values of Seven Proteasome Alpha Subunits in Human Cancers

Oncotarget. Jan, 2017  |  Pubmed ID: 27966459

Proteasome alpha subunits (PSMAs) have been shown to participate in the malignant progression of human cancers. However, the expression patterns and prognostic values of individual PSMAs remain elusive in most cancers. In the present study, we investigated the mRNA expression levels of seven PSMAs in different kinds of cancers using Oncomine and The Cancer Genome Atlas (TCGA) databases. The prognostic significance of PSMAs was also determined by Kaplan-Meier Plotter and PrognScan databases. Combined with Oncomine and TCGA, the mRNA expression levels of PSMA1-7 were significantly upregulated in breast, lung, gastric, bladder and head and neck cancer compared with normal tissues. Moreover, only PSMA6 and PSMA5 were not overexpressed in colorectal and kidney cancer, respectively. In survival analyses based on Kaplan-Meier Plotter, PSMA1-7 showed significant prognostic values in breast, lung and gastric cancer. Furthermore, potential correlations between PSMAs and survival outcomes were also observed in ovarian cancer, colorectal cancer and melanoma by Kaplan-Meier Plotter and PrognScan. These data indicated that PSMAs might serve as novel biomarkers and potential therapeutic targets for multiple human cancers. However, further studies are needed to explore the detailed biological functions and molecular mechanisms involved in tumor progression.

A Novel GLP-1 Analog, a Dimer of GLP-1 Via Covalent Linkage by a Lysine, Prolongs the Action of GLP-1 in the Treatment of Type 2 Diabetes

Peptides. Feb, 2017  |  Pubmed ID: 27965024

GLP-1 is an incretin hormone that can effectively lower blood glucose, however, the short time of biological activity and the side effect limit its therapeutic application. Many methods have been tried to optimize GLP-1 to extend its in vivo half-time, reduce its side effect and enhance its activity. Here we have chosen the idea to dimerize GLP-1 with a C-terminal lysine to form a new GLP-1 analog, DLG3312. We have explored the structure and the biological property of DLG3312, and the results indicated that DLG3312 not only remained the ability to activate the GLP-1R, but also strongly stimulated Min6 cell to secrete insulin. The in vivo bioactivities have been tested on two kinds of animal models, the STZ induced T2DM mice and the db/db mice, respectively. DLG3312 showed potent anti-diabetic ability in glucose tolerance assay and single-dose administration of DLG3312 could lower blood glucose for at least 10 hours. Long-term treatment with DLG3312 can reduce fasted blood glucose, decrease water consumption and food intake and significantly reduce the HbA1c level by 1.80% and 2.37% on STZ induced T2DM mice and the db/db mice, respectively. We also compared DLG3312 with liraglutide to investigate its integrated control of the type 2 diabetes. The results indicated that DLG3312 almost has the same effect as liraglutide but with a much simpler preparation process. In conclusion, we, by using C-terminal lysine as a linker, have synthesized a novel GLP-1 analog, DLG3312. With simplified preparation and improved physiological characterizations, DLG3312 could be considered as a promising candidate for the type 2 diabetes therapy.

Comparison of Soluble Urokinase Plasminogen Activator Receptor, Soluble Triggering Receptor Expressed on Myeloid Cells 1, Procalcitonin and C-reactive Protein in Distinguishing Concurrent Bacterial Infection from Idiopathic Inflammatory Myopathy

Rheumatology International. Apr, 2017  |  Pubmed ID: 27878344

The aim of the study was to measure the diagnostic values of biomarkers of bacterial infection in idiopathic inflammatory myopathy (IIM) patients. The serum and clinical data of 82 IIM patients with/without bacterial infection were collected. Concentrations of soluble urokinase plasminogen activator receptor (suPAR), soluble triggering receptor expressed on myeloid cells 1 (sTREM-1), procalcitonin (PCT) and C-reactive protein (CRP) were measured in IIM patients and healthy controls. There were no significant differences in serum suPAR and sTREM-1 levels between healthy controls and non-infection IIM patients. Serum levels of suPAR, sTREM-1, PCT and CRP measured in this study were significantly higher in the IIM patient group with concurrent infection than in the non-infection IIM patient group (p < 0.05). The biomarker suPAR showed the highest diagnostic value with sensitivity, specificity, positive predictive value and negative predictive value of 81.6, 77.3, 75.6 and 82.9%, respectively. Combining suPAR negative and CRP negative to rule out bacterial infection in IIM patients provides a very high specificity of 97.4%. Both suPAR and CRP positive to confirm bacterial infection give the specificity of 90.9%. The inflammatory biomarkers suPAR, sTREM-1, PCT and CRP offer diagnostic accuracy in detecting bacterial infection in IIM patients. Particularly, suPAR is the most sensitive and specific biomarker to predict bacterial infection in IIM patients. Combination of suPAR and CRP serum levels provides an even better confirmation of bacterial infection.

CHARMM36m: an Improved Force Field for Folded and Intrinsically Disordered Proteins

Nature Methods. Jan, 2017  |  Pubmed ID: 27819658

The all-atom additive CHARMM36 protein force field is widely used in molecular modeling and simulations. We present its refinement, CHARMM36m (, with improved accuracy in generating polypeptide backbone conformational ensembles for intrinsically disordered peptides and proteins.

A Potent Adjuvant Effect of a CD1d-binding NKT Cell Ligand in Human Immune System Mice

Expert Review of Vaccines. Jan, 2017  |  Pubmed ID: 27801602

A CD1d-binding invariant natural killer T (iNKT)-cell stimulatory glycolipid, namely 7DW8-5, is shown to enhance the efficacy of radiation-attenuated sporozoites (RAS)-based malaria vaccine in mice. In the current study, we aim to determine whether 7DW8-5 can display a potent adjuvant effect in human immune system (HIS) mice.

Changing Treatment May Affect the Predictive Ability of European Treatment Outcome Study Scoring for the Prognosis of Patients with Chronic Myeloid Leukemia

Turkish Journal of Haematology : Official Journal of Turkish Society of Haematology. Mar, 2017  |  Pubmed ID: 27751981

Previous studies compared the predictive ability of the European Treatment Outcome Study (EUTOS), Sokal, and Hasford scoring systems and demonstrated inconsistent findings with unknown reasons. This study was conducted to determine a useful scoring system to predict the prognosis of patients with chronic myeloid leukemia (CML) and identify the probable factors that affect the scoring.

Absolute Binding Free Energies for Octa-acids and Guests in SAMPL5 : Evaluating Binding Free Energies for Octa-acid and Guest Complexes in the SAMPL5 Blind Challenge

Journal of Computer-aided Molecular Design. Jan, 2017  |  Pubmed ID: 27696242

As part of the SAMPL5 blind prediction challenge, we calculate the absolute binding free energies of six guest molecules to an octa-acid (OAH) and to a methylated octa-acid (OAMe). We use the double decoupling method via thermodynamic integration (TI) or Hamiltonian replica exchange in connection with the Bennett acceptance ratio (HREM-BAR). We produce the binding poses either through manual docking or by using GalaxyDock-HG, a docking software developed specifically for this study. The root mean square deviations for our most accurate predictions are 1.4 kcal mol(-1) for OAH with TI and 1.9 kcal mol(-1) for OAMe with HREM-BAR. Our best results for OAMe were obtained for systems with ionic concentrations corresponding to the ionic strength of the experimental solution. The most problematic system contains a halogenated guest. Our attempt to model the σ-hole of the bromine using a constrained off-site point charge, does not improve results. We use results from molecular dynamics simulations to argue that the distinct binding affinities of this guest to OAH and OAMe are due to a difference in the flexibility of the host. We believe that the results of this extensive analysis of host-guest complexes will help improve the protocol used in predicting binding affinities for larger systems, such as protein-substrate compounds.

Absolute Binding Free Energy Calculations of CBClip Host-guest Systems in the SAMPL5 Blind Challenge

Journal of Computer-aided Molecular Design. Jan, 2017  |  Pubmed ID: 27677749

Herein, we report the absolute binding free energy calculations of CBClip complexes in the SAMPL5 blind challenge. Initial conformations of CBClip complexes were obtained using docking and molecular dynamics simulations. Free energy calculations were performed using thermodynamic integration (TI) with soft-core potentials and Bennett's acceptance ratio (BAR) method based on a serial insertion scheme. We compared the results obtained with TI simulations with soft-core potentials and Hamiltonian replica exchange simulations with the serial insertion method combined with the BAR method. The results show that the difference between the two methods can be mainly attributed to the van der Waals free energies, suggesting that either the simulations used for TI or the simulations used for BAR, or both are not fully converged and the two sets of simulations may have sampled difference phase space regions. The penalty scores of force field parameters of the 10 guest molecules provided by CHARMM Generalized Force Field can be an indicator of the accuracy of binding free energy calculations. Among our submissions, the combination of docking and TI performed best, which yielded the root mean square deviation of 2.94 kcal/mol and an average unsigned error of 3.41 kcal/mol for the ten guest molecules. These values were best overall among all participants. However, our submissions had little correlation with experiments.

Functional Brain Network Alterations in Clinically Isolated Syndrome and Multiple Sclerosis: A Graph-based Connectome Study

Radiology. Feb, 2017  |  Pubmed ID: 27541686

Purpose To investigate the topological organization of functional brain networks in clinically isolated syndrome (CIS) and multiple sclerosis (MS) and examine the clinical relevance. Materials and Methods The institutional review board of Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China, approved the study, and written informed consent was obtained from each participant. Functional brain networks were constructed for 34 patients with MS, 34 patients with CIS, and 36 matched healthy control subjects by using resting-state functional magnetic resonance (MR) imaging data. Graph-based network measures were then calculated, followed by performance of between-group comparison and brain-behavior correlation analysis. Results Decreased whole-brain network efficiency was observed for patients with MS when compared with healthy control subjects, with intermediate values for the patients with CIS (P < .05, corrected). Regionally, both patient groups showed decreased nodal efficiency in the left rolandic operculum and insula and the superior temporal gyrus of the bilateral temporal pole (P < .05, corrected). Moreover, impaired functional connectivity involving the occipital, temporal, and frontal cortices and the insula was identified in MS (P = .007), and a similar but smaller component was observed in CIS (P = .032). The disrupted functional connectivity correlated with disease duration of the patients (r = 0.312, P = .011) and served to distinguish the patients from healthy control subjects with high performance (area under the curve for MS, 0.825 [P < .001]; area under the curve for CIS, 0.789 [P < .001]). These findings were reproducible across several different analytical strategies and were largely independent of white matter lesions and gray matter atrophy. Conclusion The results of this study demonstrate that disrupted network organization already emerges in CIS, with a lesser degree relative to MS. (©) RSNA, 2016 Online supplemental material is available for this article.

Pogostone Induces Autophagy and Apoptosis Involving PI3K/Akt/mTOR Axis in Human Colorectal Carcinoma HCT116 Cells

Journal of Ethnopharmacology. Apr, 2017  |  Pubmed ID: 27416805

Pogostemon cablin is a medicinal herb widely used to treat gastrointestinal diseases in many Asian countries. Pogostone is an important constituent of Pogostemon cablin, and possesses various bioactivitys. In this study, we performed to investigate the anti-colorectal tumor property of Pogostone by inducing aurophagy and apoptosis in human colorectal cancer cells, and to define the potential molecular mechanisms.

Liver X Receptor β Is Involved in Formalin-Induced Spontaneous Pain

Molecular Neurobiology. Mar, 2017  |  Pubmed ID: 26846362

Increasing evidence indicates that the liver X receptor(LXR) β modulates inflammatory pain. However, the molecular mechanisms through which LXRβ modulates pain are unclear. Here, we found that LXRβ-null mice responded more strongly to acute noxious stimuli than wild-type (WT) littermates (in the hot plate and Hargreaves tests) and had augmented tonic inflammatory pain (in the formalin test). This increased reactivity to inflammatory pain was accompanied by enhanced formalin-evoked Fos and pERK staining of second-order nociceptive neurons. Immunohistochemistry showed that the expression of CGRP, SP, and IB4 was increased in the lamina I-II of the lumbar dorsal horns in formalin-injected LXRβ knockout (KO) mice compared with the WT controls. In addition, LXRβ deletion in the mice enhanced the formalin-induced inflammation with more activated microglia and astrocytes in the spinal cord. Furthermore, the levels of pro-inflammatory cytokines (IL-1β ,TNF-α) as well as NFκB in the formalin-injected paw were elevated by the loss of LXRβ. Taken together, these data indicate that LXRβ is involved in acute as well as inflammatory pain, and thus, it may be considered as a new target for the development of analgesics.

The Complete Mitochondrial Genome of the Royal Dottyback Pictichromis Paccagnellae (Perciformes: Pseudochromidae)

Mitochondrial DNA. Part A, DNA Mapping, Sequencing, and Analysis. Mar, 2017  |  Pubmed ID: 26713940

In this study, the complete mitogenome sequence of the Royal dottyback, Pictichromis paccagnellae (Perciformes: Pseudochromidae), has been sequenced by the next-generation sequencing method. The assembled mitogenome was of 16 976 bp in length, consisting of 13 protein-coding genes, 22 transfer RNAs, and two ribosomal RNAs genes. The overall base composition was 27.4% for A, 28.1% for C, 17.3% for G, and 27.2% for T and showed 76% identities to Fire-tail devil Labracinus cyclophthalmus in the same family. The complete mitogenome of P. paccagnellae provides essential and important DNA molecular data for further phylogeography and evolutionary analysis for Pseudochromidae.

The Complete Mitochondrial Genome of the Palette Surgeonfish, Paracanthurus Hepatus (Perciformes: Acanthuridae)

Mitochondrial DNA. Part A, DNA Mapping, Sequencing, and Analysis. Jan, 2017  |  Pubmed ID: 26652655

In this study, the complete mitogenome sequence of the palette surgeonfish, Paracanthurus hepatus (Perciformes: Acanthuridae), has been sequenced by next-generation sequencing method. The assembled mitogenome was 16 498 bp in length, consisted of 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs genes. The overall base composition of palette surgeonfish was 28.6% for A, 28.6% for C, 16.3% for G, 26.4% for T and showed 87% identities to somber surgeonfish Zebrasoma flavescens. The complete mitogenome of the palette surgeonfish provides essential and important DNA molecular data for further phylogeography and evolutionary analysis for surgeonfish's phylogeny.

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