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Other Publications (522)
- World Journal of Diabetes
- Journal of the American Chemical Society
- Chinese Medical Journal
- Nucleic Acids Research
- Angewandte Chemie (International Ed. in English)
- Parasites & Vectors
- Free Radical Biology & Medicine
- International Journal of Hematology
- Nanotechnology
- Physical Chemistry Chemical Physics : PCCP
- Wei Sheng Wu Xue Bao = Acta Microbiologica Sinica
- Hearing Research
- Endocrinology
- Zhonghua Shao Shang Za Zhi = Zhonghua Shaoshang Zazhi = Chinese Journal of Burns
- The Journal of Adhesive Dentistry
- Orthopedics
- American Journal of Infection Control
- Enzyme Research
- Heart and Vessels
- Biomacromolecules
- International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists
- Brain Research Bulletin
- PloS One
- Animal Reproduction Science
- Journal of Cranio-maxillo-facial Surgery : Official Publication of the European Association for Cranio-Maxillo-Facial Surgery
- Respiratory Medicine
- Systems Biology in Reproductive Medicine
- Journal of Bioscience and Bioengineering
- FEMS Microbiology Ecology
- The Journal of Organic Chemistry
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Journal of the American Chemical Society
- Biomaterials
- Optics Letters
- ChemSusChem
- Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology
- BMC Systems Biology
- BMC Systems Biology
- IEEE Transactions on Neural Networks / a Publication of the IEEE Neural Networks Council
- Molecules (Basel, Switzerland)
- Plant Cell Reports
- Journal of Cardiovascular Pharmacology
- Nanoscale Research Letters
- Nature Protocols
- FEBS Letters
- Journal of Bacteriology
- Optics Express
- Acta Crystallographica. Section E, Structure Reports Online
- Chemistry & Biodiversity
- Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)
- The Chinese Journal of Physiology
- Journal of Zhejiang University. Science. B
- BMC Bioinformatics
- PloS One
- Journal of Virology
- Organic Letters
- Nature Genetics
- The Analyst
- Acta Crystallographica. Section E, Structure Reports Online
- Acta Crystallographica. Section E, Structure Reports Online
- Journal of Pediatric Surgery
- Journal of Thrombosis and Thrombolysis
- Biomedical Microdevices
- ACS Nano
- Burns : Journal of the International Society for Burn Injuries
- Inorganic Chemistry
- Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University
- Journal of Clinical Psychopharmacology
- Zhongguo Gu Shang = China Journal of Orthopaedics and Traumatology
- Journal of Insect Science (Online)
- Biochemical and Biophysical Research Communications
- Evidence-based Complementary and Alternative Medicine : ECAM
- Nanoscale
- Science Translational Medicine
- Biomaterials
- The Journal of Biological Chemistry
- Nature Nanotechnology
- Physical Chemistry Chemical Physics : PCCP
- International Journal of Clinical and Experimental Pathology
- Journal of Molecular Modeling
- Zhonghua Wai Ke Za Zhi [Chinese Journal of Surgery]
- ChemSusChem
- Journal of Chromatography. A
- Genetics and Molecular Biology
- Journal of Computer-aided Molecular Design
- Chinese Medical Journal
- Chinese Medical Journal
- Dental Materials : Official Publication of the Academy of Dental Materials
- ACS Nano
- Science (New York, N.Y.)
- ACS Nano
- BMC Cancer
- Journal of Athletic Training
- Heart (British Cardiac Society)
- Nanoscale
- Thrombosis Research
- Journal of Vascular and Interventional Radiology : JVIR
- Acta Pharmacologica Sinica
- European Journal of Lipid Science and Technology : EJLST
- Journal of Radiation Research
- Growth Factors (Chur, Switzerland)
- Transgenic Research
- World Neurosurgery
- World Journal of Gastroenterology : WJG
- Archives of Oral Biology
- PloS One
- Fungal Genetics and Biology : FG & B
- The Tohoku Journal of Experimental Medicine
- The Journal of Biological Chemistry
- Radiation Research
- Cancer Cell
- Journal of the American College of Cardiology
- Nanotechnology
- BMC Bioinformatics
- Vaccine
- Molecules (Basel, Switzerland)
- Biotechnology Journal
- Chinese Medical Journal
- Chinese Medical Journal
- Journal of the American Chemical Society
- Zhonghua Yi Xue Za Zhi
- Journal of Child Neurology
- PloS One
- Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi = Chinese Journal of Integrated Traditional and Western Medicine / Zhongguo Zhong Xi Yi Jie He Xue Hui, Zhongguo Zhong Yi Yan Jiu Yuan Zhu Ban
- Computational Biology and Chemistry
- Journal of Materials Science. Materials in Medicine
- Nano Reviews
- Small (Weinheim an Der Bergstrasse, Germany)
- Molecular Reproduction and Development
- PloS One
- The Chinese Journal of Physiology
- Optics Letters
- PloS One
- Medical Gas Research
- Nanoscale Research Letters
- Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics
- Phytotherapy Research : PTR
- Viruses
- Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi = Chinese Journal of Schistosomiasis Control
- Brain : a Journal of Neurology
- PloS One
- Parasitology Research
- Journal of Controlled Release : Official Journal of the Controlled Release Society
- Journal of Controlled Release : Official Journal of the Controlled Release Society
- Acta Crystallographica. Section E, Structure Reports Online
- Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University
- PloS One
- International Journal of Nanomedicine
- Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference
- International Forum of Allergy & Rhinology
- General Dentistry
- Zhonghua Yi Xue Za Zhi
- Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Chinese Journal of Otorhinolaryngology Head and Neck Surgery
- Molecular Biology Reports
- IEEE Transactions on Systems, Man, and Cybernetics. Part B, Cybernetics : a Publication of the IEEE Systems, Man, and Cybernetics Society
- Molecular and Cellular Biochemistry
- Proteins
- Molecular Medicine Reports
- International Journal of Oncology
- Journal of Dentistry
- Physical Chemistry Chemical Physics : PCCP
- Dental Materials : Official Publication of the Academy of Dental Materials
- Pest Management Science
- Biomaterials
- Foodborne Pathogens and Disease
- Molecular Reproduction and Development
- Angewandte Chemie (International Ed. in English)
- Pharmacological Research : the Official Journal of the Italian Pharmacological Society
- Nature Genetics
- ACS Nano
- Analytical Chemistry
- Plant Physiology and Biochemistry : PPB / Société Française De Physiologie Végétale
- Organic & Biomolecular Chemistry
- Brain Research
- Langmuir : the ACS Journal of Surfaces and Colloids
- Molecular Ecology
- Chemical Communications (Cambridge, England)
- Biomedical Microdevices
- BMC Neuroscience
- Annals of Hematology
- Clinical Cardiology
- The American Journal of Cardiology
- Biochemical Genetics
- The Journal of Adhesive Dentistry
- The FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
- Organic Letters
- PloS One
- Analytical Chemistry
- Acta Pharmacologica Sinica
- Ultrasound in Medicine & Biology
- International Journal of Cardiology
- Asian Pacific Journal of Tropical Medicine
- Chemical Communications (Cambridge, England)
- Nano Letters
- Nano Letters
- Vaccine
- Molecular Biology Reports
- Chemical Communications (Cambridge, England)
- Angewandte Chemie (International Ed. in English)
- Journal of Materials Science
- Journal of Proteome Research
- Neuropharmacology
- Clinical & Experimental Metastasis
- PloS One
- Current Eye Research
- European Journal of Oral Sciences
- Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics
- International Journal of Biological Macromolecules
- Inflammation
- Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine]
- Therapeutic Advances in Musculoskeletal Disease
- Neurology India
- BMJ (Clinical Research Ed.)
- Evidence-based Complementary and Alternative Medicine : ECAM
- Applied Microbiology and Biotechnology
- The International Journal of Oral & Maxillofacial Implants
- Pharmaceutical Development and Technology
- Obesity Surgery
- PloS One
- Chinese Medical Journal
- Zhonghua Xin Xue Guan Bing Za Zhi
- Scientific Reports
- Physical Review Letters
- Journal of Structural Biology
- PloS One
- Journal of Virological Methods
- Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban
- Chemical Communications (Cambridge, England)
- Cell Cycle (Georgetown, Tex.)
- International Journal of Oral Science
- Materials Science & Engineering. C, Materials for Biological Applications
- Molecular Medicine Reports
- Chemistry Central Journal
- Journal of Fluids Engineering
- Current Diabetes Reports
- Chemical Communications (Cambridge, England)
- Animal Biotechnology
- World Neurosurgery
- PloS One
- International Journal of Cardiology
- Arthritis Research & Therapy
- Advanced Materials (Deerfield Beach, Fla.)
- Langmuir : the ACS Journal of Surfaces and Colloids
- Journal of the American Academy of Dermatology
- Archives of Virology
- PloS One
- PloS One
- Genome Biology
- Molecular and Cellular Biochemistry
- International Journal of Nanomedicine
- Human Reproduction (Oxford, England)
- Zhongguo Zhong Xi Yi Jie He Za Zhi Zhongguo Zhongxiyi Jiehe Zazhi = Chinese Journal of Integrated Traditional and Western Medicine / Zhongguo Zhong Xi Yi Jie He Xue Hui, Zhongguo Zhong Yi Yan Jiu Yuan Zhu Ban
- Chinese Medical Journal
- Medical Science Monitor Basic Research
- Journal of Microbiology (Seoul, Korea)
- Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi Kouqiang Yixue Zazhi = West China Journal of Stomatology
- Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology
- Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
- Journal of Physics. Condensed Matter : an Institute of Physics Journal
- Zhonghua Kou Qiang Yi Xue Za Zhi = Zhonghua Kouqiang Yixue Zazhi = Chinese Journal of Stomatology
- Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
- Chemistry (Weinheim an Der Bergstrasse, Germany)
- Zhongguo Yi Liao Qi Xie Za Zhi = Chinese Journal of Medical Instrumentation
- Organic Letters
- Chemical Communications (Cambridge, England)
- Nano Letters
- Nanomedicine : Nanotechnology, Biology, and Medicine
- Gastroenterology
- The Journal of Craniofacial Surgery
- PloS One
- Quantitative Imaging in Medicine and Surgery
- Proceedings of the National Academy of Sciences of the United States of America
- Marine Drugs
- Journal of Agricultural and Food Chemistry
- Archives of Medical Research
- Neurosurgery
- Molecular Biology Reports
- Journal of the American Chemical Society
- Zhonghua Wei Chang Wai Ke Za Zhi = Chinese Journal of Gastrointestinal Surgery
- Se Pu = Chinese Journal of Chromatography / Zhongguo Hua Xue Hui
- Nature Communications
- PloS One
- IET Systems Biology
- Cell Transplantation
- Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica
- ACS Nano
- DNA and Cell Biology
- Analytical Chemistry
- Nano Letters
- The Journal of Organic Chemistry
- Scientific Reports
- The FEBS Journal
- Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
- Molecular BioSystems
- Langmuir : the ACS Journal of Surfaces and Colloids
- PloS One
- Experimental Lung Research
- Zhonghua Kou Qiang Yi Xue Za Zhi = Zhonghua Kouqiang Yixue Zazhi = Chinese Journal of Stomatology
- Physical Chemistry Chemical Physics : PCCP
- Bioorganic & Medicinal Chemistry
- Clinical Neurology and Neurosurgery
- PloS One
- ACS Nano
- Water Science and Technology : a Journal of the International Association on Water Pollution Research
- International Journal of Environmental Research and Public Health
- Scientific Reports
- Lancet
- Molecular and Cellular Endocrinology
- PloS One
- Integrative Zoology
- Micron (Oxford, England : 1993)
- ACS Applied Materials & Interfaces
- Scientific Reports
- The American Surgeon
- PloS One
- Hippocampus
- Oncology Letters
- Drug Design, Development and Therapy
- PloS One
- Scientific Reports
- Molecular and Cellular Endocrinology
- Biomedical and Environmental Sciences : BES
- BMC Systems Biology
- BMC Systems Biology
- Bio-medical Materials and Engineering
- PloS One
- PloS One
- Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences
- Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences
- Journal of the Neurological Sciences
- ELife
- BMC Complementary and Alternative Medicine
- Asian Pacific Journal of Cancer Prevention : APJCP
- Obesity Surgery
- Frontiers in Microbiology
- Cellular Signalling
- BMC Infectious Diseases
- FEMS Microbiology Ecology
- Bone
- PloS One
- PloS One
- The International Journal of Prosthodontics
- Synapse (New York, N.Y.)
- Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi
- International Journal of Cancer. Journal International Du Cancer
- Clinical Chemistry and Laboratory Medicine : CCLM / FESCC
- PloS One
- Blood
- Angewandte Chemie (International Ed. in English)
- Toxicology Letters
- Biomaterials
- Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
- Vascular and Endovascular Surgery
- Planta
- ChemSusChem
- ACS Nano
- Biotechnology Letters
- Parasitology Research
- Endocrine Research
- International Journal of Cardiology
- Dalton Transactions (Cambridge, England : 2003)
- Dalton Transactions (Cambridge, England : 2003)
- MBio
- Organic Letters
- Cancer Genetics
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Nanoscale Research Letters
- Neuroreport
- Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
- IEEE Transactions on Cybernetics
- Journal of Chromatography. A
- World Journal of Surgical Oncology
- International Journal for Parasitology
- Zhonghua Kou Qiang Yi Xue Za Zhi = Zhonghua Kouqiang Yixue Zazhi = Chinese Journal of Stomatology
- PloS One
- Heart and Vessels
- Cellular Reprogramming
- International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases
- International Journal of Cardiology
- Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
- Acta Neurochirurgica
- Reproductive Biology and Endocrinology : RB&E
- Biological Trace Element Research
- ChemSusChem
- Journal of Nanoscience and Nanotechnology
- Microbial Ecology
- PloS One
- The British Journal of Psychiatry : the Journal of Mental Science
- International Journal of Cardiology
- Chemistry, an Asian Journal
- Se Pu = Chinese Journal of Chromatography / Zhongguo Hua Xue Hui
- The European Respiratory Journal
- Nano Letters
- Chemical Society Reviews
- International Heart Journal
- Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
- Nature Nanotechnology
- NMR in Biomedicine
- Chemical Communications (Cambridge, England)
- Evidence-based Complementary and Alternative Medicine : ECAM
- Sheng Wu Gong Cheng Xue Bao = Chinese Journal of Biotechnology
- Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
- PloS One
- International Journal of Urology : Official Journal of the Japanese Urological Association
- Journal of Clinical Microbiology
- Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban
- Journal of the Science of Food and Agriculture
- Talanta
- Nano Letters
- Zhonghua Yi Xue Za Zhi
- Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases
- Cryobiology
- Journal of Dentistry
- Epileptic Disorders : International Epilepsy Journal with Videotape
- Acta Biologica Hungarica
- BioMed Research International
- Proceedings of the National Academy of Sciences of the United States of America
- International Immunopharmacology
- Wilderness & Environmental Medicine
- BMC Medical Genetics
- Lasers in Medical Science
- Chemical Biology & Drug Design
- Molecular Medicine Reports
- Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
- Neurochemical Research
- ACS Nano
- Journal of Clinical Microbiology
- BioMed Research International
- BMC Psychiatry
- Science China. Life Sciences
- Journal of the Science of Food and Agriculture
- Frontiers in Pediatrics
- Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
- Nanoscale
- Biochemical and Biophysical Research Communications
- PloS One
- Cell Biochemistry and Biophysics
- Chemical Communications (Cambridge, England)
- PloS One
- Biomaterials
- Oncology Letters
- PloS One
- International Journal of Clinical and Experimental Pathology
- Romanian Journal of Morphology and Embryology = Revue Roumaine De Morphologie Et Embryologie
- Bioinformatics (Oxford, England)
- Die Pharmazie
- Journal of Neuroscience Research
- PLoS Computational Biology
- Obesity Surgery
- Journal of the Neurological Sciences
- American Journal of Dentistry
- ACS Applied Materials & Interfaces
- Analytical Chemistry
- TheScientificWorldJournal
- COPD
- Veterinary Journal (London, England : 1997)
- BMC Complementary and Alternative Medicine
- Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
- Food & Function
- NeuroImage
- PloS One
- Acta Diabetologica
- Genome Announcements
- The Analyst
- Asian-Australasian Journal of Animal Sciences
- Zhonghua Wei Chang Wai Ke Za Zhi = Chinese Journal of Gastrointestinal Surgery
- Die Pharmazie
- Organic Letters
- Nature
- Angewandte Chemie (International Ed. in English)
- Medical Oncology (Northwood, London, England)
- Environmental Microbiology
- Mitochondrial DNA
- FEMS Microbiology Letters
- The Journal of the Acoustical Society of America
- IEEE Transactions on Cybernetics
- Scientific Reports
- Nano Letters
- Scientific Reports
- International Orthopaedics
- European Journal of Nuclear Medicine and Molecular Imaging
- Inflammation
- Genetic Testing and Molecular Biomarkers
- Medical Oncology (Northwood, London, England)
- PloS One
- PLoS Pathogens
- Journal of Hazardous Materials
- Chinese Medical Journal
- Cellular and Molecular Neurobiology
- Nanoscale Research Letters
- International Journal of Endocrinology
- IEEE Transactions on Cybernetics
- Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
- PloS One
- Nanoscale
- Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
- TheScientificWorldJournal
- Chemical Communications (Cambridge, England)
- Connective Tissue Research
- Nano Letters
- Zhonghua Xin Xue Guan Bing Za Zhi
- Dalton Transactions (Cambridge, England : 2003)
- Journal of Cardiovascular Pharmacology
- Science (New York, N.Y.)
- Biomaterials
- Nanoscale
- PLoS Computational Biology
- Biosensors & Bioelectronics
- TheScientificWorldJournal
- Chemical Communications (Cambridge, England)
- Chemical Communications (Cambridge, England)
- Zhonghua Kou Qiang Yi Xue Za Zhi = Zhonghua Kouqiang Yixue Zazhi = Chinese Journal of Stomatology
- PloS One
- Lasers in Medical Science
- Scientific Reports
- Tuberculosis (Edinburgh, Scotland)
- Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
- Transgenic Research
- Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi = Chinese Journal of Otorhinolaryngology Head and Neck Surgery
- Bioorganic & Medicinal Chemistry Letters
- Journal of Affective Disorders
- Food Chemistry
Articles by Yong Wang in JoVE
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En Multi-parametriska Islet Perifusion System inom en mikroflödessystem Perifusion enhet
Adeola F. Adewola1, Yong Wang1, Tricia Harvat1, David T. Eddington2, Dongyoung Lee1, Jose Oberholzer1,2
1Department of Surgery, University of Illinois, Chicago, 2Department of Bioengineering, University of Illinois, Chicago
En mikroflödessystem holme perifusion enhet har utvecklats för bedömning av dynamiska insulinsekretionen av flera holmar och samtidiga fluorescens avbildning av kalciuminflödet och mitokondrie eventuella förändringar.
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Kvantitativ och Temporal Kontroll av syremikromiljö vid den inre Islet nivå
Joe Fu-Jiou Lo1, Yong Wang2,3, Zidong Li1, Zhengtuo Zhao1, Di Hu1, David T. Eddington3, Jose Oberholzer2,3
1Department of Mechanical Engineering, University of Michigan-Dearborn, 2Department of Surgery/Transplant, University of Illinois at Chicago, 3Department of Bioengineering, University of Illinois at Chicago
Mikroflödessyrekontroll ger mer än bara bekvämlighet och hastighet över hypoxiska kammare för biologiska experiment. Speciellt när förs via diffusion genom ett membran, kan mikroflödes syre ger samtidig vätska och gasfas modulationer på mikronivå. Denna teknik möjliggör dynamiska fler parametriska experiment kritiska för att studera holme patofysiologi.
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Fluorescens Imaging med One-nanometer Noggrannhet (FIONA)
Yong Wang*1,2, En Cai*1,2, Janet Sheung1,2, Sang Hak Lee1,2, Kai Wen Teng2,3, Paul R. Selvin1,2,3
1Department of Physics, University of Illinois at Urbana-Champaign, 2Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, 3Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign
Enstaka fluoroforer kan lokaliseras med nanometerprecision med hjälp FIONA. Här en sammanfattning av den FIONA teknik rapporteras, och hur man utför FIONA experiment beskrivs.
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Other articles by Yong Wang on PubMed
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Reactive Oxygen Species and Hematopoietic Stem Cell Senescence
International Journal of Hematology.
Jul, 2011 |
Pubmed ID: 21567162 Hematopoietic stem cells (HSCs) are responsible for sustaining hematopoietic homeostasis and regeneration after injury for the entire lifespan of an organism through self-renewal, proliferation, differentiation, and mobilization. Their functions can be affected by reactive oxygen species (ROS) that are produced endogenously through cellular metabolism or after exposure to exogenous stress. At physiological levels, ROS function as signal molecules which can regulate a variety of cellular functions, including HSC proliferation, differentiation, and mobilization. However, an abnormal increase in ROS production occurs under various pathological conditions, which can inhibit HSC self-renewal and induce HSC senescence, resulting in premature exhaustion of HSCs and hematopoietic dysfunction. This review aims to provide a summary of a number of recent findings regarding the cellular sources of ROS in HSCs and the mechanisms of action whereby ROS induce HSC senescence. In particular, we highlight the roles of the p38 mitogen-activated protein kinase (p38)-p16(Ink4a) (p16) pathway in mediating ROS-induced HSC senescence.
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Short-term Plasticity and Auditory Processing in the Ventral Cochlear Nucleus of Normal and Hearing-impaired Animals
Hearing Research.
Sep, 2011 |
Pubmed ID: 21586317 The dynamics of synaptic transmission between neurons plays a major role in neural information processing. In the cochlear nucleus, auditory nerve synapses have a relatively high release probability and show pronounced synaptic depression that, in conjunction with the variability of interspike intervals, shapes the information transmitted to the postsynaptic cells. Cellular mechanisms have been best analyzed at the endbulb synapses, revealing that the recent history of presynaptic activity plays a complex, non-linear, role in regulating release. Emerging evidence suggests that the dynamics of synaptic function differs according to the target neuron within the cochlear nucleus. One consequence of hearing loss is changes in evoked release at surviving auditory nerve synapses, and in some situations spontaneous release is greatly enhanced. In contrast, even with cochlear ablation, postsynaptic excitability is less affected. The existing evidence suggests that different modes of hearing loss can result in different dynamic patterns of synaptic transmission between the auditory nerve and postsynaptic neurons. These changes in dynamics in turn will affect the efficacy with which different kinds of information about the acoustic environment can be processed by the parallel pathways in the cochlear nucleus.
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Steroidogenic Factor-1 is Required for TGF-beta3-mediated 17beta-estradiol Synthesis in Mouse Ovarian Granulosa Cells
Endocrinology.
Aug, 2011 |
Pubmed ID: 21586554 The TGF-β superfamily members are indicated to play key roles in ovarian follicular development, such as granulosa cell proliferation, estrogens, and progesterone production. However, little is known about the roles of TGF-β3 in follicular development. In this study, we found that TGF-β3 was predominantly expressed in granulosa cells of mouse ovarian follicles, and it significantly promoted 17β-estradiol (E(2)) release in a dose-dependent manner. The orphan nuclear receptor steroidogenic factor-1 (SF-1) was required in TGF-β3-induced Cyp19a1 (a key rate-limiting enzyme for estrogen biosynthesis) expression and E(2) release. Additionally, TGF-β3 enhanced the binding of SF-1 to endogenous ovary-specific Cyp19a1 type II promoter, as evidenced by chromatin immunoprecipitation assays. The enhanced effect of SF-1 by TGF-β3 may be mediated through functional interactions between SF-1 and mothers against decapentaplegic homolog (Smad)3 (a mediator of TGF-β signaling pathway), because disruption of the interaction abolished the synergistic effects of SF-1, Smad3, and TGF-β3 on Cyp19a1 mRNA expression. RNA interference and chromatin immunoprecipitation studies also demonstrated that Smad3 was required for SF-1 binding to Cyp19a1 type II promoter and activation of Cyp19a1. Smad3 thus acts as a point of convergence that involves integration of SF-1 and TGF-β signaling in affecting E(2) production. Taken together, our data provide mechanistic insights into the roles of SF-1 in TGF-β3-mediated E(2) synthesis. Understanding of potential cross-points between extracellular signals affecting estrogen production will help to discover new therapeutic targets in estrogen-related diseases.
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Collagen Cross Linking Increases Its Biodegradation Resistance in Wet Dentin Bonding
The Journal of Adhesive Dentistry.
May, 2011 |
Pubmed ID: 21594232 Purpose: The biodegradation of exposed dentin collagen within the adhesive/dentin (a/d) interface is one of the main reasons for composite restoration failures and seriously affects the durability of dental restorations. In the present study, the objective was to investigate whether the inclusion of the cross-linking reagent (glutaraldehyde, GA) in the adhesive would increase collagen biodegradation resistance within the a/d interface. Materials and Methods: The model adhesive consisted of ~60 % monomers (HEMA/bis-GMA, 45/55 wt/wt) and ~ 40 % ethanol as a solvent. 5% GA was added to the above formulation. After the dentin surfaces were etched for 15 s with 35% phosphoric acid, rinsed with water and blotted dry, adhesives both with and without GA were applied and polymerized by visible light for 20 s. These a/d specimens were immersed in the biodegradation solution (prepared by adding 160 mg collagenase in 1 liter of TESCA buffer solution) for up to 30 days after proceeding with the sectioning/fracture to expose the a/d interfaces. The specimens were analyzed using SEM and micro-Raman spectroscopy. Results: SEM results indicated that for the adhesive without GA, there were many voids and a loss of collagen fibrils in the a/d interface after being challenged by the biodegradation solution. The Raman spectra collected from the interface showed that the amide I of collagen at 1667 cm-1 obviously decreased, indicating a removal of collagen fibrils during the degradation process. For the adhesive containing GA, the collagen fibrils within the interface did not degrade at all, which was also confirmed by the Raman results. Conclusion: The results corroborate the previous findings that by using the current adhesive system and wet bonding, the collagen fibrils in the a/d interface are largely unprotected and easily undergo biodegradation. Directly including cross-linking agents in the adhesive could protect collagen fibrils from degradation in situ within the a/d interface.
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Surgical Treatment and Prognosis of Acetabular Fractures Associated with Ipsilateral Femoral Neck Fractures
Orthopedics.
May, 2011 |
Pubmed ID: 21598880 Combined ipsilateral acetabular and femoral neck fractures are the result of high-energy trauma. Satisfactory treatment for this injury pattern remains a challenge, since traditional open reduction and internal fixation (ORIF) is always accompanied by a high prevalence of posttraumatic arthritis and avascular necrosis of the femoral head. Eight of 502 acetabular fractures from 1990 to 2008 were diagnosed with combined ipsilateral femoral neck fracture, in which 5 patients' fractures were associated with hip dislocation. These patients were injured from falls, traffic accidents, or crushing accidents. Radiographs and computed tomography scans were taken to check acetabular and femoral neck fractures. All of the patients underwent surgery using appropriate approaches and techniques. Postoperative radiographs demonstrated anatomic or satisfactory reduction for acetabular fractures as well as excellent or good reduction for femoral neck fractures in all of the patients. Follow-up radiographs showed femoral head necrosis in the 5 patients with femoral head dislocations, but not in the other 3 patients. We have seen few patients with this injury pattern, which makes us unable to detect significant differences between the patients associated with femoral head dislocation and those without femoral head dislocation. But by considering the results of our study and those reported in the literature, we believe that for patients with ipsilateral acetabular and femoral neck fractures without hip dislocation, satisfactory results could be expected after ORIF. But for those cases associated with hip dislocation, alternative methods such as acute THR as primary treatment are worthy of consideration.
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Transcatheter Closure of Perimembranous Ventricular Septal Defects (VSD) with VSD Occluder: Early and Mid-term Results
Heart and Vessels.
May, 2011 |
Pubmed ID: 21618026 Results of perimembranous ventricular septal defects (pmVSD) transcatheter closure have been reported in the literature, mostly with the Amplatzer VSD device (muscular or eccentric) (AGA Medical Corp., Golden Valley, MN, USA). However, the data of percutaneous closure of pmVSD with VSD occluder (VSD-O) made in China are still limited. We sought to analyze the safety, efficacy, and follow-up results of percutaneous closure of pmVSD with VSD-O made in China. Seventy-eight patients underwent percutaneous closure of pmVSD at our institution between February 2005 and June 2007. A VSD device made in china (Huayishengjie Medical Corp., Beijing, China) was used in all subjects. The mean age at closure was 11 years (range 2.5-44 years). The attempt to place the device was successful in 74 patients (94.9%). The median device size used was 8 mm (range 5-16 mm). No deaths occurred. Total occlusion rate was 62.8% at completion of the procedure, rising to 87.2% at discharge and 99% during the follow-up. A total of eight early complications occurred (10.3%), but in all subjects these were transient. The median follow-up was 32 months. The most significant complication was complete atrioventricular block (cAVB) in the early phase (five subjects, 6.4%) and during the follow-up (one subject, 1.3%), and there was no need for pacemaker implantation in six subjects. Logistic regression analysis showed that the only variable significantly associated with the occurrence of this complication was age at the time of the procedure (p = 0.025; OR 0.22). All subjects experiencing this problem were
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Clinicopathologic Correlations Between Human Papillomavirus 16 Infection and Beclin 1 Expression in Human Cervical Cancer
International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists.
Jul, 2011 |
Pubmed ID: 21623196 Our earlier study showed that the autophagy gene Beclin 1 could affect cell proliferation in a cervical cancer HeLa cell line. In this study, we examined Beclin 1 protein expression in 81 specimens of cervical squamous carcinoma by immunohistochemistry. Meanwhile, we detected E6 and E7 genes of human papillomavirus 16 in these tissues by polymerase chain reaction. Beclin 1 expression significantly decreased in samples of malignant cervical cancer tissues than in those of normal or cervical intraepithelial neoplasia tissues. The expression of Beclin 1 was associated with pelvic lymph node metastasis and histological grade, but did not correlate with International Federation of Gynecology and Obstetrics stage, age, depth of cervical infiltration, tumor size, and gross type of cervical lesion. The expression of Beclin 1 was not obviously correlated with E6 and E7 genes statistically. Therefore, decreased expression of Beclin 1 may be related to tumorigenesis and the development of cervical cancer, but is not significantly relevant with human papillomavirus 16 infection.
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Alterations of Emotion, Cognition and Firing Activity of the Basolateral Nucleus of the Amygdala After Partial Bilateral Lesions of the Nigrostriatal Pathway in Rats
Brain Research Bulletin.
Jul, 2011 |
Pubmed ID: 21624440 Although increasing evidence indicates that psychiatric symptoms are crucial characteristic of the early stage of Parkinson's disease (PD) and precede motor impairments, the neuronal firing activity of the basolateral nucleus of the amygdala (BLA) in the psychiatric symptom of PD and the involved mechanism are still unclear. In the present study, we examined the changes in emotional and cognitive tests not focused on motor fluency and firing activity of projection neurons in the BLA rats with 6-hydroxydopamine (6-OHDA) injected bilaterally into dorsal striatum, and the effects of apomorphine and the medial prefrontal cortex (mPFC) on these changes. Injection of 6-OHDA (10.5 μg) into the dorsal striatum produced 18-22% and 26-30% loss of tyrosine hydroxylase immunoreactive neurons in the ventral tegmental area and substantia nigra pars compacta of rats, respectively. The striatal lesions induced anxiety-like responses in the rats but did not result in depressive-like behavior or cognitive impairments. In the lesioned rats, the firing rate of BLA projection neurons decreased significantly compared with sham-operated rats, and the firing pattern of BLA projection neurons was not changed. No significant differences were observed either in behaviors or firing activity of BLA projection neurons by further ibotenic acid lesions of the mPFC in the lesioned rats. Systemic administration of cumulative apomorphine (10-160 μg/kg) inhibited the firing rate of BLA projection neurons in sham-operated, 6-OHDA-lesioned and combined 6-OHDA- and mPFC-lesioned rats, but the latter needed more apomorphine stimulation. These data suggest that the anxiety in early stage of PD is possibly related to the decrease in firing activity of BLA projection neurons, which may be regulated by the activation of dopamine receptor in the mPFC.
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Effects of Obstructive Sleep Apnea and Its Treatment on Cardiovascular Risk in CAD Patients
Respiratory Medicine.
Oct, 2011 |
Pubmed ID: 21646006 This study, in optimally treated CAD patients with newly diagnosed OSA, focused on (1) The relationships between OSA and serum biomarkers of four potential pathways of cardiovascular injury in OSA: high-sensitivity C-reactive protein (hs-CRP), endothelin-1 (ET-1), N terminal pro B type natriuretic peptide (NT-proBNP) and fibrinogen; and (2) The effect of continuous positive airway pressure (CPAP) therapy on these markers. 151 Chinese patients with proven CAD and standard medication were enrolled. After polysomnography, patients were classified into four groups according to apnea-hypopnea index (AHI): no OSA (n = 25); mild OSA (n = 50); moderate OSA (n = 43); severe OSA (n = 33). Morning levels of hs-CRP, ET-1, NT-proBNP and fibrinogen were assayed and repeated in severe OSA patients after 3-months CPAP treatment. Hs-CRP was greater in patients with severe OSA than those with no OSA or mild OSA (P = 0.001, P = 0.003; respectively). After adjustment for confounders, the hs-CRP levels correlated most strongly with AHI and oxygen desturation index (ODI) (r = 0.439, PÂ
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Antioxidant Treatment with Quercetin Ameliorates Erectile Dysfunction in Streptozotocin-induced Diabetic Rats
Journal of Bioscience and Bioengineering.
Sep, 2011 |
Pubmed ID: 21664865 Oxidative stress is demonstrated to be involved in the pathophysiological mechanism of erectile dysfunction (ED). Quercetin, a potent bioflavonoid, has been reported to have the antioxidant role. In the present study, we examined the effect of quercetin on ED and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Sprague-Dawley rats with a single intravenous injection of STZ. The diabetic rats were then randomized to diabetic group and quercetin therapy groups which were treated with quercetin at different doses of 5, 20 and 50mg/kg per day respectively. At the end of the 8th week, erectile function was assessed by measuring the rise in intracavernous pressure (ICP) following cavernous nerve electrostimulation. Superoxide dismutase (SOD) activity, thiobarbituric acid-reacting substance (TBARS) and nitrite and nitrate (NOx) levels were measured in cavernosum tissue. Endothelial NO synthase (eNOS) expression was determined using Western blot method. ICP in diabetic rats was significantly decreased than that in controls. After treatment with quercetin at the doses of 20 and 50mg/kg, ICP was significantly increased compared to that in untreated diabetic rats. Decreased levels of SOD activity, NOx and eNOS expression, as well as elevated levels of TBARS were found in diabetic group compared with control group. Treatment with 20 and 50mg/kg quercetin improved SOD activity, NOx and TBARS levels in corpus cavernosum of diabetic rats. Decreased expression of eNOS in diabetic rats was only ameliorated by 50mg/kg quercetin treatment. Quercetin could ameliorate ED in diabetic rats by inhibiting oxidative stress.
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Spectral Clustering on Multiple Manifolds
IEEE Transactions on Neural Networks / a Publication of the IEEE Neural Networks Council.
Jul, 2011 |
Pubmed ID: 21690009 Spectral clustering (SC) is a large family of grouping methods that partition data using eigenvectors of an affinity matrix derived from the data. Though SC methods have been successfully applied to a large number of challenging clustering scenarios, it is noteworthy that they will fail when there are significant intersections among different clusters. In this paper, based on the analysis that SC methods are able to work well when the affinity values of the points belonging to different clusters are relatively low, we propose a new method, called spectral multi-manifold clustering (SMMC), which is able to handle intersections. In our model, the data are assumed to lie on or close to multiple smooth low-dimensional manifolds, where some data manifolds are separated but some are intersecting. Then, local geometric information of the sampled data is incorporated to construct a suitable affinity matrix. Finally, spectral method is applied to this affinity matrix to group the data. Extensive experiments on synthetic as well as real datasets demonstrate the promising performance of SMMC.
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Proteomic Study on Sodium Selenite-induced Apoptosis of Human Cervical Cancer HeLa Cells
Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS).
Jul, 2011 |
Pubmed ID: 21767938 Sodium selenite can induce the apoptosis of cancer cells, however its mechanism has seldom been studied via proteomics. In this paper, human cervical cancer HeLa cells were investigated by MTT assay and morphological observation to get appropriate selenite concentrations for proteomic study. Results showed that selenite at concentrations larger than 10 μmol/L significantly inhibited the viability of HeLa cells. 40 μmol/L selenite was in the appropriate range for proteomic study. After 24 h treatment with 40 μmol/L selenite, total proteins were extracted from the cells and applied to two-dimensional gel electrophoresis (2DE). Those proteins with their expression levels altered at least 2-fold comparing to the control were picked up for protein identification via MALDI-TOF mass spectrometry and further confirmed by Western blot analysis. About 1000 spots were detected by the software in each 2DE gel, among which 13 differentially expressed proteins were identified by mass spectrometry and most of them are relevant to oxidative stress, such as peroxiredoxins, superoxide dismutase, quinolinate phosphoribosyl transferase, and D-dopachrome tautomerase. Meanwhile, reactive oxygen species (ROS) and mitochondrial membrane potential were also detected by flow cytometry and laser confocal scanning microscope. An increase in ROS generation and a decrease in mitochondrial membrane potential were detected in the selenite-treated cells compared with the control, which are consistent with the down-expression of antioxidative proteins in proteomics. Those results indicate that selenite induces the apoptosis of HeLa cells via ROS-mediated mitochondrial pathway. The present study also implies the potentiality of selenium in cervical cancer treatment.
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Effects of Chronic, Systemic Treatment with the Dopamine Receptor Agonist R-apomorphine in Partially Lesioned Rat Model of Parkinson's Disease: an Electrophysiological Study of Substantia Nigra Dopamine Neurons
The Chinese Journal of Physiology.
Apr, 2011 |
Pubmed ID: 21789890 Previous studies have suggested that R-apomorphine (R-APO), a non-selective dopamine (DA) receptor agonist, has neuroprotective effects in the experimental models of Parkinson's disease (PD). In this study, we investigated the effects of chronic, systemic treatment with R-APO in the firing activity of substantia nigra pars compacta (SNc) DA neurons in 6-hydroxydopamine (6-OHDA) partially lesioned rats. In the 6-OHDA-lesioned rats treated with vehicle, injection of 6-OHDA (20.1 microg) into the striatum produced a partial lesion causing 41% loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the SNc. In the partially lesioned rats, chronic, systemic treatment of R-APO (10 mg/kg/day, s.c., 11 days) attenuated loss of TH-ir neurons in the SNc. The partial lesion of the nigrostriatal pathway and R-APO treatment did not change the firing rate and firing pattern of DA neurons in the SNc of rats. In contrast, the R-APO treatment increased the number of spontaneously active DA neurons of the SNc in the partially lesioned rats, while the lesion decreased the number of spontaneously active DA neurons. In addition, the chronic R-APO treatment decreased the responsiveness of the DA neurons to intravenously administrated R-APO in the partially lesioned rats. These results indicate that chronic, systemic R-APO treatment has the neuroprotective effect, and reverses the decrease in the number of spontaneously active DA neurons in the SNc whereas the treatment induces a reduction in the sensitivity of DA receptors in the SNc to R-APO stimulation in this model.
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Mapping a Region of Hepatitis C Virus E2 That is Responsible for Escape from Neutralizing Antibodies and a Core CD81-binding Region That Does Not Tolerate Neutralization Escape Mutations
Journal of Virology.
Oct, 2011 |
Pubmed ID: 21813602 Understanding the interaction between broadly neutralizing antibodies and their epitopes provides a basis for the rational design of a preventive hepatitis C virus (HCV) vaccine. CBH-2, HC-11, and HC-1 are representatives of antibodies to overlapping epitopes on E2 that mediate neutralization by blocking virus binding to CD81. To obtain insights into escape mechanisms, infectious cell culture virus, 2a HCVcc, was propagated under increasing concentrations of a neutralizing antibody to isolate escape mutants. Three escape patterns were observed with these antibodies. First, CBH-2 escape mutants that contained mutations at D431G or A439E, which did not compromise viral fitness, were isolated. Second, under the selective pressure of HC-11, escape mutations progressed from a single L438F substitution at a low antibody concentration to double substitutions, L438F and N434D or L438F and T435A, at higher antibody concentrations. Escape from HC-11 was associated with a loss of viral fitness. An HCV pseudoparticle (HCVpp) containing the L438F mutation bound to CD81 half as efficiently as did wild-type (wt) HCVpp. Third, for HC-1, the antibody at a critical concentration completely suppressed viral replication and generated no escape mutants. Epitope mapping revealed contact residues for CBH-2 and HC-11 in two regions of the E2 glycoprotein, amino acids (aa) 425 to 443 and aa 529 to 535. Interestingly, contact residues for HC-1 were identified only in the region encompassing aa 529 to 535 and not in aa 425 to 443. Taken together, these findings point to a region of variability, aa 425 to 443, that is responsible primarily for viral escape from neutralization, with or without compromising viral fitness. Moreover, the region aa 529 to 535 is a core CD81 binding region that does not tolerate neutralization escape mutations.
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Diaqua-bis-(4-carb-oxy-2-ethyl-1H-imidazole-5-carboxyl-ato-κN,O)cadmium Dihydrate
Acta Crystallographica. Section E, Structure Reports Online.
Jul, 2011 |
Pubmed ID: 21836881 The asymmetric unit of the title compound, [Cd(C(7)H(7)N(2)O(4))(2)(H(2)O)(2)]·2H(2)O, consists of one Cd(II) ion, one 4-carb-oxy-2-ethyl-1H-imidazole-5-carboxyl-ate anion, one coordinated water mol-ecule and one lattice water mol-ecule. The Cd(II) ion lies on a twofold axis, and is hexa-coordinated by four O atoms from water mol-ecules and carboxyl-ate groups and two N atoms from two imidazole rings, in a distorted octa-hedral arrangement. An extensive framework of N-H⋯O and O-H⋯O hydrogen bonds with the participation of coordinated and free water mol-ecules is found in the crystal structure, which contributes to the formation of a three-dimensional structure.
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Predictive Value of D-dimer Test for Recurrent Venous Thromboembolism at Hospital Discharge in Patients with Acute Pulmonary Embolism
Journal of Thrombosis and Thrombolysis.
Nov, 2011 |
Pubmed ID: 21847593 D-dimer can be used to exclude acute pulmonary embolism (PE) for its high negative predictive value (NPV). Also, it is a predictor of recurrent venous thromboembolism (VTE) after anticoagulation withdrawal. The aim of the present study was to assess the predictive value of D-dimer for recurrent VTE when tested at hospital discharge. Plasma D-dimer levels were repeatedly measured at hospital discharge in 204 consecutive patients with the first episode of acute pulmonary embolism. Patients were categorized to two groups by D-dimer levels at hospital discharge and followed up at 3, 6, and 12 months and yearly thereafter. The primary end point was symptomatic, recurrent fatal or nonfatal VTE. D-dimer levels were persistently abnormal in 66 patients (32%). After 31±19 months follow-up, patients with persistently abnormal D-dimer level levels showed a higher rate of of recurrent VTE (14 patients, 21%) compared to those with D-dimer regression (8 patients, 6%) (P = 0.001). At the multivariate analysis, after adjustment for other relevant factors, persistently abnormal D-dimer level levels were an independent predictor of recurrent VTE in all subjects investigated, (hazard ratio, 4.10; 95% CI, 1.61-10.39; P = 0.003), especially in those with unprovoked PE (hazard ratio, 4.61; 95% CI, 1.85-11.49; P = 0.001). The negative predictive value of D-dimer was 94.2 and 92.9% in all subjects or those with unprovoked PE, respectively. Persistently abnormal D-dimer level levels at hospital discharge have a high negative predictive value for recurrence in patients with acute pulmonary embolism, especially in subjects with an unprovoked previous event.
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A Pilot Study of the Efficacy and Safety of Paroxetine Augmented with Risperidone, Valproate, Buspirone, Trazodone, or Thyroid Hormone in Adult Chinese Patients with Treatment-resistant Major Depression
Journal of Clinical Psychopharmacology.
Oct, 2011 |
Pubmed ID: 21869688 To compare the efficacy and safety of augmenting paroxetine with risperidone, buspirone, valproate, trazodone, or thyroid hormone in patients with treatment-resistant depression (TRD), 225 patients with retrospectively and/or prospectively identified stage II TRD were randomly assigned to receive an 8-week treatment of paroxetine 20 mg/d augmented with risperidone 2 mg/d (n = 45), sodium valproate 600 mg/d (n = 39), buspirone 30 mg/d (n = 46), trazodone 100 mg/d (n = 47), or thyroid hormone 80 mg/d (n = 48). The primary outcome was the remission rate defined as the 17-item Hamilton Rating Scale for Depression score of 7 or less at the end of study. Secondary outcomes included remission rate based on the Self-rating Depression Scale score of 50 or less at the end of study, response rate based on 17-item Hamilton Rating Scale for Depression total score of 50% improvement or greater from baseline, and the change in scores of Clinical Global Impression-Improvement scale, the Short Form 36 Health Survey, and the Life Satisfaction Rating Scale. The remission rates were 26.7% for risperidone, 48.7% for valproate, 32.6% for buspirone, 42.6% for trazodone, and 37.5% for thyroid hormone. There was no statistical significance among treatment arms in remission rates, secondary outcome measures, and adverse events. Risperidone, valproate, buspirone, trazodone, or thyroid hormone augmentation to paroxetine 20 mg/d was effective and well tolerated in Chinese patients with TRD. Large-sample studies are warranted to support or refute these findings.
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The Basic Helix-loop-helix Transcription Factor Family in the Pea Aphid, Acyrthosiphon Pisum
Journal of Insect Science (Online).
2011 |
Pubmed ID: 21870970 The basic helix-loop-helix (bHLH) proteins play essential roles in a wide range of developmental processes in higher organisms. bHLH family members have been identified in over 20 organisms, including fruit fly, zebrafish, and human. This study identified 54 bHLH family members in the pea aphid, Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae), genome. Phylogenetic analyses revealed that they belong to 37 bHLH families with 21, 13, 9, 1, 9, and 1 members in group A, B, C, D, E, and F, respectively. Through in-group phylogenetic analyses, all of the identified A. pisum bHLH members were assigned into their correspondent bHLH families with confidence, among which 51 were defined according to phylogenetic analyses with orthologs from Drosophila melanogaster Meigen (Diptera: Drosophilidae), and 3 of them were defined according to phylogenetic analyses with orthologs from Bombyx mori L. (Lepidoptera: Bombycidae) and Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). Analyses on genomic coding regions revealed that the number and average length of introns in A. pisum bHLH motifs are higher than those in other insects. The present study provides useful background information for future studies on structure and function of bHLH proteins in the regulation of A. pisum development.
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Noninvasive Electroanatomic Mapping of Human Ventricular Arrhythmias with Electrocardiographic Imaging
Science Translational Medicine.
Aug, 2011 |
Pubmed ID: 21885406 The rapid heartbeat of ventricular tachycardia (VT) can lead to sudden cardiac death and is a major health issue worldwide. Efforts to identify patients at risk, determine mechanisms of VT, and effectively prevent and treat VT through a mechanism-based approach would all be facilitated by continuous, noninvasive imaging of the arrhythmia over the entire heart. Here, we present noninvasive real-time images of human ventricular arrhythmias using electrocardiographic imaging (ECGI). Our results reveal diverse activation patterns, mechanisms, and sites of initiation of human VT. The spatial resolution of ECGI is superior to that of the routinely used 12-lead electrocardiogram, which provides only global information, and ECGI has distinct advantages over the currently used method of mapping with invasive catheter-applied electrodes. The spatial resolution of this method and its ability to image electrical activation sequences over the entire ventricular surfaces in a single heartbeat allowed us to determine VT initiation sites and continuation pathways, as well as VT relationships to ventricular substrates, including anatomical scars and abnormal electrophysiological substrate. Thus, ECGI can map the VT activation sequence and identify the location and depth of VT origin in individual patients, allowing personalized treatment of patients with ventricular arrhythmias.
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Tbx20 Transcription Factor is a Downstream Mediator for Bone Morphogenetic Protein-10 in Regulating Cardiac Ventricular Wall Development and Function
The Journal of Biological Chemistry.
Oct, 2011 |
Pubmed ID: 21890625 Bone morphogenetic protein 10 (BMP10) belongs to the TGFβ-superfamily. Previously, we had demonstrated that BMP10 is a key regulator for ventricular chamber formation, growth, and maturation. Ablation of BMP10 leads to hypoplastic ventricular wall formation, and elevated levels of BMP10 are associated with abnormal ventricular trabeculation/compaction and wall maturation. However, the molecular mechanism(s) by which BMP10 regulates ventricle wall growth and maturation is still largely unknown. In this study, we sought to identify the specific transcriptional network that is potentially mediated by BMP10. We analyzed and compared the gene expression profiles between α-myosin heavy chain (αMHC)-BMP10 transgenic hearts and nontransgenic littermate controls using Affymetrix mouse exon arrays. T-box 20 (Tbx20), a cardiac transcription factor, was significantly up-regulated in αMHC-BMP10 transgenic hearts, which was validated by quantitative RT-PCR and in situ hybridization. Ablation of BMP10 reduced Tbx20 expression specifically in the BMP10-expressing region of the developing ventricle. In vitro promoter analysis demonstrated that BMP10 was able to induce Tbx20 promoter activity through a conserved Smad binding site in the Tbx20 promoter proximal region. Furthermore, overexpression of Tbx20 in myocardium led to dilated cardiomyopathy that exhibited ventricular hypertrabeculation and an abnormal muscular septum, which phenocopied genetically modified mice with elevated BMP10 levels. Taken together, our findings demonstrate that the BMP10-Tbx20 signaling cascade is important for ventricular wall development and maturation.
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Do All the Protic Ionic Liquids Exist As Molecular Aggregates in the Gas Phase?
Physical Chemistry Chemical Physics : PCCP.
Oct, 2011 |
Pubmed ID: 21897972 According to an EI-MS study of 1,1,3,3-tetramethylguanidium-based protic ionic liquids (PILs), it has been concluded that not all PILs exist as molecular aggregates in the gas phase. The detection of both ions of m/z 115.0 and m/z 116.0 for the 1,1,3,3-tetramethylguanidinium trifluoromethylsulfonate (TMGS) protic ionic liquid indicates that both the molecular and ionic aggregates co-exist in the gas phase, which is to say that the TMGS may also evaporate via the ionic aggregates just like aprotic ionic liquids. Furthermore, investigation on triethylamine-based and 1-methylimidazole-based PILs confirmed that the gas phase structure of PILs depends on both the acidity and basicity of the corresponding acid and base.
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A B3LYP and MP2(full) Theoretical Investigation into Explosive Sensitivity Upon the Formation of the Molecule-cation Interaction Between the Nitro Group of 3,4-dinitropyrazole and H(+), Li (+), Na (+), Be (2+) or Mg (2+)
Journal of Molecular Modeling.
Sep, 2011 |
Pubmed ID: 21904813 The explosive sensitivity upon the formation of molecule-cation interaction between the nitro group of 3,4-dinitropyrazole (DNP) and H(+), Li(+), Na(+), Be(2+) or Mg(2+) has been investigated using the B3LYP and MP2(full) methods with the 6-311++G** and 6-311++G(2df,2p) basis sets. The bond dissociation energy (BDE) of the C3-N7 trigger bond has also been discussed for the DNP monomer and the corresponding complex. The interaction between the oxygen atom of nitro group and H(+) in DNP…H(+) is partly covalent in nature. The molecule-cation interaction and bond dissociation energy of the C3-N7 trigger bond follow the order of DNP…Be(2+) > DNP…Mg(2+) > DNP…Li(+) > DNP…Na(+). Except for DNP…H(+), the increment of the trigger bond dissociation energy in comparison with the DNP monomer correlates well with the molecule-cation interaction energy, natural charge of the nitro group, electron density Ï (BCP(C3-N7)), delocalization energy E ((2)) and NBO charge transfer. The analyses of atoms in molecules (AIM), natural bond orbital (NBO) and electron density shifts have shown that the electron density of the nitro group shifts toward the C3-N7 trigger bond upon the formation of the molecule-cation interaction. Thus, the trigger bond is strengthened and the sensitivity of DNP is reduced.
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The Effect of Zinc Addition on the Oxidation State of Cobalt in Co/ZrO2 Catalysts
ChemSusChem.
Nov, 2011 |
Pubmed ID: 21919212 The effect of zinc promotion on the oxidation state of cobalt in Co/ZrO(2) catalysts was investigated and correlated with the activity and selectivity for ethanol steam reforming (ESR). Catalysts were synthesized by applying incipient wetness impregnation and characterized by using Brunauer-Emmett-Teller (BET), temperature-programmed reduction (TPR) measurements, X-ray diffraction (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). Higher ethanol conversion and lower CH(4) selectivity are observed for the Co/ZrO(2) catalyst promoted with Zn as compared to the Co/ZrO(2) catalyst alone. Addition of Zn inhibits the oxidation of metallic cobalt (Co(0) ) particles and results in a higher ratio of Co(0) /Co(2+) in the Zn-promoted Co/ZrO(2) catalyst. These results suggest that metallic cobalt (Co(0) ) is more active than Co(2+) in the ethanol conversion through dehydrogenation and that Co(2+) may play a role in the CH(4) formation. TPR measurements, on the other hand, reveal that Zn addition inhibits the reduction of Co(2+) and Co(3+) , which would lead to the false conclusion that oxidized Co is required to reduce the CH(4) formation. Therefore, TPR measurements may not be appropriate to correlate the degree of metal reducibility (in this case Co(0)) with the catalyst activity for reactions, such as ESR, where oxidizing conditions exist.
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Association of Elevated NTproBNP with Recurrent Thromboembolic Events After Acute Pulmonary Embolism
Thrombosis Research.
Sep, 2011 |
Pubmed ID: 21955395 INTRODUCTION: N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP) is a predictor of adverse short-term clinical outcomes in patients with acute pulmonary embolism (APE), but its long-term prognostic value remains largely undefined. The aim of this study was to assess the value of plasma NTproBNP with regard to recurrent venous thromboembolism (VTE). MATERIALS AND METHODS: NTproBNP levels were measured in 224 consecutive patients with the first episode of acute pulmonary embolism occurring from January 2005 through October 2010. Patients were categorized into two groups by NTproBNP reference range. Follow-ups were performed at 3, 6, and 12months and yearly thereafter. The primary end point was symptomatic, recurrent fatal or nonfatal VTE. RESULTS: NTproBNP was elevated in 158 (70.5%) patients and not elevated in 66 (29.5%) patients. After a mean follow-up period of 31.0±19.4months, patients with elevated NTproBNP showed an increased risk of recurrent VTE (20 patients, 12.7%) compared to those without elevated NTproBNP (only 1 patient, 1.5%) (P=0.009). Of the 7 deaths related to pulmonary embolism, 6 occurred in patients with elevated NTproBNP compared to patients with normal NTproBNP (1 of 7 deaths). In a multivariate analysis stratified by oral anticoagulant treatment duration, elevated NTproBNP was an independent predictor of recurrent VTE (hazard ratio, 9.32; P=0.02). CONCLUSIONS: Elevated NTproBNP is associated with recurrent VTE in acute pulmonary embolism patients.
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Fast Synthesis of 1,3-DAG by Lecitase® Ultra-catalyzed Esterification in Solvent-free System
European Journal of Lipid Science and Technology : EJLST.
Aug, 2011 |
Pubmed ID: 21966255 Lecitase® Ultra, a phospholipase, was explored as an effective biocatalyst for direct esterification of glycerol with oleic acid to produce 1,3-DAG. Experiments were carried out in batch mode, and optimal reaction conditions were evaluated. In comparison with several organic solvent mediums, the solvent-free system was found to be more beneficial for this esterification reaction, which was further studied to investigate the reaction conditions including oleic acid/glycerol mole ratio, temperature, initial water content, enzyme load, and operating time. The results showed that Lecitase® Ultra catalyzed a fast synthesis of 1,3-DAG by direct esterification in a solvent-free medium. Under the optimal reaction conditions, a short reaction time 1.5 h was found to achieve the fatty acid esterification efficiency of 80.3 ± 1.2% and 1,3-DAG content of 54.8 ± 1.6 wt% (lipid layer of reaction mixture mass). The reusability of Lecitase® Ultra was evaluated via recycling the excess glycerol layer in the reaction system. DAG in the upper lipid layer of reaction mixture was purified by molecular distillation and the 1,3-DAG-enriched oil with a purity of about 75 wt% was obtained.Practical applications: The new Lecitase® Ultra catalyzed process for production of 1,3-DAG from glycerol and oleic acid described in this study provides several advantages over conventional methods including short reaction time, the absence of a solvents and a high product yield.
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A Novel Vaccine Delivery System: Biodegradable Nanoparticles in Thermosensitive Hydrogel
Growth Factors (Chur, Switzerland).
Dec, 2011 |
Pubmed ID: 21981422 In this work, a novel vaccine delivery system, biodegradable nanoparticles (NPs) in thermosensitive hydrogel, was investigated. Human basic fibroblast growth factor (bFGF)-loaded NPs (bFGF-NPs) were prepared, and then bFGF-NPs were incorporated into thermosensitive hydrogel to form bFGF-NPs in a hydrogel composite (bFGF-NPs/hydrogel). bFGF-NPs/hydrogel was an injectable sol at ambient temperature, but was converted into a non-flowing gel at body temperature. The in vitro release profile showed that bFGF could be released from bFGF-NPs or bFGF-NPs/hydrogel at an extended period, but the release rate of bFGF-NPs/hydrogel was much lower. In vivo experiments suggested that immunogenicity of bFGF improved significantly after being incorporated into the NPs/hydrogel composite, and strong humoral immunity was maintained for longer than 12 weeks. Furthermore, an in vivo protective anti-tumor immunity assay indicated that immunization with bFGF-NPs/hydrogel could induce significant suppression of the growth and metastases of tumors. Thus, the NPs/hydrogel composite may have great potential application as a novel vaccine delivery system.
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Skin-specifically Transgenic Expression of Biologically Active Human Cytoxic T-lymphocyte Associated Antigen4-Immunoglobulin (hCTLA4Ig) in Mice Using Lentiviral Vector
Transgenic Research.
Oct, 2011 |
Pubmed ID: 21983813 Xenogeneic skin, especially porcine skin, has already been used to cover large wounds in clinic practice of wound care. Our previous data showed that transgenic expression of human cytoxic T-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) in murine skin graft remarkably prolonged its survival in xenogeneic burn wounds without extensive immunosuppression in recipients, suggesting that transgenic hCTLA4Ig expression in skin graft may be an effective and safe method to prolong its survival in xenogeneic wounds for coverage. Lentiviral transgenesis provides an extremely efficient and cost-effective method to produce transgenic animals. However, tissue-targeted transgenic expression of biologically functional protein by lentiviral transgenesis is rarely reported. In this work, a recombinant lentiviral vector (LV), named FKCW in this article, was constructed by inserting a skin-specific hCTLA4Ig expression cassette consisting of keratin 14 (K14) promoter, hCTLA4Ig coding sequence and an intronic fragment. Its efficacy for transgenesis and skin-specific expression of bio-active hCTLA4Ig protein was tested using mice as models. The LV FKCW was readily to be packaged and concentrated to high titres (1.287-6.254 × 10(9) TU/ml) by conventional lentivirus package system. Using eggs collected from only five mated females having been subjected to conventional super-ovulation treatment, 8 hCTLA4Ig transgenic founder mice were generated with the concentrated FKCW vector, and transgenic founder per injected and transferred egg was 6.3%, which was nearly 9-fold higher than that for DNA micro-injection with a similar transgene construct in our previous work. The lentiviral transgenic hCTLA4Ig exhibited strictly skin-specific expression at a level comparable to or even slightly higher than that of transgenic hCTLA4Ig delivered by micro-injection in a similar cassette. Lentiviral transgenic hCTLA4Ig protein remarkably suppressed human lymphocyte proliferation in vitro to a degree comparable to that of commercially purchased purified hCTLA4Ig protein with defined activity at similar concentrations. Besides, lentiviral hCTLA4Ig transgenic mouse skin grafted into rat burn wounds exhibited remarkably extended survival compared to wild-type skin of the same strain (13.8 ± 3.8 vs. 6.8 ± 3.0 days), indicating that lentiviral transgenic hCTLA4Ig did inhibit immune rejection against xenogeneic skin graft in vivo. These results laid down the foundation to further efficiently generate transgenic pigs skin-specifically expressing bio-active hCTLA4Ig by lentiviral transgenesis, and provided a demonstration that transgenic animals with tissue-targeted expression of biologically functional protein can be efficiently produced using LV.
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Involvement of a Helix-loop-helix Transcription Factor CHC-1 in CO(2)-mediated Conidiation Suppression in Neurospora Crassa
Fungal Genetics and Biology : FG & B.
Dec, 2011 |
Pubmed ID: 22001287 The morphological switch from vegetative growth to conidiation in filamentous fungi is highly regulated, but the understanding of the regulatory mechanisms is limited. In this study, by screening a set of knock-out mutants corresponding to 103 transcription factor encoding genes in Neurospora crassa, a mutant was found to produce abundant conidia in race tubes in which conidiation in the wild-type strain was suppressed. The corresponding gene NCU00749 encodes a protein containing a helix-loop-helix DNA binding region. Unlike enhanced conidiation in ras-1 and sod-1 mutants, which was completely suppressed by antioxidant N-acetyl cysteine, enhanced conidiation in the NCU00749 mutant was only slightly affected by N-acetyl cysteine. When grown on slants, the NCU00749 deletion mutant exhibited earlier conidial formation than the wild-type strain, and this was more evident at a higher (5%) CO(2) concentration. Therefore, we named NCU00749 as conidiation at high carbon dioxide-1 (chc-1). Genes that are highly expressed during conidial development, eas, con-6, con-8 and con-10, were transcribed at a higher rate in the chc-1 deletion mutant than the wild-type strain in response to conidiation induction. To determine the mechanisms by which CHC-1 regulates conidiation, we conducted a RNA sequencing analysis and found that 404 genes exhibited ≥ 2 fold changes in transcription in response to chc-1 deletion. Among them, fluffy and ada-6, two transcription factor genes that positively regulate conidiation in N. crassa, and rca-1, whose homolog flbD in Aspergillus nidulans is essential for conidiation, were upregulated in the chc-1 deletion mutant. Results of RNA sequencing also suggest that signal transduction via the cAMP and the MAK-2 mediated signal pathways, and ROS generation and removal, mechanisms known to regulate conidiation, are not involved in chc-1 mediated control of conidiation. In addition, chc-1 also influences expression of genes involved in other important biological processes besides conidiation such as carbon metabolism, sphingolipid synthesis, cell wall synthesis, and calcium signaling.
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Upregulation of IRS-1 Expression in Goto-Kakizaki Rats Following Roux-en-Y Gastric Bypass Surgery: Resolution of Type 2 Diabetes?
The Tohoku Journal of Experimental Medicine.
2011 |
Pubmed ID: 22001674 Type 2 diabetes mellitus (T2DM) is an endocrine disorder that is rapidly growing in prevalence within China and throughout the world. Roux-en-Y gastric bypass (RYGB) surgery, widely used in the treatment of obesity, has been recognized as an effective and long-term treatment for T2DM in recent years. However, the underlying mechanisms responsible for glycemic control remain unclear. This study was designed to investigate the roles of insulin receptor substrates (IRSs) in glucose tolerance and insulin resistance following RYGB surgery. Goto-Kakizaki (GK) rats, a model of T2DM, were randomly allocated into three groups: RYGB surgery, sham surgery, and control (10 animals/group). Wistar rats were also used as non-diabetic control. Daily food intake, body weight, glucose and insulin were measured pre- and post-operatively. Insulin receptor substrate 1 (IRS-1) and insulin receptor substrate 2 (IRS-2) content, the main subtypes of IRSs, were measured in skeletal muscle, adipose tissue and liver using western immunoblot analyses on postoperative day 28. Following surgery, RYGB-treated rats showed markedly improved oral glucose tolerance, as judged by lower peak and area-under-the-curve glucose values (p < 0.01 vs. GK or GK sham). Improved insulin resistance was also observed in RYGB-treated rats. Western immunoblot analyses showed that IRS-1 and its phosphorylation levels were significantly increased in skeletal muscle and adipose tissues in RYGB group (p < 0.01 vs. GK or GK sham), whereas IRS-2 levels were downregulated in liver. These findings suggest that improvements in glucose tolerance and insulin resistance following RYGB surgery are associated with upregulation of IRS-1.
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Affinity Maturation to Improve Human Monoclonal Antibody Neutralization Potency and Breadth Against Hepatitis C Virus
The Journal of Biological Chemistry.
Dec, 2011 |
Pubmed ID: 22002064 A potent neutralizing antibody to a conserved hepatitis C virus (HCV) epitope might overcome its extreme variability, allowing immunotherapy. The human monoclonal antibody HC-1 recognizes a conformational epitope on the HCV E2 glycoprotein. Previous studies showed that HC-1 neutralizes most HCV genotypes but has modest potency. To improve neutralization, we affinity-matured HC-1 by constructing a library of yeast-displayed HC-1 single chain Fv (scFv) mutants, using for selection an E2 antigen from one of the poorly neutralized HCVpp. We developed an approach by parallel mutagenesis of the heavy chain variable (VH) and κ-chain variable (Vk) genes separately, then combining the optimized VH and Vk mutants. This resulted in the generation of HC-1-related scFv variants exhibiting improved affinities. The best scFv variant had a 92-fold improved affinity. After conversion to IgG1, some of the antibodies exhibited a 30-fold improvement in neutralization activity. Both surface plasmon resonance and solution kinetic exclusion analysis showed that the increase in affinity was largely due to a lowering of the dissociation rate constant, Koff. Neutralization against a panel of HCV pseudoparticles and infectious 2a HCV virus improved with the affinity-matured IgG1 antibodies. Interestingly, some of these antibodies neutralized a viral isolate that was not neutralized by wild-type HC-1. Moreover, propagating 2a HCVcc under the selective pressure of WT HC-1 or affinity-matured HC-1 antibodies yielded no viral escape mutants and, with the affinity-matured IgG1, needed 100-fold less antibody to achieve complete virus elimination. Taken together, these findings suggest that affinity-matured HC-1 antibodies are excellent candidates for therapeutic development.
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Construction and Evaluation of a Multistage Mycobacterium Tuberculosis Subunit Vaccine Candidate Mtb10.4-HspX
Vaccine.
Nov, 2011 |
Pubmed ID: 22024175 To search for more effective vaccines to enhance the immunogenicity and protective efficacy of Mycobacterium bovis Bacille Calmette-Guerin (BCG) and to control or even eradicate Mycobacterium tuberculosis (M. tuberculosis) in all stages of infection including the persister bacteria, antigens of Mtb10.4 (Rv0288) expressed in replicating bacilli and HspX (also called Acr, Hsp16.3, Rv2031c) highly expressed in dormant bacilli were fused together to construct a multistage fusion protein Mtb10.4-HspX (MH for short) without affinity tag with potential advantage for clinical use. The human T-cell responses to MH were evaluated for its immunogenicity. Furthermore, MH was emulsified in an adjuvant composed of N,N'-dimethyl-N,N'-dioctadecylammonium bromide (DDA) and mycobacterial cord factor trehalose-6,6-dimycolate (TDM) to construct subunit vaccine, whose immunogenicity and potency to boost BCG primed immunity against M. tuberculosis infection were evaluated in mice. The results showed that the fusion protein MH without affinity tag was stably produced in Escherichia coli and was successfully purified by chromatography. MH was strongly recognized by human T cells from TB patients and persons latently infected with M. tuberculosis. In conclusion, MH in adjuvant DDA-TDM generated strong antigen-specific humoral and cell-mediated immunity, and had the capability to enhance BCG-primed immunity and the protective efficacy against M. tuberculosis in mice. These findings suggest that MH in DDA-TDM have the potential to be a good multistage tuberculosis vaccine candidate.
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A New Eudesmane Sesquiterpene Glucoside from Liriope Muscari Fibrous Roots
Molecules (Basel, Switzerland).
2011 |
Pubmed ID: 22031065 The screening of several Chinese medicinal herbs for nematocidal properties showed that the ethanol extract of Liriope muscari fibrous roots possessed significant nematocidal activity against the pine wood nematode (Bursaphelenchus xylophilus). From the ethanol extract, a new constituent (1,4-epoxy-cis-eudesm-6-O-β-D-glucopyranoside) and three known glycosides [1β,6α-dihydroxy-cis-eudesm-3-ene-6-O-β-D-glucopyranoside (liriopeoside A), 1β,6β-dihydroxy-cis-eudesm-3-ene-6-O-β-D-glucopyranoside, and 1α,6β-dihydroxy-5,10-bis-epi-eudesm-4(15)-ene-6-O-β D-glucopyranoside] were isolated by bioassay-guided fractionation. The structures were elucidated by 1D and 2D NMR and MS techniques. 1,4-Epoxy-cis-eudesm-6-O-β-D-glucopyranoside possessed moderate nemato-cidal activity against B. xylophilus with a LC(50 )value of 339.76 μg/mL, while liriopeoside A (LC(50) = 82.84 μg/mL) and 1β,6β-dihydroxy-cis-eudesm-3-ene-6-O-β-D-glucopyranoside (LC(50) = 153.39 μg/mL) also exhibited nematocidal activity against B. xylophilus. The crude extract of L. muscari fibrous roots exhibited nematocidal activity against the pine wood nematode with a LC(50) value of 182.56 μg/mL.
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A Genome-wide Survey on Basic Helix-loop-helix Transcription Factors in Giant Panda
PloS One.
2011 |
Pubmed ID: 22096504 The giant panda (Ailuropoda melanoleuca) is a critically endangered mammalian species. Studies on functions of regulatory proteins involved in developmental processes would facilitate understanding of specific behavior in giant panda. The basic helix-loop-helix (bHLH) proteins play essential roles in a wide range of developmental processes in higher organisms. bHLH family members have been identified in over 20 organisms, including fruit fly, zebrafish, mouse and human. Our present study identified 107 bHLH family members being encoded in giant panda genome. Phylogenetic analyses revealed that they belong to 44 bHLH families with 46, 25, 15, 4, 11 and 3 members in group A, B, C, D, E and F, respectively, while the remaining 3 members were assigned into "orphan". Compared to mouse, the giant panda does not encode seven bHLH proteins namely Beta3a, Mesp2, Sclerax, S-Myc, Hes5 (or Hes6), EBF4 and Orphan 1. These results provide useful background information for future studies on structure and function of bHLH proteins in the regulation of giant panda development.
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Kernel-based Data Fusion Improves the Drug-protein Interaction Prediction
Computational Biology and Chemistry.
Dec, 2011 |
Pubmed ID: 22099632 Proteins are involved in almost every action of every organism by interacting with other small molecules including drugs. Computationally predicting the drug-protein interactions is particularly important in speeding up the process of developing novel drugs. To borrow the information from existing drug-protein interactions, we need to define the similarity among proteins and the similarity among drugs. Usually these similarities are defined based on one single data source and many methods have been proposed. However, the availability of many genomic and chemogenomic data sources allows us to integrate these useful data sources to improve the predictions. Thus a great challenge is how to integrate these heterogeneous data sources. Here, we propose a kernel-based method to predict drug-protein interactions by integrating multiple types of data. Specially, we collect drug pharmacological and therapeutic effects, drug chemical structures, and protein genomic information to characterize the drug-target interactions, then integrate them by a kernel function within a support vector machine (SVM)-based predictor. With this data fusion technology, we establish the drug-protein interactions from a collections of data sources. Our new method is validated on four classes of drug target proteins, including enzymes, ion channels (ICs), G-protein couple receptors (GPCRs), and nuclear receptors (NRs). We find that every single data source is predictive and integration of different data sources allows the improvement of accuracy, i.e., data integration can uncover more experimentally observed drug-target interactions upon the same levels of false positive rate than single data source based methods. The functional annotation analysis indicates that our new predictions are worthy of future experimental validation. In conclusion, our new method can efficiently integrate diverse data sources, and will promote the further research in drug discovery.
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Design and Synthesis of Dual-ligand Modified Chitosan As a Liver Targeting Vector
Journal of Materials Science. Materials in Medicine.
Nov, 2011 |
Pubmed ID: 22105225 Vector plays an important role in hepatic targeted drug delivery system. In this study, a novel material as a liver targeting vector, dual-ligand modified chitosan (GCGA) composed of chitosan (CTS), glycyrrhetinic acid (GA) and lactobionic acid (LA), was designed and synthesized by an orthogonal experiment with two-step synthesis under mild conditions. The synthesized final product was characterized and confirmed by FTIR and (1)H-NMR spectroscopy, and DS of GA and LA in CTS were measured to be 13.77 and 16.74Â mol% using (1)H-NMR, respectively. The cytotoxicity of CTS and GCGA was concentration dependent which was inverse proportion to the cell viability by MTT assay using L929 cell line, and inhibitory concentration 50% (IC50) was 0.2Â mg/ml for GCGA. The in vitro targeting efficiency and the in vitro cellular uptake were investigated. Compared with CTS NPs and GA-CTS NPs, GCGA NPs showed good cell specificity to BEL-7402 cells via the dual-ligand-receptor-mediated recognition, leading to a higher affinity to BEL-7402 cells. The results suggested that GCGA described here has the potential to be used as an effective vector for hepatic targeted drug therapy.
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Blockade of MGluR5 Reverses Abnormal Firing of Subthalamic Nucleus Neurons in 6-hydroxydopamine Partially Lesioned Rats
The Chinese Journal of Physiology.
Oct, 2011 |
Pubmed ID: 22135908 Activation of metabotropic glutamate receptor 5 (mGluRs) in the subthalamic nucleus (STN) results in burst-firing activity of STN neurons, which is similar to that observed in Parkinson's disease (PD). We examined the effects of chronic and systemic treatment with 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective mGluR5 antagonist, in firing activity of STN neurons in partially lesioned rats by 6-hydroxydopamine (6-OHDA). In 6-OHDA-lesioned rats treated with vehicle, injection of 6-OHDA (4 microg) into the medial forebrain bundle produced a partial lesion causing 36% loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc). The 6-OHDA lesion in vehicle-treated rats showed an increasing firing rate and a more irregular firing pattern of STN neurons. Whereas chronic, systemic treatment of MPEP (3 mg/kg/day, 14 days) produced neuroprotecive effects on the TH-ir neurons and normalized the hyperactive firing activity of STN neurons in 6-OHDA partially lesioned rats. These data demonstrate that partial lesion of the nigrostriatal pathway increases firing activity of STN neurons in the rat, and chronic, systemic MPEP treatment has the neuroprotective effect and reverses the abnormal firing activity of STN neurons, suggesting that MPEP has an important implication for the treatment of PD.
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In Vitro Effects of Aqueous Extracts of Astragalus Membranaceus and Scutellaria Baicalensis GEORGI on Toxoplasma Gondii
Parasitology Research.
Dec, 2011 |
Pubmed ID: 22179265 Toxoplasma gondii is a parasite that infects animals and humans worldwide. The standard treatment for toxoplasmosis is limiting due to toxic adverse effects, thus there is a need to identify new drugs that are less toxic. Both Astragalus membranaceus and Scutellaria baicalensis GEORGI are popular traditional Chinese herbs widely used for the treatment of various inflammatory diseases in Asia, and we have previously demonstrated that water extracts of A. membranaceus (AmE) and S. baicalensis GEORGI (SbE) have good efficacy in controlling T. gondii replication in mouse models. This study was designed to further evaluate their effects against developing tachyzoites of the RH strain of T. gondii in HeLa cell cultures. AmE, SbE, and TMP-SMX (trimethoprim-sulfamethoxazole) were added into the wells containing both HeLa cells and replicating T. gondii of green fluorescent protein (GFP)-expressing RH tachyzoites. The proliferation and morphous of the tachyzoites were observed, the fluorescence intensity expressed as the fluorescence gray scale value was measured, and the living tachyzoites were counted at different culture times after treatment. The results showed that, compared to untreated controls, parasites treated with either AmE or SbE had significantly decreased intracellular replication at 72, 96, and 120 h after treatment (P 
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Supramolecular Micellar Nanoaggregates Based on a Novel Chitosan/vitamin E Succinate Copolymer for Paclitaxel Selective Delivery
International Journal of Nanomedicine.
2011 |
Pubmed ID: 22228999 Nowadays, many cytotoxic anticancer drugs exhibit low solubility and poor tumor selectivity, which means that the drug formulation is very important. For example, in the case of paclitaxel (PTX), Cremophor EL(®) (BASF, Ludwigshafen, Germany) needs to be used as a solubilizer in its clinical formulation (Taxol(®), Bristol-Myers Squibb, New York, NY), although it can cause serious side effects. Nanomicellar systems are promising carriers to resolve the above problems, and the polymer chosen is the key element.
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P38 MAPK Regulates Calcium Signal-mediated Lipid Accumulation Through Changing VDR Expression in Primary Preadipocytes of Mice
Molecular Biology Reports.
Mar, 2012 |
Pubmed ID: 21701827 In the present study we have examined whether p38 mitogen activated protein kinase (p38 MAPK) signal pathway interacts with calcium signal on lipid accumulation in primary preadipocytes of mice. The primary preadipocytes were treated with p38 MAPK inhibitor SB203580, blockers and excitomotors of calcium channel for 24 h, respectively. Intracellular triglyceride (TG) content was measured by triglyceride kit and lipid accumulation was determined by Oil Red O staining. Meanwhile, the mRNA expressions of peroxisome proliferators-activated receptor gamma (PPARγ) gene, fatty acid synthetase (FAS) gene, lipoprotein lipase (LPL) gene, vitamin D receptor (VDR) gene and extracellular Ca(2+)-sensing receptor (CaSR) gene were analyzed with real-time PCR. The protein content and phosphorylation of VDR and p38 were tested with Western Blotting. The data showed that intracellular TG content and the mRNA expression levels of PPARγ, FAS, LPL in N group and L group as well as FAS, LPL in C group were increased significantly (PÂ
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A Dynamic Hybrid Framework for Constrained Evolutionary Optimization
IEEE Transactions on Systems, Man, and Cybernetics. Part B, Cybernetics : a Publication of the IEEE Systems, Man, and Cybernetics Society.
Feb, 2012 |
Pubmed ID: 21824851 Based on our previous work, this paper presents a dynamic hybrid framework, called DyHF, for solving constrained optimization problems. This framework consists of two major steps: global search model and local search model. In the global and local search models, differential evolution serves as the search engine, and Pareto dominance used in multiobjective optimization is employed to compare the individuals in the population. Unlike other existing methods, the above two steps are executed dynamically according to the feasibility proportion of the current population in this paper, with the purpose of reasonably distributing the computational resource for the global and local search during the evolution. The performance of DyHF is tested on 22 benchmark test functions. The experimental results clearly show that the overall performance of DyHF is highly competitive with that of a number of state-of-the-art approaches from the literature.
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NFBD1/MDC1 is a Protein of Oncogenic Potential in Human Cervical Cancer
Molecular and Cellular Biochemistry.
Jan, 2012 |
Pubmed ID: 21853275 A large nuclear protein of 2089 amino acids, NFBD1/MDC1 has recently been implicated in tumorigenesis and tumor growth. In this study, we investigated its expression in cervical cancers and explored its function using gene knockdown approaches. We report here that NFBD1 expression is substantial increased in 24 of 39 cases (61.5%) of cervical cancer tissues at the mRNA level and in 35 of 60 cases (58.3%) at the protein level compared with the case matched normal tissues. Tumors with higher grade of malignancy tend to have higher levels of NFBD1 expression. By infecting cells with retroviruses expressing NFBD1 shRNA, we successfully knocked down NFBD1 expression in cervical cancer cell lines HeLa, SiHa, and CaSki. NFBD1 knockdown cells display significant growth inhibition, cell cycle arrest, higher apoptotic rate, and enhanced sensitivity to adriamycin. Furthermore, NFBD1 knockdown also inhibits the growth of HeLa cells in nude mice. Western blot analyses further revealed that NFBD1 knockdown induced Bax, Puma, and Noxa while down-regulating Bcl-2; it also up-regulated cytochrome C and activated caspases 3 and 9. Therefore, the function of NFBD1 may be involved in the CDC25C-CyclinB1/CDC2 pathway at the G2/M checkpoint, and the cytochrome C/caspase 3 apoptotic pathway. Since expression of NFBD1 seems to be related to the oncogenic potential of cervical cancer, and suppression of its expression can inhibit cancer cell growth both in vitro and in vivo, NFBD1 may be a potential therapeutic target in human cervical cancer.
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A Large Sample Volume Magic Angle Spinning Nuclear Magnetic Resonance Probe for in Situ Investigations with Constant Flow of Reactants
Physical Chemistry Chemical Physics : PCCP.
Feb, 2012 |
Pubmed ID: 22025270 A large-sample-volume constant-flow magic angle sample spinning (CF-MAS) NMR probe is reported for in situ studies of the reaction dynamics, stable intermediates/transition states, and mechanisms of catalytic reactions. In our approach, the reactants are introduced into the catalyst bed using a fixed tube at one end of the MAS rotor while a second fixed tube, linked to a vacuum pump, is attached at the other end of the rotor. The pressure difference between both ends of the catalyst bed inside the sample cell space forces the reactants flowing through the catalyst bed, which improves the diffusion of the reactants and products. This design allows the use of a large sample volume for enhanced sensitivity and thus permitting in situ(13)C CF-MAS studies at natural abundance. As an example of application, we show that reactants, products and reaction transition states associated with the 2-butanol dehydration reaction over a mesoporous silicalite supported heteropoly acid catalyst (HPA/meso-silicalite-1) can all be detected in a single (13)C CF-MAS NMR spectrum at natural abundance. Coke products can also be detected at natural (13)C abundance and under the stopped flow condition. Furthermore, (1)H CF-MAS NMR is used to identify the surface functional groups of HPA/meso-silicalite-1 under the condition of in situ drying. We also show that the reaction dynamics of 2-butanol dehydration using HPA/meso-silicalite-1 as a catalyst can be explored using (1)H CF-MAS NMR.
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RROP2(186-533): a Novel Peptide Antigen for Detection of IgM Antibodies Against Toxoplasma Gondii
Foodborne Pathogens and Disease.
Jan, 2012 |
Pubmed ID: 22085219 Toxoplasma gondii infections are prevalent in a wide range of mammalian hosts including humans. Infection in pregnant women may cause the transmission of parasite to the fetus that makes serious problems. IgM antibodies against Toxoplasma (Toxo-IgM) have been believed to be significant indicators for both recently acquired and congenital toxoplasmosis. So far, however, there has not been any recognized protein of T. gondii that specifically reacts to IgM antibodies. Here, an antigen exclusively for detection of IgM antibodies screened by two-dimensional electrophoresis and mass spectrometry has been reported. The study identified 13 Toxoplasma proteins probed by IgG antibodies and one (rhpotry protein 2 [ROP2]) by IgM antibodies with human sera of Toxo-IgM(-)-IgG(+) and -IgM(+)-IgG(-), respectively, which had been prescreened by Toxo-IgM and -IgG commercial kits from the suspected cases. Following cloning, expression, and purification of the fragment of ROP2(186-533), an enzyme-linked immunosorbent assay with rROP2(186-533) to measure IgM and IgG antibodies was developed. As a result, 100%(48/48) of sera with Toxo-IgM(+)-IgG(-)showed positive Toxo-IgM but none of them (0%) showed positive Toxo-IgG when rROP2(186-533) was used as antigen. Neither Toxo-IgG nor Toxo-IgM antibodies were found when tested with 59 sera of Toxo-IgM(-)-IgG(+). These results indicate that rROP2(186-533) could be used as an antigen that specifically capture Toxo-IgM antibodies and may have a high potential in the serological diagnosis of both acute acquired and congenital toxoplasmosis.
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Polymeric Graphitic Carbon Nitride As a Heterogeneous Organocatalyst: from Photochemistry to Multipurpose Catalysis to Sustainable Chemistry
Angewandte Chemie (International Ed. in English).
Jan, 2012 |
Pubmed ID: 22109976 Polymeric graphitic carbon nitride materials (for simplicity: g-C(3)N(4)) have attracted much attention in recent years because of their similarity to graphene. They are composed of C, N, and some minor H content only. In contrast to graphenes, g-C(3)N(4) is a medium-bandgap semiconductor and in that role an effective photocatalyst and chemical catalyst for a broad variety of reactions. In this Review, we describe the "polymer chemistry" of this structure, how band positions and bandgap can be varied by doping and copolymerization, and how the organic solid can be textured to make it an effective heterogenous catalyst. g-C(3)N(4) and its modifications have a high thermal and chemical stability and can catalyze a number of "dream reactions", such as photochemical splitting of water, mild and selective oxidation reactions, and--as a coactive catalytic support--superactive hydrogenation reactions. As carbon nitride is metal-free as such, it also tolerates functional groups and is therefore suited for multipurpose applications in biomass conversion and sustainable chemistry.
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Loperamide, an Antidiarrhea Drug, Has Antitumor Activity by Inducing Cell Apoptosis
Pharmacological Research : the Official Journal of the Italian Pharmacological Society.
Mar, 2012 |
Pubmed ID: 22119769 Loperamide, an antidiarrhea drug, is a peripheral opiate agonist. Some other opiate agonists have been shown to promote cell apoptosis. In this research, we studied the apoptosis-inducing and cytotoxic activities of loperamide. MTT assay was used to determine its cytotoxicity on nine established human tumor cell lines. Cell apoptosis was detected by flow cytometry. Hypodiploid cells and cell cycles were analyzed by propidium iodide (PI) staining, while early apoptotic cells were detected by annexin V-FITC/PI staining. It was found that loperamide could inhibit the proliferation of the tested tumor cell lines. The IC(50) values for SMMC7721, MCF7, SPC-A1, SKOV3-DDP, H460, HepG2, SGC7901, U2OS, and ACHN cells were 24.2±2.1μM, 23.6±2.5μM, 25.9±3.1μM, 27.1±2.5μM, 41.4±2.1μM, 23.7±1.3μM, 35.4±3.5μM, 11.8±2.8μM, and 28.5±3.4μM, respectively. Loperamide was more effective to the human osteosarcoma U2OS cells with an IC(50) value of 11.8±2.8μM. Meanwhile, it could induce cell apoptosis and cause G2/M-phase cell cycle arrest. The apoptotic cells could be found when treating with loperamide for 6h and most of them belonged to early apoptosis. In loperamide-treated cells, activation of caspase-3 was found, namely that caspase-3 was involved in the loperamide-induced apoptosis. The results of these studies indicate that loperamide is a potential antitumor agent. To our knowledge, this is the first report on antitumor activity of loperamide.
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Revelation of Topological Surface States in Bi(2)se(3) Thin Films by in Situ Al Passivation
ACS Nano.
Jan, 2012 |
Pubmed ID: 22147687 Topological insulators (TIs) are extraordinary materials that possess massless, Dirac-like topological surface states in which backscattering is prohibited due to the strong spin-orbit coupling. However, there have been reports on degradation of topological surface states in ambient conditions, which presents a great challenge for probing the original topological surface states after TI materials are prepared. Here, we show that in situ Al passivation inside a molecular beam epitaxy (MBE) chamber could inhibit the degradation process and reveal the pristine topological surface states. Dual evidence from Shubnikov-de Hass (SdH) oscillations and weak antilocalization (WAL) effect, originated from the π Berry phase, suggests that the helically spin-polarized surface states are well preserved by the proposed in situ Al passivation. In contrast, we show the degradation of surface states for the unpassivated control samples, in which the 2D carrier density is increased 39.2% due to ambient n-doping, the SdH oscillations are completely absent, and a large deviation from WAL is observed.
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Probing Biomolecular Interactions with Dual Polarization Interferometry: Real-time and Label-free Coralyne Detection by Use of Homoadenine DNA Oligonucleotide
Analytical Chemistry.
Jan, 2012 |
Pubmed ID: 22148232 We incorporated the specific recognition of adenine-rich singled-stranded DNA (ssDNA) into dual polarization interferometry (DPI) measurements for direct, selective, and sensitive detection of the small molecule coralyne, and we simultaneously employed the real-time and label-free technique for detailed investigation of the interaction between coralyne and adenine-rich ssDNA. Data from UV-visible spectroscopy, circular dichroism (CD) spectroscopy, and DNA melting firmly confirmed that 48-mer homoadenine ssDNA oligonucleotide (A(48)) had highly specific recognition for coralyne, whereas 48-mer homothymine ssDNA oligonucleotide (T(48)) as the control had no such recognition. The immobilization of ssDNA (A(48) or T(48)) on a silicon oxynitride chip could be achieved through a preadsorbed poly(ethylenimine) (PEI) layer. Mass, thickness, and refractive index (RI) changes resolved by DPI during the whole process of ssDNA immobilization suggested that most ssDNA molecules were likely to lie on the PEI surface mainly in the form of a flat monolayer and insert themselves partly into the PEI layer. Qualitative and quantitative analysis of mass, thickness, and RI changes in A(48)/PEI layer upon addition of different concentrations of coralyne revealed that A(48) most likely underwent a conformational change from single-stranded to double-stranded structure. By evaluation of the binding curves from changes in mass, the association rate constant (k(a)), dissociation rate constant (k(d)), and association constant (K(A)) between coralyne and A(48) were determined to be 4.95 × 10(3) M(-1) s(-1), 0.031 s(-1), and 1.6 × 10(5) M(-1), respectively. Good linear correlations between coralyne concentrations ranging from 0.5 to 12 μM and three parameters (mass, thickness, and RI) resolved by the response to coralyne binding were obtained. The detection limits were 0.22 μM for mass calibration, 0.14 μM for thickness calibration, and 0.32 μM for RI calibration. The high selectivity of the biosensor to coralyne at the A(48)/PEI interface was successfully confirmed by using the other two interfaces (T(48)/PEI and PEI) and three typical intercalators (ethidium bromide, daunomycin, and methylene blue). It is expected that the biosensing platform may be extended to simultaneously detect and characterize the interactions of a variety of target molecules with functional DNA molecules with high sensitivity.
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Estradiol Directly Attenuates Sodium Currents and Depolarizing Afterpotentials in Isolated Gonadotropin-releasing Hormone Neurons
Brain Research.
Feb, 2012 |
Pubmed ID: 22209345 The gonadotropin-releasing hormone (GnRH) neuron is the pivotal control center in a tightly regulated reproductive axis. The release of GnRH controls estradiol production by the ovary, and estradiol acts at the hypothalamus to regulate GnRH release. However, the mechanisms of estradiol feedback are just beginning to be understood. We have previously shown that estradiol administered to the female mouse modulates sodium currents in fluorescently-labeled GnRH neurons. In the current studies, estradiol (1nM) was applied directly, for 16-24h, to hypothalamic cultures from young or aged female ovariectomized mice. The direct application of estradiol modulated a tetrodotoxin-sensitive sodium current in isolated GnRH neurons from both young and aged animals. Estradiol, and the specific estrogen receptor-β agonist DPN, decreased current amplitude measured in the morning (AM), but had no effect on afternoon currents. These compounds also decreased the rise and decay slope of the current response, increased the width of the current, and increased action potential width in AM recordings. In addition, estradiol decreased the amplitude of the depolarizing afterpotential (DAP); this effect was not time-of-day dependent. The ER-β agonist DPN did not mimic the effect of estradiol on DAPs, and the modulation of DAPs by estradiol was no longer present in cells from postreproductive animals. These results indicate that estradiol can affect the physiology of GnRH neurons via multiple pathways that are differentially regulated during the transition to reproductive senescence, suggesting that estradiol regulation of GnRH neuronal output is modulated during the aging process.
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Water-dispersible, Uniform Nanospheres by Heating-enabled Micellization of Amphiphilic Block Copolymers in Polar Solvents
Langmuir : the ACS Journal of Surfaces and Colloids.
Feb, 2012 |
Pubmed ID: 22211314 Uniform nanospheres with tunable size down to 30 nm were prepared simply by heating amphiphilic block copolymers in polar solvents. Unlike reverse micelles prepared in nonpolar, oily solvents, these nanospheres have a hydrophilic surface, giving them good dispersibility in water. Furthermore, they are present as individual, separated, rigid particles upon casting from the solution other than continuous thin films of merged micelles cast from micellar solution in nonpolar solvents. These nanospheres were generated by a heating-enabled micellization process in which the affinity between the solvent and the polymer chains as well as the segmental mobility of both hydrophilic and hydrophobic blocks was enhanced, triggering the micellization of the glassy copolymers in polar solvents. This heating-enabled micellization produces purely well-defined nanospheres without interference of other morphologies. The micelle sizes and corona thickness are tunable mainly by changing the lengths of the hydrophobic and hydrophilic blocks, respectively. The heating-enabled micellization route for the preparation of polymeric nanospheres is extremely simple, and is particularly advantageous in producing rigid, micellar nanospheres from block copolymers with long glassy, hydrophobic blocks which are otherwise difficult to prepare with high efficiency and purity. Furthermore, encapsulation of hydrophobic molecules (e.g., dyes) into micelle cores could be integrated into the heating-enabled micellization, leading to a simple and effective process for dye-labeled nanoparticles and drug carriers.
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Serotonin-mediated Modulation of Na+/K+ Pump Current in Rat Hippocampal CA1 Pyramidal Neurons
BMC Neuroscience.
Jan, 2012 |
Pubmed ID: 22257758 ABSTRACT: BACKGROUND: The aim of this study was to investigate whether serotonin (5-hydroxytryptamine, 5-HT) can modulate Na+/K+ pump in rat hippocampal CA1 pyramidal neurons. RESULTS: 5-HT (0.1, 1 mM) showed Na+/K+ pump current (Ip) densities of 0.40+/-0.04, 0.34+/-0.03 pA/pF contrast to 0.63+/-0.04 pA/pF of the control of 0.5 mM strophanthidin (Str), demonstrating 5-HT-induced inhibition of Ip in a dose-dependent manner in hippocampal CA1 pyramidal neurons. The effect was partly attenuated by ondasetron, a 5-HT3 receptor (5-HT3R) antagonist, not by WAY100635, a 5-HT1AR antagonist, while 1-(3-Chlorophenyl) biguanide hydrochloride (m-CPBG), a 5-HT3R specific agonist, mimicked the effect of 5-HT on Ip. CONCLUSION: 5-HT inhibits neuronal Na+/K+ pump activity via 5-HT3R in rat hippocampal CA1 pyramidal neurons. This discloses novel mechanisms for the function of 5-HT in learning and memory, which may be a useful target to benefit these patients with cognitive disorder.
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Inhibition of P38 MAPK Activity Promotes Ex Vivo Expansion of Human Cord Blood Hematopoietic Stem Cells
Annals of Hematology.
Jan, 2012 |
Pubmed ID: 22258328 Ex vivo expansion of hematopoietic stem cells (HSCs) depends on HSC self-renewing proliferation and functional maintenance, which can be negatively affected by HSC differentiation, apoptosis, and senescence. Therefore, inhibition of HSC senescence may promote HSC expansion. To test this hypothesis, we examined the effect of inhibition of p38 mitogen-activated protein kinase (p38) on the expansion of human umbilical cord blood (hUCB) CD133(+) cells because activation of p38 has been implicated in the induction of HSC senescence under various physiological and pathological conditions. Our results showed that ex vivo expansion of hUCB CD133(+) cells activated p38, which was abrogated by the p38 specific inhibitor SB203580 (SB). Inhibition of p38 activity with SB promoted the expansion of CD133(+) cells and CD133(+)CD38(-) cells. In addition, hUCB CD133(+) cells expanded in the presence of SB for 7Â days showed about threefold increase in the clonogenic function of HSCs and engraftment in non-obese diabetic/severe combined immunodeficient mice after transplantation compared to the input cells. In contrast, the cells expanded without SB exhibited a significant reduction in these HSC functions. The enhancement of ex vivo expansion of hUCB HSCs is primarily attributable to SB-mediated inhibition of HSC senescence. In addition, inhibition of HSC apoptosis and upregulation of CXCR4 may also contribute to the enhancement. However, p38 inhibition had no significant effect on HSC differentiation and proliferation. These findings suggest that inhibition of p38 activation may represent a novel strategy to promote ex vivo expansion of hUCB HSCs.
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Elevated Admission Microalbuminuria Predicts Poor Myocardial Blood Flow and 6-Month Mortality in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention
Clinical Cardiology.
Jan, 2012 |
Pubmed ID: 22262165 BACKGROUND: Microalbuminuria (MA) is considered a major risk factor predisposing to cardiovascular morbidity and mortality. Outcomes after percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI) complicated by MA have been well described. However, data regarding admission MA and coronary and myocardial flow are scant. The aims of this study were to evaluate the effects of admission MA on coronary blood flow and prognosis in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. HYPOTHESIS: Did elevated admission microalbuminuria predict poor myocardial blood flow and 6-month mortality in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention? METHODS: A total of 247 patients undergoing primary PCI for STEMI within 12 hours after symptom onset were studied. Patients were divided into 2 groups according to admission urinary albumin extraction rate (UAER): (1) an MA group (UAER 20-200 µg/min), and (2) a normoalbuminuria (NA) group (UAER < 20 µg/min). RESULTS: Microalbuminuria was observed in 108 patients. Univariate analyses showed statistical differences between the NA and MA groups in serum creatine level, plasma glucose level, and peak creatine kinase level on presentation. Thrombolysis In Myocardial Infarction (TIMI) flow grades (TFGs) 0-2 in the MA group were more frequent (9.4% vs 21.2%, P < 0.05) than in the NA group, and corrected TIMI frame count was higher (23.9 ± 18.5 vs 29.8 ± 23.5, P < 0.05). Admission MA was an independent predictor of poor myocardial perfusion (adjusted relative risk: 3.14, 95% confidence interval: 0.99-6.78) and a higher rate of 6-month mortality in STEMI patients undergoing primary PCI (adjusted relative risk: 1.58, 95% confidence interval: 0.74-3.39). CONCLUSIONS: Admission MA levels are associated with impaired myocardial flow and poor prognosis in STEMI patients undergoing primary PCI. © 2012 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.
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Myocardial Perfusion Magnetic Resonance Imaging Using Sliding-Window Conjugate-Gradient Highly Constrained Back-Projection Reconstruction for Detection of Coronary Artery Disease
The American Journal of Cardiology.
Jan, 2012 |
Pubmed ID: 22264595 Myocardial perfusion magnetic resonance imaging (MRI) with sliding-window conjugate-gradient highly constrained back-projection reconstruction (SW-CG-HYPR) allows whole left ventricular coverage, improved temporal and spatial resolution and signal/noise ratio, and reduced cardiac motion-related image artifacts. The accuracy of this technique for detecting coronary artery disease (CAD) has not been determined in a large number of patients. We prospectively evaluated the diagnostic performance of myocardial perfusion MRI with SW-CG-HYPR in patients with suspected CAD. A total of 50 consecutive patients who were scheduled for coronary angiography with suspected CAD underwent myocardial perfusion MRI with SW-CG-HYPR at 3.0 T. The perfusion defects were interpreted qualitatively by 2 blinded observers and were correlated with x-ray angiographic stenoses ≥50%. The prevalence of CAD was 56%. In the per-patient analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SW-CG-HYPR was 96% (95% confidence interval 82% to 100%), 82% (95% confidence interval 60% to 95%), 87% (95% confidence interval 70% to 96%), 95% (95% confidence interval 74% to100%), and 90% (95% confidence interval 82% to 98%), respectively. In the per-vessel analysis, the corresponding values were 98% (95% confidence interval 91% to 100%), 89% (95% confidence interval 80% to 94%), 86% (95% confidence interval 76% to 93%), 99% (95% confidence interval 93% to 100%), and 93% (95% confidence interval 89% to 97%), respectively. In conclusion, myocardial perfusion MRI using SW-CG-HYPR allows whole left ventricular coverage and high resolution and has high diagnostic accuracy in patients with suspected CAD.
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Chemical Characterization of Etched Dentin in Non-Carious Cervical Lesions
The Journal of Adhesive Dentistry.
Jan, 2012 |
Pubmed ID: 22282761 Purpose: Bonding to non-carious cervical lesion (NCCL) sclerotic dentin that involves acid etching continues to be a challenging problem due to its altered chemical structure. In the present study, the objective was to investigate the chemical response of NCCL sclerotic dentin to the different acid etching times. Materials and Methods: Extracted human premolars affected with NCCLs were selected, and a cavity matching the natural lesion with respect to size and location was prepared on the lingual surface of each tooth to serve as the control. The dentin surfaces were treated for 15 s and 30 s using 37% phosphoric acid and then analyzed by Raman microspectroscopic mapping/imaging. Results: NCCL dentin substrates had dramatic effects on the chemical profile of dentin demineralization. The spectral comparison showed that the demineralized layer generated by the acid treatment was highly irregular in terms of depth and mineral component retained, especially when NCCL sclerotic dentin was etched for 15 s. When the etching time was increased to 30 s, the demineralization of NCCL sclerotic dentin was more effective and comparable to the nonsclerotic control that was treated for 15 s. Different etching times affected the depth, degree, and profile of the dentin demineralization. Conclusion: The shorter etching time (ie, 15 s) might not be adequate for NCCL sclerotic dentin. However, the longer etching time (ie, 30 s) would induce much deeper demineralized dentin for nonsclerotic substrates. Thus, although extended etching times can be used to remove the hypermineralized layer, further studies are required to analyze the impact this might have on the dentin bonding.
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AT1 Receptor Blockade Delays Postlactational Mammary Gland Involution: a Novel Role for the Renin Angiotensin System
The FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology.
Jan, 2012 |
Pubmed ID: 22286690 Angiotensin II (AngII), the main effector peptide of the renin-angiotensin system (RAS), participates in multiple biological processes, including cell growth, apoptosis, and tissue remodeling. Since AngII activates, in different cell types, signal transducing pathways that are critical for mammary gland postlactational regression, we investigated the role of the RAS during this process. We found that exogenous administration of AngII in mammary glands of lactating Balb/c mice induced epithelium apoptosis [2.9±0.5% (control) vs. 9.6±1.1% (AngII); P < 0.001] and activation of the proapoptotic factor STAT3, an effect inhibited by irbesartan, an AT(1) receptor blocker. Subsequently, we studied the expression kinetics of RAS components during involution. We found that angiotensin-converting enzyme (ACE) mRNA expression peaked 6 h after weaning (5.7-fold; P
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Islet Preconditioning Via Multimodal Microfluidic Modulation of Intermittent Hypoxia
Analytical Chemistry.
Feb, 2012 |
Pubmed ID: 22296179 Simultaneous stimulation of ex vivo pancreatic islets with dynamic oxygen and glucose is a critical technique for studying how hypoxia alters glucose-stimulated response, especially in transplant environments. Standard techniques using a hypoxic chamber cannot provide both oxygen and glucose modulations, while monitoring stimulus-secretion coupling factors in real-time. Using novel microfluidic device with integrated glucose and oxygen modulations, we quantified hypoxic impairment of islet response by calcium influx, mitochondrial potentials, and insulin secretion. Glucose-induced calcium response magnitude and phase were suppressed by hypoxia, while mitochondrial hyperpolarization and insulin secretion decreased in coordination. More importantly, hypoxic response was improved by preconditioning islets to intermittent hypoxia (IH, 1 min/1 min 5-21% cycling for 1 h), translating to improved insulin secretion. Moreover, blocking mitochondrial K(ATP) channels removed preconditioning benefits of IH, similar to mechanisms in preconditioned cardiomyocytes. Additionally, the multimodal device can be applied to a variety of dynamic oxygen-metabolic studies in other ex vivo tissues.
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A Novel Sulfonamide Agent, MPSP-001, Exhibits Potent Activity Against Human Cancer Cells in Vitro Through Disruption of Microtubule
Acta Pharmacologica Sinica.
Feb, 2012 |
Pubmed ID: 22301862 Aim:To evaluate the anti-cancer effects of a new sulfonamide derivative, 2-(N-(3-chlorophenyl)-4-methoxyphenylsulfonamido)-N-hydroxypropanamide (MPSP-001).Methods:Human cancer cell lines (HepG2, THP-1, K562, HGC-27, SKOV3, PANC-1, SW480, Kba, HeLa, A549, MDA-MB-453, and MCF-7) were examined. The cytotoxicity of MPSP-001 was evaluated using the WST-8 assay. Cell cycle distribution was examined with flow cytometry. Mitotic spindle formation was detected using immunofluorescence microscopy. Apoptosis-related proteins were examined with Western blot using specific phosphorylated protein antibodies. Competitive tubulin-binding assay was performed to test whether the compound competitively bound to the colchicine site. Molecular docking was performed to explore the possible binding conformation.Results:MPSP-001 potently inhibited the growth of the 12 different types of human cancer cells with the IC(50) values ranging from 1.9 to 15.7 μmol/L. The compound exerted potent inhibition on the drug-resistant Kb/VCR and MCF-7/ADR cells, as on Kba and MCF-7 cells. In HeLa, HGC-27, A549, and other cells, the compound (5 μmol/L) caused cell cycle arrest at the G(2)/M phase, and subsequently induced cell apoptosis. In Hela cells, it prevented the mitotic spindle formation. Furthermore, the compound dose-dependently inhibited polymerization of tubulin in vitro, and directly bound to the colchicine-site of β-tubulin. Molecular docking predicted that the compound may form two hydrogen bonds to the binding pocket. The compound showed synergistic effects with colchicine and taxol in blocking mitosis of HeLa cells.Conclusion:MPSP-001 shows a broad-spectrum of anti-tumor efficacy in vitro and represents a novel structure with anti-microtubule activity.
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Improvement in T-Staging of Rectal Carcinoma: Using a Novel Endorectal Ultrasonography Technique with Sterile Coupling Gel Filling the Rectum
Ultrasound in Medicine & Biology.
Feb, 2012 |
Pubmed ID: 22305079 Our purpose was to study the accuracy of using endorectal ultrasonography (ERUS) with sterile coupling gels filling the rectum in the preoperative T-staging of rectal carcinoma. A total of 189 patients with confirmed rectal carcinoma were recruited. All underwent ERUS and surgery within the week following sonography. EURS was performed by introducing sterile coupling gel into the rectum. Two radiologists looked at the images at the same time and agreed upon staging. Rectal carcinoma was staged from Tis to T4. The accuracy of T-staging by ERUS was 89.95%. The sensitivity, specificity, PPV and NPV for ERUS at different stages were calculated. For early stage (Tis and T1), these values were 93.62%, 97.89%, 93.62% and 97.89%, respectively. ERUS filling with sterile coupling gel in the rectum overcomes the pressure effect from a water bath and the restriction caused by tumor stenosis, thus, greatly improving the accuracy of T-staging. The examination is real-time, safe and inexpensive.
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The Distribution of Carbonate in Enamel and Its Correlation with Structure and Mechanical Properties
Journal of Materials Science.
Dec, 2012 |
Pubmed ID: 25221352 The correlation of carbonate content with enamel microstructure (chemical and crystal structure) and mechanical properties was evaluated via linear mapping analyses using Raman microspectroscopy and nanoindentation. Mappings started at the outer enamel surface and ended in the inner enamel near the dentin-enamel junction (DEJ) in lingual and buccal cervical and cuspal regions. The carbonate peak intensity at 1070 cm(-1) gradually increased from outer to inner enamel. Moreover, the phosphate peak width, as measured by the full width at half maximum (FWHM) of the peak at 960 cm(-1), also increased, going from ~9 cm(-1) in outer enamel to ~13 cm(-1) in enamel adjacent to the DEJ, indicating a decrease in the degree of crystallinity of hydroxyapatite from outer to inner enamel. In contrast, Young's modulus decreased from 119±12 to 80±19 GPa across outer to inner enamel with a concomitant decrease in enamel hardness from 5.9±1.4 to 3.5±1.3 GPa. There were also significant correlations between carbonate content and associated crystallinity with mechanical properties. As carbonate content increased, there was an associated decrease in crystallinity and both of these changes correlated with decreased modulus and hardness. Collectively, these results suggest that enamel carbonate content and the associated change in the crystal structure of hydroxyapatite, i.e. degree of crystallinity, may have a direct effect on enamel mechanical properties. The combination of Raman microspectroscopy and nanoindentation proved to be an effective approach for evaluating the microstructure of enamel and its associated properties.
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The Response of Juxtacellular Labeled GABA Interneurons in the Basolateral Amygdaloid Nucleus Anterior Part to 5-HT₂A/₂C Receptor Activation is Decreased in Rats with 6-hydroxydopamine Lesions
Neuropharmacology.
Oct, 2013 |
Pubmed ID: 23827319 Here we report that juxtacellular labeled GABA interneurons in the basolateral amygdaloid nucleus anterior part (BLA) of rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) showed a more burst-firing pattern, while having no change in the firing rate. In sham-operated and the lesioned rats, systemic administration of 5-HT(2A/2C) receptor agonist DOI produced excitation, inhibition and unchanged in the firing rate of the interneurons, and the mean response of DOI was excitatory. However, cumulative dose producing excitation in the lesioned rats was higher than that of sham-operated rats. The local administration of DOI in the BLA also produced three types of responses in two groups of rats. Furthermore, the local administration of DOI excited the interneurons in sham-operated rats, whereas the mean firing rate of the interneurons in the lesioned rats was not affected at the same dose. The excitatory effect of the majority of the interneurons after systemic and local administration of DOI was not reversed by the selective 5-HT(2C) receptor antagonist SB242084, and the inhibitory effect of DOI in all the interneurons examined was reversed by GABA(A) receptor antagonist picrotoxinin. The SNc lesion in rats did not change the density of GAD67/5-HT(2A) receptor co-expressing neurons in the BLA. These results indicate that the SNc lesion changes the firing activity of BLA GABA interneurons. Moreover, DOI regulated the firing activity of the interneurons mainly through activation of 5-HT(2A) receptor, and the lesion led to a decreased response of the interneurons to DOI, which attributes to dysfunction of 5-HT(2A) receptor on these interneurons.
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Interleukin-6 is Overexpressed and Augments Invasiveness of Human Glioma Stem Cells in Vitro
Clinical & Experimental Metastasis.
Jul, 2013 |
Pubmed ID: 23832741 In the present study, we carried out a series of assays to investigate the expression of interleukin-6 in glioma stem cells and its role in glioma stem cells invasion. Glioma stem cells from eight surgical glioma specimens were cultured and identified. Real-time reverse transcription polymerase chain reaction and immunoassay were used to measure and compare the expression levels of interleukin-6 in glioma stem cells and matched primary glioma cells. Subsequently, neutralizing antibody against interleukin-6 or exogenous interleukin-6 was used in a Matrigel-invasion assay and effects of interleukin-6 on glioma stem cells invasiveness was then determined. The results revealed that interleukin-6 mRNA and protein expression levels were significantly higher in glioma stem cells than in primary glioma cells from the same tumor. However, its expression levels were not apparently higher in glioma stem cells from grade IV gliomas than from grade III gliomas. In Matrigel-invasion assay, glioma stem cells invasiveness markedly decreased after interleukin-6 was blocked with neutralizing antibody, but significantly increased when exogenous interleukin-6 was added. Additionally, the similar effects of interleukin-6 were also found on primary glioma cells invasiveness. Our results suggest that glioma stem cells are likely to be the major tumor source of immunosuppressive cytokines interleukin-6 and thereby play a crucial role in determining glioma malignancy, immunosuppression and immune evasion. Furthermore, interleukin-6 can significantly augment glioma stem cells invasiveness in vitro, suggesting a potential target in future therapy for glioma stem cells rather than for their derivatives.
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Risk Factors for Infectious Diseases in Backyard Poultry Farms in the Poyang Lake Area, China
PloS One.
2013 |
Pubmed ID: 23840680 Emergence and transmission of infectious diseases have an enormous impact on the poultry industry and present a serious threat to the health of humans and wild birds. Noncommercial poultry operations, such as backyard poultry facilities in China, are potential sources of virus exchange between commercial poultry and wild birds. It is particularly critical in wetland areas where backyard poultry have close contact with commercial poultry and migratory birds, therefore increasing the risk of contracting infectious diseases. To evaluate the transmission risks, a cross-sectional study was undertaken in the Poyang Lake area, China, involving 309 residents in the backyard poultry farms in three counties (Region A, B, and C) of Jiangxi Province. We examined the backyard poultry population, poultry species, presence of poultry deaths from infectious diseases, food sources, and biosecurity practices. Region B ranked highest for biosecurity while region C ranked lowest. The risks of infectious diseases were assessed by adjusted odds ratio based on multivariate logistic regression analysis. Potential risk factors in the three regions of the study site were compared. In Region A, significant factor was contact of poultry with wild birds (OR: 6.573, 95% CI: 2.148-20.115, P=0.001). In Region B, the most significant factor was contact of poultry with neighboring backyard waterfowls (OR: 3.967, 95% CI: 1.555-10.122, P=0.004). In Region C, significant factors were poultry purchase from local live bird markets (OR: 3.740, 95% CI: 1.243-11.255, P=0.019), and contact of poultry with wild birds (OR: 3.379, 95% CI: 1.058-10.791, P=0.040). In summary, backyard poultry was significantly affected by neighboring commercial poultry and close contact with wild birds. The results are expected to improve our understanding of the transmission risks of infectious diseases in a typical backyard poultry environment in rural China, and address the need to improve local farming practices and take preventive measures.
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Avastin Exhibits Therapeutic Effects on Collagen-induced Arthritis in Rat Model
Inflammation.
Dec, 2013 |
Pubmed ID: 23851616 Avastin is the monoclonal antibody for vascular endothelial growth factor (VEGF). This study aimed to investigate therapeutic effect of Avastin on type II collagen-induced arthritis. Type II chicken collagen was injected into the tails of Wistar rats, and 60 modeled female rats were randomly divided into three groups (n = 20): Avastin group, Etanercept group, and control group. Arthritis index and joint pad thickness were scored, and the pathology of back metapedes was analyzed. The results showed that compared to control group, the arthritis index, target-to-non-target ratio, synovial pathological injury index, serum levels of VEGF and tumor necrosis factor alpha, and VEGF staining were decreased significantly 14 days after Avastin or Etanercept treatment, but there were no significant differences between Avastin group and Etanercept group. These data provide evidence that Avastin exhibits similar effects to Etanercept to relieve rheumatoid arthritis in rat model and suggest that Avastin is a promising therapeutic agent for rheumatoid arthritis.
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QSYQ Attenuates Oxidative Stress and Apoptosis Induced Heart Remodeling Rats Through Different Subtypes of NADPH-Oxidase
Evidence-based Complementary and Alternative Medicine : ECAM.
2013 |
Pubmed ID: 23861715 We aim to investigate the therapeutic effects of QSYQ, a drug of heart failure (HF) in clinical practice in China, on a rat heart failure (HF) model. 3 groups were divided: HF model group (LAD ligation), QSYQ group (LAD ligation and treated with QSYQ), and sham-operated group. After 4 weeks, rats were sacrificed for cardiac injury measurements. Rats with HF showed obvious histological changes including necrosis and inflammation foci, elevated ventricular remodeling markers levels(matrix metalloproteinases-2, MMP-2), deregulated ejection fraction (EF) value, increased formation of oxidative stress (Malondialdehyde, MDA), and up-regulated levels of apoptotic cells (caspase-3, p53 and tunnel) in myocardial tissue. Treatment of QSYQ improved cardiac remodeling through counter-acting those events. The improvement of QSYQ was accompanied with a restoration of NADPH oxidase 4 (NOX4) and NADPH oxidase 2 (NOX2) pathways in different patterns. Administration of QSYQ could attenuate LAD-induced HF, and AngII-NOX2-ROS-MMPs pathway seemed to be the critical potential targets for QSYQ to reduce the remodeling. Moreover, NOX4 was another key targets to inhibit the p53 and Caspase3, thus to reduce the hypertrophy and apoptosis, and eventually provide a synergetic cardiac protective effect.
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Enhancing Isoprenoid Production Through Systematically Assembling and Modulating Efflux Pumps in Escherichia Coli
Applied Microbiology and Biotechnology.
Sep, 2013 |
Pubmed ID: 23864262 Enhancement of the cellular exportation of heterologous compounds is an important aspect to improve the product yield in microbial cell factory. Efflux pumps can expel various intra- or extra-cellular substances out of microbial hosts and increase the cellular tolerance. Thus in this study, by using the hydrophobic sesquiterpene (amorphadiene) and diterpene (kaurene) as two model compounds, we attempted to improve isoprenoid production through systematically engineering the efflux pumps in Escherichia coli BL21(DE3). The pleiotropic resistant pumps, AcrAB-TolC, MdtEF-TolC from E. coli and heterologous MexAB-OprM pump from Pseudomonas aeruginosa, were overexpressed, assembled, and finely modulated. We found that overexpression of AcrB and TolC components can effectively enhance the specific yield of amorphadiene and kaurene, e.g., 31 and 37 % improvement for amorphadiene compared with control, respectively. The heterologous MexB component can enhance kaurene production with 70 % improvement which is more effective than TolC and AcrB. The results suggest that the three components of tripartite efflux pumps play varied effect to enhance isoprenoid production. Considering the highly organized structure of efflux pumps and importance of components interaction, various component combinations were constructed and the copy number of key components AcrB and TolC was finely modulated as well. The results exhibit that the combination TolC and TolC and AcrB improved the specific yield of amorphadiene with 118 %, and AcrA and TolC and AcrB improved that of kaurene with 104 %. This study indicates that assembling and finely modulating efflux pumps is an effective strategy to improve the production of heterologous compounds in E. coli.
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A Novel High-pressure Precipitation Tandem Homogenization Technology for Drug Nanocrystals Production - a Case Study with Ursodeoxycholic Acid
Pharmaceutical Development and Technology.
Jul, 2013 |
Pubmed ID: 23869484 Abstract To overcome the limitations of the conventional particle size reduction technologies, a novel combinative particle size reduction method for the effective production of homogeneous nanosuspensions was investigated. Ursodeoxycholic acid, a poorly soluble drug representative, was tried to prepare nanosuspension by homogenization technology and high-pressure precipitation tandem homogenization technology. It was shown that the combinative approach could significantly improve the particle size reduction effectiveness over conventional homogenization approach. The Box-Behnken design analysis for process optimization revealed that the acceptable UDCA-NS was obtained wherein the optimal values of A, B, C and D were 10%, 500 bar, 0.125 and 600 bar, respectively. SEM results demonstrated that no significant aggregation or crystals growth could be observed in the freeze-dried UDCA nanocrystals. The DSC and XRD results showed that UDCA remained in a crystalline state. Dissolution velocities of the freeze-dried UDCA-NS powder were distinctly superior compared to those of the crude powder and physical mixture. The high-pressure precipitation tandem homogenization technology can be a good choice for nanosuspension preparation of poorly soluble UDCA, due to high efficiency of particle size reduction.
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Spatio-temporal Analysis of Type 2 Diabetes Mellitus Based on Differential Expression Networks
Scientific Reports.
2013 |
Pubmed ID: 23881262 T2DM is complex in its dynamical dependence on multiple tissues, disease states, and factors' interactions. However, most existing work devoted to characterizing its pathophysiology from one static tissue, individual factors, or single state. Here we perform a spatio-temporal analysis on T2DM by developing a new form of molecular network, i.e. 'differential expression network' (DEN), which can reflect phenotype differences at network level. Static DENs show that three tissues (white adipose, skeletal muscle, and liver) all suffer from severe inflammation and perturbed metabolism, among which metabolic functions are seriously affected in liver. Dynamical analysis on DENs reveals metabolic function changes in adipose and liver are consistent with insulin resistance (IR) deterioration. Close investigation on IR pathway identifies 'disease interactions', revealing that IR deterioration is earlier than that on SlC2A4 in adipose and muscle. Our analysis also provides evidence that rising of insulin secretion is the root cause of IR in diabetes.
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Recombinant Human Sonic Hedgehog Protein Regulates the Expression of ZO-1 and Occludin by Activating Angiopoietin-1 in Stroke Damage
PloS One.
2013 |
Pubmed ID: 23894369 This study examines the regulating effect of Sonic Hedgehog (Shh) on the permeability of the blood-brain barrier (BBB) in cerebral ischemia. By employing permanent middle cerebral artery occlusion (pMCAO) model, we find that Shh significantly decreases brain edema and preserves BBB permeability. Moreover, Shh increases zonula occludens-1 (ZO-1), occludin and angiopiotetin-1 (Ang-1) expression in the ischemic penumbra. Blockage of Shh with cyclopamine abolishes the effects of Shh on brain edema, BBB permeability and ZO-1, occludin, Ang-1 expression. Primary brain microvessel endothelial cells (BMECs) and astrocytes were pre-treated with Shh, cyclopamine, Ang-1-neutralizing antibody, and subjected to oxygen-glucose deprivation (OGD). Results show that the Ang-1 protein level in the culture medium of Shh-treated astrocytes is significantly higher. Shh also increased ZO-1, occludin and Ang-1 expression in BMECs, while cyclopamine and Ang-1-neutralizing antibody inhibited the effects of Shh on the ZO-1 and occludin expression, respectively. This study suggests that, under ischemic insults, Shh triggers Ang-1 production predominantly in astrocytes, and the secreted Ang-1 acts on BMECs, thereby upregulating ZO-1 and occludin to repair the tight junction and ameliorate the brain edema and BBB leakage.
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Immune Responses in Mice Vaccinated with a Suicidal DNA Vaccine Expressing the Hemagglutinin Glycoprotein from the Peste Des Petits Ruminants Virus
Journal of Virological Methods.
Nov, 2013 |
Pubmed ID: 23896018 Peste des petits ruminants (PPR), an acute and highly contagious disease, affects sheep, goats, and some small ruminants. The hemagglutinin (H) glycoprotein of the PPR virus (PPRV) is considered important for inducing protective immune responses. In this study, a suicidal DNA vaccine based on the Semliki Forest virus (SFV) replicon was constructed and tested for its ability to induce immunogenicity in a mouse model. For this, the H gene of PPRV was cloned and inserted into pSCA1, an SFV replicon vector. The resultant plasmid named pSCA1-H was then transfected into BHK-21 cells following which the antigenicity of the expressed protein was confirmed by Western blotting and immunofluorescence. The pSCA1-H plasmid was then injected intramuscularly into BALB/c mice thrice at 2-week intervals. To evaluate the immunogenicity of pSCA1-H, specific antibodies and neutralizing antibodies against PPRV-H were measured using an indirect enzyme-linked immunosorbent assay and a microneutralization test, respectively. Cell-mediated immune responses were also examined using a lymphocyte proliferation assay. The results showed that pSCA1-H could express the H protein in BHK-21 cells. Specific antibodies, neutralizing antibodies, and lymphocyte proliferation responses were all induced in mice. Thus, this suicidal DNA vaccine could be a promising new approach for vaccine development against PPR.
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[Effects of Different Tillage and Fertilization Modes on the Soil Physical and Chemical Properties and Crop Yield Under Winter Wheat/spring Corn Rotation on Dryland of East Gansu, Northwest China]
Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban.
Apr, 2013 |
Pubmed ID: 23898658 Based on the 7-year field experiment on the dryland of east Gansu of Northwest China in 2005-2011, this paper analyzed the variations of soil moisture content, bulk density, and nutrients content at harvest time of winter wheat and of the grain yield under no-tillage and conventional tillage and five fertilization modes, and approached the effects of different tillage and fertilization modes on the soil water storage and conservation, soil fertility, and grain yield under winter wheat/ spring corn rotation. In 2011, the soil moisture content in 0-200 cm layer and the soil bulk density and soil organic matter and available nitrogen and phosphorus contents in 0-20 cm and 20-40 cm layers under different fertilization modes were higher under no-tillage than under conventional tillage. Under the same tillage modes, the contents of soil organic matter and available nitrogen and available phosphorus were higher under the combined application of organic and inorganic fertilizers, as compared with other fertilization modes. The soil available potassium content under different tillage and fertilization modes decreased with years. The grain yield under conventional tillage was higher than that under no-tillage. Under the same tillage modes, the grain yield was the highest under the combined application of organic and inorganic fertilizers, and the lowest under no fertilization. In sum, no-tillage had the superiority than conventional tillage in improving the soil water storage and conservation and soil fertility, and the combined application of organic and inorganic fertilizers under conventional tillage could obtain the best grain yield.
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Hydroxyapatite Induces Spontaneous Polymerization of Model Self-etch Dental Adhesives
Materials Science & Engineering. C, Materials for Biological Applications.
Oct, 2013 |
Pubmed ID: 23910263 The objective of this study is to report for the first time the spontaneous polymerization phenomenon of self-etch dental adhesives induced by hydroxylapatite (HAp). Model self-etch adhesives were prepared by using a monomer mixture of bis[2-(methacryloyloxy)ethyl] phosphate (2MP) with 2-hydroxyethyl methacrylate (HEMA). The initiator system consisted of camphorquinone (CQ, 0.022 mmol/g) and ethyl 4-dimethylaminobenzoate (4E, 0.022-0.088 mmol/g). HAp (2-8 wt.%) was added to the neat model adhesive. In a dark environment, the polymerization was monitored in-situ using ATR/FT-IR, and the mechanical properties of the polymerized adhesives were evaluated using nanoindentation technique. Results indicated that spontaneous polymerization was not observed in the absence of HAp. However, as different amounts of HAp were incorporated into the adhesives, spontaneous polymerization was induced. Higher HAp content led to higher degree of conversion (DC), higher rate of polymerization (RP) and shorter induction period (IP). In addition, higher 4E content also elevated DC and RP and reduced IP of the adhesives. Nanoindentation result suggested that the Young's modulus of the polymerized adhesives showed similar dependence on HAp and 4E contents. In summary, interaction with HAp could induce spontaneous polymerization of the model self-etch adhesives. This result provides important information for understanding the initiation mechanism of the self-etch adhesives, and may be of clinical significance to strengthen the adhesive/dentin interface based on the finding.
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Multicondition Optimization and Experimental Measurements of a Double-Blade Centrifugal Pump Impeller
Journal of Fluids Engineering.
Jan, 2013 |
Pubmed ID: 23917426 In order to improve internal unsteady flow in a double-blade centrifugal pump (DBCP), this study used major geometric parameters of the original design as the initial values, heads at three conditions (i.e., 80% design flow rate, 100% design flow rate, and 120% design flow rate) as the constraints conditions, and the maximum of weighted average efficiency at the three conditions as the objective function. An adaptive simulated annealing algorithm was selected to solve the energy performance calculation model and the supertransitive approximation method was applied to fix optimal weight factors of individual objectives. On the basis of hydraulic performance optimization, three-condition automatic computational fluid dynamics (CFD) optimization of impeller meridional plane for the DBCP was realized by means of Isight software integrated Pro/E, Gambit, and Fluent software. The shroud arc radii R0 and R1, shroud angle T1, hub arc radius R2, and hub angle T2 on the meridional plane were selected as the design variables and the maximum of weighted average hydraulic efficiency at the three conditions was chosen as the objective function. Performance characteristic test and particle image velocimetry (PIV) measurements of internal flow in the DBCP were conducted. Performance characteristic test results show that the weighted average efficiency of the impeller after the three-condition optimization has increased by 1.46% than that of original design. PIV measurements results show that vortex or recirculation phenomena in the impeller are distinctly improved under the three conditions.
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Comparative Messenger RNA Expression of FSHβ, LHβ, FSHR, LHR, and ERβ in High and Low Prolific Goat Breeds
Animal Biotechnology.
2013 |
Pubmed ID: 23947667 Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) have a central role in follicle growth and maturation, but no clear differences between breeds with different ovulation rates have been found. Therefore, this study investigated mRNA expression of FSHβ, LHβ, FSH receptor (FSHR), LH receptor (LHR), and estrogen receptor-β (ERβ) genes in prolific Lezhi black (LB) goats and nonprolific Tibetan (TB) goats by real-time PCR. Follicles and pituitaries were recovered from goats at 12-24 h after onset of estrus. Real-time PCR analysis revealed that the expression levels of FSHβ and LHβ mRNA were significantly higher (p < 0.01) in pituitary of LB than in TB does, but the expression levels of FSHR and LHR mRNA in follicle of TB were greater (p < 0.05). Expression level of follicular ER β was not different between the two breeds. Data provide evidence that the greater ovulation rate in the LB goat as compared to the TB breed is associated with a greater gonadotropin expression during follicular phase.
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Shape-controlled Synthesis of Hollow Silica Colloids
Langmuir : the ACS Journal of Surfaces and Colloids.
Sep, 2013 |
Pubmed ID: 23957469 In this work, hollow silica colloids with different shapes, such as pseudocubes, ellipsoids, capsules, and peanuts, have been synthesized through the following process: silica coating on the surface of hematite colloidal particles with different shapes (pseudocubes, ellipsoids, capsules, and peanuts) and the sequential acid dissolution of the hematite cores. The as-obtained hollow silica colloids with different shapes have uniform sizes, shapes, and shells.
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Subunit Vaccine Consisting of Multi-stage Antigens Has High Protective Efficacy Against Mycobacterium Tuberculosis Infection in Mice
PloS One.
2013 |
Pubmed ID: 23967337 To search for more effective tuberculosis (TB) subunit vaccines, antigens expressed in different growth stages of Mycobacterium tuberculosis (M. tuberculosis), such as RpfE (Rv2450c) produced in the stage of resuscitation, Mtb10.4 (Rv0288), Mtb8.4 (Rv1174c), ESAT6 (Rv3875), Ag85B (Rv1886c) mainly secreted by replicating bacilli, and HspX (Rv2031c) highly expressed in dormant bacilli, were selected to construct six fusion proteins: ESAT6-Ag85B-MPT64190-198-Mtb8.4 (EAMM), Mtb10.4-HspX (MH), ESAT6-Mtb8.4, Mtb10.4-Ag85B, ESAT6-Ag85B, and ESAT6-RpfE. The six fusion proteins were separately emulsified in an adjuvant composed of N,N'-dimethyl-N, N'-dioctadecylammonium bromide (DDA), polyribocytidylic acid (poly I:C) and gelatin to construct subunit vaccines, and their protective effects against M. tuberculosis infection were evaluated in C57BL/6 mice. Furthermore, the boosting effects of EAMM and MH in the adjuvant of DDA plus trehalose 6,6'-dimycolate (TDM) on BCG-induced immunity were also evaluated. It was found that the six proteins were stably produced in E. coli and successfully purified by chromatography. Among them, EAMM presented the most effective protection against M. tuberculosis. Interestingly, the mice that received EAMM+MH had significantly lower bacterial counts in the lungs and spleens than the single protein vaccinated groups, and had the same effect as those that received BCG. In addition, EAMM and MH could improve BCG-primed protective efficacy against M. tuberculosis infection in mice. In conclusion, the combination of EAMM and MH containing antigens from both replicating and dormant stages of the bacilli could induce robust immunity against M. tuberculosis infection in mice and may serve as promising subunit vaccine candidate.
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MiR-335 Suppresses Migration and Invasion by Targeting ROCK1 in Osteosarcoma Cells
Molecular and Cellular Biochemistry.
Dec, 2013 |
Pubmed ID: 23975506 Accumulating evidence has shown that microRNAs are involved in multiple processes in cancer development and progression. Recently, miR-335 has been identified as a tumor-suppressing microRNA in many human cancers. However, the specific function of miR-335 in osteosarcoma is unclear at this point. In this study, we found that the expression of miR-335 in osteosarcoma tissues and cell lines was much lower than that in normal control, respectively, and the downregulated miR-335 was significantly associated with lymph-node metastasis. Transfection of miR-335 mimics could significantly inhibit the cell migration and invasion in MG-63 and U2OS osteosarcoma cell lines. Moreover, we also showed that ROCK1 was negatively regulated by miR-335 at the posttranscriptional level, via a specific target site within the 3'UTR by luciferase reporter assay. The expression of ROCK1 was inversely correlated with miR-335 expression in osteosarcoma tissues, and knockdown of ROCK1 by siRNA-inhibited osteosarcoma cells migration and invasion resembling that of miR-335 overexpression. Thus, our findings suggest that miR-335 acts as tumor suppressor by targeting the ROCK1 gene and inhibiting osteosarcoma cells migration and invasion. The findings of this study contribute to current understanding of the functions of miR-335 in osteosarcoma.
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Functional Characterization of Autographa Californica Multiple Nucleopolyhedrovirus ORF43 and Phenotypic Changes of ORF43-knockout Mutant
Journal of Microbiology (Seoul, Korea).
Aug, 2013 |
Pubmed ID: 23990304 ORF43 (ac43) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is a highly conserved baculovirus gene of unknown function. To investigate the role of ac43 in the baculovirus lifecycle, we constructed an ac43-deleted mutant AcMNPV, Ac43KO. After transfection into Spodoptera frugiperda cells, Ac43KO produced polyhedra much larger in size than those of wild-type AcMNPV. Interestingly, some of the nucleocapsids were singly enveloped in the polyhedrin matrix while the nucleocapsids of AcMNPV are known to be multiply enveloped. Furthermore, Ac43KO led to a defect in the transcription and expression of polyhedrin, which resulted in reduced occlusion body production. However, Ac43KO did not affect production of budded virus as there was no remarkable difference in budded virus titer. These results suggest that ac43 plays an important role in the expression of polyhedrin, the morphogenesis of occlusion body, and the assembly of virions occluded in occlusion bodies.
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[Clinical and Experimental Characteristics of 20 Patients with Acute Myeloid Leukemia with Complex Variant of T(8; 21)]
Zhongguo Shi Yan Xue Ye Xue Za Zhi / Zhongguo Bing Li Sheng Li Xue Hui = Journal of Experimental Hematology / Chinese Association of Pathophysiology.
Jul, 2013 |
Pubmed ID: 23998566 This study was aimed to summarize and analyze the morphology, immunophenotype, cytogenetics, molecular biology (MICM), tyrosine kinase (TK) gene mutations and clinical features of acute myeloid leukemia(AML) with complex variant of t(8;21). A retrospective study was performed for 20 AML patients with complex variant of t(8;21) in our hospital from January 1994 to April 2012, including analysis of clinical feature, immunophenotype, chromosome karyotype, treatment regimen, as well as the overall survival (OS) and relapse-free survival (RFS). Mutations of C-KIT, FLT3-ITD, FLT3-TKD and JAK2V617F were detected by genomic DNA PCR and the sequencing was per-formed in 13 AML patients with complex variant of t(8;21). The results showed that (1) the incidence of 20 AML patietns with complex variant of t(8; 21) was 2.4% of total t(8; 21) AML patients. In 20 AML patients with complex variant of t(8;21), 1 case was M1, 17 cases were M2, 2 cases were M4; 10 cases were myeloid phenotype and the other 3 were myeloid plus lymphoid phenotype. There were 16 kinds of cytogenetics additional involvement of chromosomal breakpoints: lp22, 1p32, 2q35, 2q14, 3p25, 5q13, 6p22, 7q21, llq11, 1lq13, 12q14, 12q24, 12p12, 14q32, 15p13, 20q12. (2) C-KIT aberrations were detected in 30.8% cases, all mutated in exon 17 (mutkit 17), only 1 case had JAK2V617F mutation. The result of FLT3 mutation screenings in AML patients with complex variant of t(8; 21) was negative. Of 5 patients with gene mutations, 1 patient (20%) achieved complete remission (CR), the median RFS and median OS time were 6.5 months and 8.9 months respectively. Of the 8 patients without gene mutations, 6 patietns (75%) achieved CR; the median RFS and median OS time were 26.6 months and 27.7 months respectively. It is concluded that the AML patients with complex variant of t(8;21) shows typical features of t(8;21) AML, but the existence of the tyrosine kinase-related gene mutation has important implications on remission rate and long-term survival of patients treated by induction chemotherapy.
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Combination of SiRNA-directed Kras Oncogene Silencing and Arsenic-induced Apoptosis Using a Nanomedicine Strategy for the Effective Treatment of Pancreatic Cancer
Nanomedicine : Nanotechnology, Biology, and Medicine.
Sep, 2013 |
Pubmed ID: 24028894 The synergetic inhibitory effects on human pancreatic cancer by nanoparticle-mediated siRNA and arsenic therapy were investigated both in vitro and in vivo. Poly(ethylene glycol)-block-poly(l-lysine) were prepared to form siRNA-complexed polyplex and poly(ethylene glycol)-block-poly(dl-lactide) were prepared to form arsenic-encapsulated vesicle, respectively. Down-regulation of the mutant Kras gene by siRNA caused defective abilities of proliferation, clonal formation, migration, and invasion of pancreatic cancer cells, as well as cell cycle arrest at the G0/G1 phase, which substantially enhanced the apoptosis-inducing effect of arsenic administration. Consequently, co-administration of the two nanomedicines encapsulating siRNA or arsenic showed ideal tumor growth inhibition both in vitro and in vivo as a result of synergistic effect of the siRNA-directed Kras oncogene silencing and arsenic-induced cell apoptosis. These results suggest that the combination of mutant Kras gene silencing and arsenic therapy using nanoparticle-mediated delivery strategy is promising for pancreatic cancer treatment.
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Synthesis of Glycyrrhetinic Acid-modified Chitosan 5-fluorouracil Nanoparticles and Its Inhibition of Liver Cancer Characteristics in Vitro and in Vivo
Marine Drugs.
2013 |
Pubmed ID: 24048270 Nanoparticle drug delivery (NDDS) is a novel system in which the drugs are delivered to the site of action by small particles in the nanometer range. Natural or synthetic polymers are used as vectors in NDDS, as they provide targeted, sustained release and biodegradability. Here, we used the chitosan and hepatoma cell-specific binding molecule, glycyrrhetinic acid (GA), to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by Fourier transformed infrared spectroscopy (FT-IR) and ¹H-nuclear magnetic resonance (¹H-NMR). By combining GA-CTS and 5-FU (5-fluorouracil), we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 217.2 nm, a drug loading of 1.56% and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained release system comprising three distinct phases of quick, steady and slow release. We demonstrated that the nanoparticle accumulated in the liver. In vitro data indicated that it had a dose- and time-dependent anti-cancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. Additionally, GA-CTS/5-FU significantly inhibited the growth of drug-resistant hepatoma, which may compensate for the drug-resistance of 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited tumor growth, resulting in increased survival time.
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Enzymatic Hydrolysis Preparation of Mono-O-lauroylsucrose Via a Mono-O-lauroylraffinose Intermediate
Journal of Agricultural and Food Chemistry.
Sep, 2013 |
Pubmed ID: 24050752 1'-O-Lauroylsucrose and 6'-O-lauroylsucrose were formed through hydrolysis of the C-6″ galactose group of 1'-O-lauroylraffinose and 6'-O-lauroylraffinose, respectively, in the presence of α-galactosidase. The enzymatic hydrolysis of 1'-O-lauroylraffinose and 6'-O-lauroylraffinose is discussed in detail. Acetic acid-sodium acetate was chosen as the buffer solution of the enzymatic hydrolysis reaction. The optimum conditions for the enzymatic hydrolysis reaction were as follows: buffer solution, pH 3.8; enzymatic time, 48 h; and enzymatic temperature, 37 °C. Under the optimal process conditions, the efficiency of α-galactosidase was ca. 82.6%. The isomers were fully compared in solubility, hydrophile-lipophile balance (HLB) values, critical micelle concentration (CMC), and thermal stability. The results showed that all lauroylsucrose isomers have similar solubilities in polar solvent, HLB values, CMC values, and thermal stabilities.
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Pulmonary Arterial Hypertension and MicroRNAs-An Ever-growing Partnership
Archives of Medical Research.
Oct, 2013 |
Pubmed ID: 24051036 Pulmonary arterial hypertension (PAH) is a debilitating condition with progressive remodeling of the pulmonary resistance vessels. PAH is characterized by multifocal, polyclonal lesions inhabited by cells that underwent phenotypic transition, resulting in altered cell proliferation and contractility, ultimately resulting in increased vascular resistance. Diagnosis of PAH is confounded by the fact that it is largely asymptomatic in the initial stages. In fact, idiopathic PAH patients >65 years of age cannot be diagnosed hemodynamically due to high pulmonary capillary wedge pressure. This highlights the need for defining more robust molecular biomarkers for PAH diagnosis and progression. Recent studies have indicated that microRNAs (miRNAs), a class of small noncoding RNAs that regulate gene expression, play a discrete role in vascular inflammation and in the etiology of cardiovascular pathologies inclusive of PAH and can potentially serve as diagnostic biomarkers. However, a cohesive understanding of global miRNA-mediated molecular events that control pulmonary vasculature plasticity is lacking which, if addressed systematically, can lead to detailed elucidation of the downstream cellular pathways that are affected by activation/silencing of silenced cognate transcripts. In turn, this can lead to not only robust biomarkers, but also to novel therapeutic strategies targeting more upstream regulators than the existing ones targeting more downstream effectors. The current review aims to provide a summary understanding of PAH, its associated pathophysiology, current knowledge of the role of miRNAs in PAH, and identifies grey areas that need further research for successful bench-to-bedside transition of these exciting new discoveries.
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[Characterization of Stability of Polypeptides and Glycoproteins by Capillary Electrophoresis]
Se Pu = Chinese Journal of Chromatography / Zhongguo Hua Xue Hui.
Jun, 2013 |
Pubmed ID: 24063193 A capillary electrophoresis (CE) method was developed for the stability characterization of polypeptides and glycoproteins. Angiotensin II (Ang II), phytagglutinin (PHA), bovine thrombin (B-Thr), human thrombin (H-Thr) and horseradish peroxidase (HRP) were used as polypeptide and glycoprotein mode molecules. The parameters affecting the analysis efficiency for Ang II, such as sample concentration, running buffer, pH and ionic strength of sample solution were optimized, as for the glycoprotein, capillary conditions, charge state of sample, running buffer and applied voltage were optimized. It showed that the Ang II was stable when kept in borate buffer (0.02 mol/L pH 7.4) at 4 degrees C for 48 h. The four glycoproteins were quite stable in borate buffer (0.2 mol/L pH 7.4) at 20, 4, -20 degrees C for 48 h, and also kept stable at - 20 degrees C when deposited over one week and less than four weeks. HRP was the only one that kept stable when deposited over two weeks and less than four weeks. This method is effective, rapid, simple and low-cost and can be widely used for the stability characterization of polypeptides and glycoproteins.
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Upregulation of TRPC1 Contributes to Contractile Function in Isoproterenol-induced Hypertrophic Myocardium of Rat
Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology.
2013 |
Pubmed ID: 24107839 Aims: The transient receptor potential canonical channel 1 (TRPC1) is a crucial component of the stretch-activated ion channels (SACs). The objective of this research was to demonstrate the contribution of TRPC1 in maintaining cardiac contractile function in the hypertrophic myocardium. Methods: Hypertrophic rat hearts were induced by injecting isoproterenol intraperitoneally, and the expressions of TRPC1/3/6 and Na(+)/Ca(2+) exchanger 1 (NCX1) proteins were analyzed by Western blot. The intracellular calcium images, the action potential of myocardium, the length-dependent contractile force of ventricle muscle and the cardiac output of isolated heart were investigated. Results: The expression of TRPC1 was increased in the hypertrophic myocardium. After being stretched, the ascendant amplitude of the increase in the intracellular calcium ion concentration ([Ca(2+)]i) in the hypertrophic myocardium was higher than that in the normal myocardium. The increase of the APD50 and the amplitude of the membrane potential depolarization were more significant in the hypertrophic myocardium after the activation of SACs. When the heart preparations were perfused with Tyrode's solution, there was no difference in the cardiac systolic function between the cardiac hypertrophy group and the control group. Gadolinium, a SACs blocker, reduced the length-dependent contractile force and suppressed the ascending limb of the Frank-Starling curves in the hypertrophic heart. Conclusions: The upregulation of TRPC1 contributes to the contractile function in the hypertrophic myocardium by increasing [Ca(2+)]i through the SACs. © 2013 S. Karger AG, Basel.
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Integrated Proteomic and Metabolomic Analysis Reveals the NADH-mediated TCA Cycle and Energy Metabolism Disorders Based on a New Model of Chronic Progressive Heart Failure
Molecular BioSystems.
Dec, 2013 |
Pubmed ID: 24108264 Background: Despite major advances in the treatment of heart failure (HF), it remains the major cause of mortality and morbidity worldwide. Experimental models of HF typically utilize acute myocardial infarction. However, the majority of clinical HFs occur gradually by a chronic progressive mechanism. Thus, more relevant models are required to aid identification, quantification, and characterization of HF, and its underlying mechanisms. Methods and findings: We developed a model of progressive chronic heart failure (CHF) in the mini-swine by placement of an ameroid constrictor on the left anterior descending coronary artery (LAD). This model demonstrated a steady decline in the cardiac function from 8 to 12 weeks, with a 50% reduction in the ejection fraction. Further, the proteomic, metabolomic and bioinformatic analyses of ischemic tissue and plasma revealed a significant alteration of the mitochondrial respiratory chain mediated by nicotinamide adenine dinucleotide (NADH), which resulted in down-regulation of malate dehydrogenase (MDH) and insufficient energy supply to support cardiac contractility and relaxation. Furthermore, significant changes in apolipoprotein A-I, low density lipoprotein (LDL), and very LDL (VLDL) in plasma indicated that lipid metabolism disorders occurred in mini-swines with myocardial ischemia via glycerolipid metabolism. Conclusions: We describe a stable and easily reproducible CHF model using an ameroid constrictor placed on the LAD. We found that the NADH-mediated tricarboxylic acid cycle and energy metabolism disorders are key pathophysiological mechanisms underlying CHF. These data will provide potential biomarkers for monitoring the therapeutic intervention of CHF.
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A Protective Role of Sulforaphane on Alveolar Epithelial Cells Exposed to Cigarette Smoke Extract
Experimental Lung Research.
Nov, 2013 |
Pubmed ID: 24117145 ABSTRACT Background: Sulforaphane (SFN) is an excellent antioxidant agent, few of the studies focus on the possible protective role of SFN from cigarette smoke-induced injury on alveolar epithelial cells. Objectives: the aim of the study is to observe the possible protective role of SFN, as well as the function of insulin-like growth factor binding protein-3 (IGFBP-3) in the process. Methods: MTT assay was used to evaluate cell viability after cigarette smoke extract (CSE) and/or SFN exposure, cell cycle was analyzed using flow cytometry, intracellular reactive oxygen species (ROS) level was detected by staining with fluorescent indicator 2', 7'-dichlorofluorescin diacetate (DCFH-DA), finally both real-time quantitative RT-PCR and western blot were employed to observe mRNA and protein levels of IGFBP-3. Results: SFN could restore the viability of A549 cells, attenuate G1 block of the cell cycle, and significantly reduce the proportion of sub-G1 cells; at the same time, CSE-induced accumulation of intracellular ROS was decreased by SFN. Interestingly, high expression of IGFBP-3 was found at both transcriptional and translational levels, however by pre-incubation with SFN, the expression of IGFBP-3 was not stimulated by CSE exposure. Conclusions: SFN can antagonize CSE-induced growth arrest of alveolar epithelial cells and IGFBP-3 probably plays an important role in the process.
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Habitat Association and Conservation Implications of Endangered Francois' Langur (Trachypithecus Francoisi)
PloS One.
2013 |
Pubmed ID: 24130730 Francois' langur (Trachypithecus francoisi) is an endangered primate and endemic to the limestone forests of the tropical and subtropical zone of northern Vietnam and South-west China with a population of about 2,000 individuals. Conservation efforts are hampered by limited knowledge of habitat preference in its main distribution area. We surveyed the distribution of Francois' langur and modeled the relationship between the probability of use and habitat features in Mayanghe National Nature Reserve, Guizhou, China. The main objectives of this study were to provide quantitative information on habitat preference, estimating the availability of suitable habitat, and providing management guidelines for the effective conservation of this species. By comparing 92 used locations with habitat available in the reserve, we found that Francois' langur was mainly distributed along valleys and proportionally, used bamboo forests and mixed conifer-broadleaf forests more than their availability, whereas they tended to avoid shrubby areas and coniferous forests. The langur tended to occur at sites with lower elevation, steeper slope, higher tree canopy density, and a close distance to roads and water. The habitat occupancy probability was best modeled by vegetation type, vegetation coverage, elevation, slope degree, distances to nearest water, paved road, and farmland edge. The suitable habitat in this reserve concentrated in valleys and accounted for about 25% of the total reserve area. Our results showed that Francois' langur was not only restricted at the landscapes level at the regions with karst topography, limestone cliffs, and caves, but it also showed habitat preference at the local scale. Therefore, the protection and restoration of the langur preferred habitats such as mixed conifer-broadleaf forests are important and urgent for the conservation of this declining species.
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Membranes with Highly Ordered Straight Nanopores by Selective Swelling of Fast Perpendicularly Aligned Block Copolymers
ACS Nano.
Oct, 2013 |
Pubmed ID: 24131365 Membranes with uniform, straight nanopores have important applications in diverse fields, but their application is limited by the lack of efficient producing methods with high controllability. In this work, we reported on an extremely simple and efficient strategy to produce such well-defined membranes. We demonstrated that neutral solvents were capable of annealing amphiphilic block copolymer (BCP) films of polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) with thicknesses up to 600 nm to the perpendicular orientation within 1 min. Annealing in neutral solvents was also effective to the perpendicular alignment of block copolymers with very high molecular weights, e.g., 362 000 Da. Remarkably, simply by immersing the annealed BCP films in hot ethanol followed by drying in air, the originally dense BCP films were nondestructively converted into porous membranes containing highly ordered, straight nanopores traversing the entire thickness of the membrane (up to 1.1 μm). Grazing incident small-angle X-ray spectroscopy confirmed the hexagonal ordering of the nanopores over large areas. We found that the overflow of P2VP chains from their reservoir P2VP cylinders and the deformation of the PS matrix in the swelling process contributed to the transformation of the solid P2VP cylinders to empty straight pores. The pore diameters can be tuned by either changing the swelling temperatures or depositing thin layers of metal oxides on the preformed membranes via atomic layer deposition with a subnanometer accuracy. To demonstrate the application of the obtained porous membranes, we used them as templates and produced centimeter-scale arrays of aligned nanotubes of metal oxides with finely tunable wall thicknesses.
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A Novel and Quick Method to Avoid H2O2 Interference on COD Measurement in Fenton System by Na2SO3 Reduction and O2 Oxidation
Water Science and Technology : a Journal of the International Association on Water Pollution Research.
2013 |
Pubmed ID: 24135101 Hydrogen peroxide interference on chemical oxygen demand (COD) measurement has been a big problem in the application of the Fenton process. However, there is no simple and effective method available to address this problem, although several methods have been reported in the literature. In this study, a new method has been developed based on Na2SO3 reduction and O2 oxidation, which has easy operation and short time requirement. Na2SO3 reduction was used to remove H2O2 in water samples, which was independent of pH in the investigated range of 2.50-11.95. Residual Na2SO3 was removed by subsequent O2 oxidation, and effects of initial solution pH, ferric ion dosage, and stirring speed were explored. Solution pH below 3.0 and stirring speed of 700 rev min(-1) could ensure a sufficiently high oxidation rate for Na2SO3 with ferric ion higher than 0.469 mM. This new method was proven to be effective in the matrix of Fenton treating real landfill leachate. Meanwhile, the procedure for this method in other applications was proposed in detail. To the best of our knowledge, this newly developed method is the most simple and effective way to avoid H2O2 interference on COD analysis.
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MicroRNA-224 is Involved in the Regulation of Mouse Cumulus Expansion by Targeting Ptx3
Molecular and Cellular Endocrinology.
Oct, 2013 |
Pubmed ID: 24145127 MicroRNAs (miRNAs) are indicated to regulate ovarian development in a cell- or stage-specific manner. Our previous study showed that miR-224 is involved in TGF-β1-mediated follicular granulosa cell (GC) growth and estradiol (E2) production during the transition from the preantral to early antral stage by targeting Smad4. In this study, miR-224 was found to target pentraxin 3 (Ptx3), a gene critical for cumulus expansion during ovulation. In addition, PTX3 was up-regulated in mouse mural GCs and cumulus-oocyte complexes (COCs) by TGF-β1 treatment, which was partially mediated by miR-224. The effect of miR-224 during ovulation was further examined in vitro and in vivo by construction of an adenovirus-mediated expression vector for miR-224 (Ad-miR-224). In vitro studies demonstrated that miR-224 could perturb cumulus expansion in EGF-stimulated COCs by decreasing PTX3 secretion. In vivo studies also showed that injection of Ad-miR-224 into ovarian bursa decreased PTX3 expression and disrupted ovulation, which led to a decreased number of implantation sites and offspring being born. These results indicate that miR-224 may affect ovulation and subsequent embryo development by targeting Ptx3, suggesting potential roles for miRNAs in offering new treatments for ovulation disorder-associated infertility, or, conversely, designing new contraceptives.
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Small Mammal Community Succession on the Beach of Dongting Lake, China, After the Three Gorges Project
Integrative Zoology.
Oct, 2013 |
Pubmed ID: 24148252 The Three Gorges Project (TGP) may have affected the population structure and distribution of plant and animal communities. However, few studies have analyzed the effect of this project on small mammal communities. Therefore, this paper compares the small mammal communities inhabiting the beaches of Dongting Lake using field investigations spanning a 20-year period, both before and after TGP implementation. Snap traps were used throughout the census. The results indicated that the TGP caused major changes to the structure of the small mammal community at a lake downstream of the dam. First, species abundance on the beaches increased after the project was started. Apodemus agrarius and Rattus norvegicus, which rarely inhabited the beach before the TGP, became abundant (with marked population growth) once water was impounded by the Three Gorges Reservoir. Second, dominant species concentration indices exhibited a stepwise decline, indicating that the community structure changed from a single dominant species to a more diverse species mix after TGP implementation. Third, the regulation of water discharge release by the TGP might have caused an increase in the species diversity of the animal community on the beaches. A significant difference in diversity indices was obtained before and after the TGP operation. Similarity indices also indicated a gradual increase in species numbers. Hence, a long-term project should be established to monitor the population fluctuations of Microtus fortis, A. agrarius, and R. norvegicus to safeguard against population outbreaks (similar to the Yangtze vole outbreak in 2007), which could cause crop damage to adjacent farmland, in addition to documenting the succession process of the small mammal community inhabiting the beaches of Dongting Lake.
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A Novel Algorithm Based on Visual Saliency Attention for Localization and Segmentation in Rapidly-stained Leukocyte Images
Micron (Oxford, England : 1993).
Oct, 2013 |
Pubmed ID: 24148877 In this paper, we propose a fast hierarchical framework of leukocyte localization and segmentation in rapidly-stained leukocyte images (RSLI) with complex backgrounds and varying illumination. The proposed framework contains two main steps. First, a nucleus saliency model based on average absolute difference is built, which locates each leukocyte precisely while effectively removes dyeing impurities and erythrocyte fragments. Secondly, two different schemes are presented for segmenting the nuclei and cytoplasm respectively. As for nuclei segmentation, to solve the overlap problem between leukocytes, we extract the nucleus lobes first and further group them. The lobes extraction is realized by the histogram-based contrast map and watershed segmentation, taking into account the saliency and similarity of nucleus color. Meanwhile, as for cytoplasm segmentation, to extract the blurry contour of the cytoplasm under instable illumination, we propose a cytoplasm enhancement based on tri-modal histogram specification, which specifically improves the contrast of cytoplasm while maintaining others. Then, the contour of cytoplasm is quickly obtained by extraction based on parameter-controlled adaptive attention window. Furthermore, the contour is corrected by concave points matching in order to solve the overlap between leukocytes and impurities. The experiments show the effectiveness of the proposed nucleus saliency model, which achieves average localization accuracy with F1-measure greater than 95%. In addition, the comparison of single leukocyte segmentation accuracy and running time has demonstrated that the proposed segmentation scheme outperforms the former approaches in RSLI.
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Molecular Characterization of Msp2/p44 of Anaplasma Phagocytophilum Isolated from Infected Patients and Haemaphysalis Longicornis in Laizhou Bay, Shandong Province, China
PloS One.
2013 |
Pubmed ID: 24167608 Molecular characterization of the MSP2/P44 protein of Anaplasma phagocytophilum may determine not only if the bacterium is capable of invading hosts but also whether it generates antigenic variation for the purpose of escaping the host immune response, resulting in various pathologic injuries and serious clinical outcomes. Chinese anaplasmosis patients usually present with serious manifestations, and the fatality rate is as high as 26.5%. In this study, we amplified, cloned and sequenced the msp2/p44 genes of three Chinese A. phagocytophilum isolates from Laizhou Bay, Shandong Province, where human granulocytic anaplasmosis (HGA) patients present severe clinical manifestations, and analyzed their genetic characterization and structural features. We also compared them with the HZ and Webster A. phagocytophilum strains. The sequences for both strains are available in GenBank. Analyses indicated that Chinese A. phagocytophilum isolates were significantly different from the HZ and Webster strains in terms of nucleotide sequences, amino acid sequences and protein secondary and tertiary structures. Moreover, the number of immunologic B-cell epitopes (19) of the MSP2 protein of the Chinese isolates was higher than that of the A. phagocytophilum strains HZ (16) and Webster (9). This genetic diversity of the MSP2/P44 protein of Chinese A. phagocytophilum isolates might be relevant and might have serious clinical outcomes. This observation could provide a clue to further understand the pathogenesis of Chinese A. phagocytophilum.
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The Theta-related Firing Activity of Parvalbumin-positive Neurons in the Medial Septum-diagonal Band of Broca Complex and Their Response to 5-HT1A Receptor Stimulation in a Rat Model of Parkinson's Disease
Hippocampus.
Oct, 2013 |
Pubmed ID: 24174292 The parvalbumin (PV)-positive neurons in the medial septum-diagonal band of Broca complex (MS-DB) play an important role in the generation of hippocampal theta rhythm involved in cognitive functions. These neurons in this region express a high density of 5-HT1A receptors which regulate the neuronal activity and consequently affect the theta rhythm. In this study, we examined changes in the theta-related firing activity of PV-positive neurons in the MS-DB, their response to 5-HT1A receptor stimulation and the corresponding hippocampal theta rhythm, and the density of PV-postitive neurons and their co-localization with 5-HT1A receptors in rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc). The lesion of the SNc decreased the rhythmically bursting activity of PV-positive neurons and the peak frequency of hippocampal theta rhythm. Systemic administration of 5-HT1A receptor agonist 8-OH-DPAT (0.5-128 µg/kg, i.v.) inhibited the firing rate of PV-positive neurons and disrupted rhythmically bursting activity of the neurons and the theta rhythm in sham-operated and the lesioned rats, respectively. The cumulative doses producing inhibition and disruption in the lesioned rats were higher than that of sham-operated rats. Furthermore, local application of 8-OH-DPAT (0.005 μg) in the MS-DB also inhibited the firing rate of PV-positive neurons and disrupted their rhythmically bursting activity in sham-operated rats, while having no effect on PV-positive neurons in the lesioned rats. The lesion of the SNc decreased the density of PV-postive neurons in the MS-DB, and percentage of PV-positive neurons expressing 5-HT1A receptors. These results indicate that the lesion of the SNc leads to suppression of PV-positive neurons in the MS-DB and hippocampal theta rhythm. Furthermore, the lesion decreases the response of these neurons to 5-HT1A receptor stimulation, which attributes to dysfunction and/or down-regulation of 5-HT1A receptor expression on these neurons. These changes may be involved in cognitive impairments of Parkinson's disease. © 2013 Wiley Periodicals, Inc.
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Glycyrrhetinic Acid-modified Chitosan Nanoparticles Enhanced the Effect of 5-fluorouracil in Murine Liver Cancer Model Via Regulatory T-cells
Drug Design, Development and Therapy.
2013 |
Pubmed ID: 24187487 Modified chitosan nanoparticles are a promising platform for drug, such as 5-fluorouracil (5-FU), gene, and vaccine delivery. Here, we used chitosan and hepatoma cell-specific binding molecule glycyrrhetinic acid (GA) to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by infrared spectroscopy and hydrogen nuclear magnetic resonance. By combining GA-CTS and 5-FU, we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 193.7 nm, drug loading of 1.56%, and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained-release system comprising three distinct phases of quick, steady, and slow release. In vitro data indicated that it had a dose- and time-dependent anticancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited cancer cell proliferation, resulting in increased survival time. The antitumor mechanisms for GA-CTS/5-FU nanoparticle were possibly associated with an increased expression of regulatory T-cells, decreased expression of cytotoxic T-cell and natural killer cells, and reduced levels of interleukin-2 and interferon gamma.
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Effective Key Parameter Determination for an Automatic Approach to Land Cover Classification Based on Multispectral Remote Sensing Imagery
PloS One.
2013 |
Pubmed ID: 24204582 The classification of land cover based on satellite data is important for many areas of scientific research. Unfortunately, some traditional land cover classification methods (e.g. known as supervised classification) are very labor-intensive and subjective because of the required human involvement. Jiang et al. proposed a simple but robust method for land cover classification using a prior classification map and a current multispectral remote sensing image. This new method has proven to be a suitable classification method; however, its drawback is that it is a semi-automatic method because the key parameters cannot be selected automatically. In this study, we propose an approach in which the two key parameters are chosen automatically. The proposed method consists primarily of the following three interdependent parts: the selection procedure for the pure-pixel training-sample dataset, the method to determine the key parameters, and the optimal combination model. In this study, the proposed approach employs both overall accuracy and their Kappa Coefficients (KC), and Time-Consumings (TC, unit: second) in order to select the two key parameters automatically instead of using a test-decision, which avoids subjective bias. A case study of Weichang District of Hebei Province, China, using Landsat-5/TM data of 2010 with 30 m spatial resolution and prior classification map of 2005 recognised as relatively precise data, was conducted to test the performance of this method. The experimental results show that the methodology determining the key parameters uses the portfolio optimisation model and increases the degree of automation of Jiang et al.'s classification method, which may have a wide scope of scientific application.
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Knockdown of TrkA in Cumulus Oocyte Complexes (COCs) Inhibits EGF-induced Cumulus Expansion by Down-regulation of IL-6
Molecular and Cellular Endocrinology.
Nov, 2013 |
Pubmed ID: 24215827 Tyrosine kinase receptor A (TrkA), the high-affinity receptor of nerve growth factor (NGF), is known to play key roles in ovarian follicular development, such as assembly of early follicles and follicular ovulation. However, little is known about the roles of TrkA in cumulus oocyte complex (COC) expansion. In this study, we found that TrkA was abundant in large antral follicles and knockdown of TrkA in COCs attenuated epidermal growth factor (EGF)-induced COC expansion and further decreased the ovulation rate. The effect of TrkA on COC expansion was not mediated through downstream EGF effectors, phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) or drosophila mothers against decapentaplegic protein (SMAD), or through up-regulation of COC expansion-related transcripts such as prostaglandin-endoperoxide synthase 2 (Ptgs2), hyaluronan synthase 2 (Has2), TNF-induced protein 6 (Tnfaip6) or pentraxin 3 (Ptx3). However, pharmacological blockade of TrkA transducing activity (K252α) in COCs decreased the mRNA expression and protein secretion of interleukin-6 (IL-6), identified from mRNA microarray of K252α-treated COCs. Meanwhile, knockdown of IL-6 attenuated EGF-induced COC expansion. In addition, IL-6 rescued the inhibitory effect of K252α on EGF-induced cumulus expansion. Therefore, IL-6 may act as a new potential cumulus expansion-related transcript, which may be involved in the integration of TrkA and EGF signaling in affecting COC expansion. Here, we provide mechanistic insights into the roles of TrkA in EGF-induced cumulus expansion. Understanding potential cross-points between TrkA and EGF affecting cumulus expansion will help in the discovery of new therapeutic targets in ovulation-related diseases.
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Downregulated RASD1 and Upregulated MiR-375 Are Involved in Protective Effects of Calycosin on Cerebral Ischemia/reperfusion Rats
Journal of the Neurological Sciences.
Apr, 2014 |
Pubmed ID: 24548484 Isoflavone calycosin is a typical phytoestrogen extracted from Chinese medical herb Radix Astragali. It has been reported that estrogens could provide neuroprotective effects, and dietary intake of phytoestrogens could reduce stroke injury in cerebral ischemia/reperfusion (I/R) animal models. In the present study, we investigate the molecular mechanisms underlying the neuroprotective effects of calycosin on middle cerebral artery occlusion (MCAO) rats. Focal cerebral ischemia was induced in male rats by MCAO, neurological deficits and brain edema was evaluated after 24h of reperfusion. The results shown calycosin significantly reduced the infarcted volume and the brain water content, and improved the neurological deficit. To provide insight into the functions of estrogen receptor (ER)-mediated signaling pathway in neuroprotection by calycosin, the expression of miR-375, ER-α, RASD1 (Dexamethasone-induced Ras-related protein 1) and Bcl-2 was determined by RT-PCR or western blot assay. Calycosin exhibited a downregulation of RASD1, and an upregulation of ER-α, miR-375 and Bcl-2. Our finding illustrated that calycosin had been shown neuroprotective effects in cerebral ischemia/reperfusion rats, and the molecular mechanisms may correlate with the positive feedback between ER-α and miR-375, along with the regulation of downstream targets.
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Toxoplasma Gondii Inhibits Apoptosis Via a Novel STAT3-miR-17-92-Bim Pathway in Macrophages
Cellular Signalling.
Jun, 2014 |
Pubmed ID: 24583285 In order to accomplish their life cycles, intracellular pathogens, including the apicomplexan Toxoplasma gondii, subvert the innate apoptotic response of infected host cells. However, the precise mechanisms of parasite interference with the apoptotic pathway remain unclear. MicroRNAs (miRNAs) regulate gene expression at the posttranscriptional level. Using T. gondii strain TgCtwh3, which was isolated from felids and possesses the predominant genotype China 1 (ToxoDB(#)9) in China, we analyzed the miRNA expression profile of human macrophages challenged with TgCtwh3. The results showed that miR-17-92 miRNA expression was significantly increased and Bim was decreased in TgCtwh3-infected cells. Database analysis of miR-17-92 miRNAs revealed the potential binding sites in the 3'UTR of Bim, one of the crucial effectors of pro-apoptosis. Furthermore, we demonstrated that the promoter of the miR-17-92 gene cluster which encodes miRNAs was transactivated through the promoter binding of the STAT3 following TgCtwh3 infection. Taken together, we describe a novel STAT3-miR-17-92-Bim pathway, thus providing a mechanistic explanation for inhibition of apoptosis of host cells following Toxoplasma infection.
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Genome-wide Microarray Analysis Identifies a Potential Role for Striatal Retrograde Endocannabinoid Signaling in the Pathogenesis of Experimental L-DOPA-induced Dyskinesia
Synapse (New York, N.Y.).
Aug, 2014 |
Pubmed ID: 24599755 l-3,4-Dihydroxyphenylalanine (L-DOPA) is the most widely used drug for the treatment of Parkinson's disease. Unfortunately, chronic administration of this dopamine precursor causes L-DOPA-induced dyskinesia (LID), which is a debilitating complication whose pathogenesis remains unclear. In this study, we compared gene expression profiles of sensorimotor striatum tissue derived from LID and non-LID 6-hydroxydopamine-lesioned rats treated with L-DOPA. Total RNA was amplified, transcribed and hybridized to Agilent Whole Rat Genome Oligo Microarray chips. Quantitative real-time reverse transcription PCR was conducted to validate the microarray data. We detected 382 upregulated genes and 115 downregulated genes in LID rats when compared with that of non-LID subjects with Significance Analysis for Microarrays software. The differentially expressed genes were mainly associated with postsynaptic cell membranes, synapses, and neurotransmitter receptors. Gene Set Analysis (GSA) software was used to identify differentially expressed gene ontology (GO) categories and pathways. The GSA found that "long-term depression" and "retrograde endocannabinoid signaling" pathways were downregulated, whereas a set of lipid metabolism-related GO categories and pathways were upregulated in LID rats compared with non-LID controls. Our study provides further experimental evidence to support the direct correlation between abnormal striatal synaptic plasticity and the induction of LID, and it suggests that the dysfunction of the retrograde endocannabinoid signaling system, a lipid-based neuromodulatory system, and the relevant alteration of the related lipid metabolism processes might play an important role in the pathogenesis of LID.
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Development of Serum Parameters Panels for the Early Detection of Pancreatic Cancer
International Journal of Cancer. Journal International Du Cancer.
Jun, 2014 |
Pubmed ID: 24615168 Early detection of pancreatic cancer is promising for improving clinical outcome; however, no effective biomarker has yet been identified. Here, we detected 61 clinical serum parameters in 200 healthy controls (Ctrls), 163 pancreatic ductal adenocarcinoma (PDAC) patients and 109 benign pancreatitis patients (Benign) in the training group. A metropolis algorithm with Monte Carlo simulation was used for identifying parameter panels. Sera from 183 Ctrl, 129 PDAC and 95 Benign individuals were used for cross-validation. Samples from 77 breast, 72 cervical, 101 colorectal, 138 gastric, 108 prostate and 132 lung cancer patients were collected for evaluating cancer selectivity. A panel consisting of carbohydrate antigen (CA)19-9, albumin (ALB), C-reactive protein (CRP) and interleukin (IL)-8 had the highest diagnostic value for discriminating between PDAC and Ctrl. The sensitivity (SN) was 99.39% for all-stage, 96.10% for early-stage and 98.80% for advanced-stage PDAC at 90% specificity (SP). In the validation group, the sensitivities were 93.80, 93.10 and 94.40%, respectively, at 90% SP. This panel also identified 80.52% of the breast cancer, 66.67% cervical cancer, 86.14% colorectal cancer, 89.86% gastric cancer, 71.30% prostate cancer and 93.85% lung cancer samples as non-PDAC. The panel consisting of CA19-9, carbon dioxide, CRP and IL-6 panel had the highest diagnostic value for discriminating between PDAC and Benign. The SN was 74.23% for all-stage, 75.30% for early-stage and 74.40% for advanced-stage PDAC at 90% SP. In the validation group, the sensitivities were 72.10, 76.10 and 67.20%, respectively, at 90% SP. Our parameter panels may aid in the early detection of PDAC to improve clinical outcome.
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Calycosin Suppresses Breast Cancer Cell Growth Via ERβ-dependent Regulation of IGF-1R, P38 MAPK and PI3K/Akt Pathways
PloS One.
2014 |
Pubmed ID: 24618835 We previously reported that calycosin, a natural phytoestrogen structurally similar to estrogen, successfully triggered apoptosis of estrogen receptor (ER)-positive breast cancer cell line, MCF-7. To better understand the antitumor activities of calycosin against breast cancer, besides MCF-7 cells, another ER-positive cell line T-47D was analyzed here, with ER-negative cell lines (MDA-231, MDA-435) as control. Notably, calycosin led to inhibited cell proliferation and apoptosis only in ER-positive cells, particularly in MCF-7 cells, whereas no such effect was observed in ER-negative cells. Then we investigated whether regulation of ERβ, a subtype of ER, contributed to calycosin-induced apoptosis in breast cancer cells. The results showed that incubation of calycosin resulted in enhanced expression ERβ in MCF-7 and T-47D cells, rather than MDA-231 and MDA-435 cells. Moreover, with the upregulation of ERβ, successive changes in downstream signaling pathways were found, including inactivation of insulin-like growth factor 1 receptor (IGF-1R), then stimulation of p38 MAPK and suppression of the serine/threonine kinase (Akt), and finally poly(ADP-ribose) polymerase 1 (PARP-1) cleavage. However, the other two members of the mitogen-activated protein kinase (MAPK) family, extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK), were not consequently regulated by downregulated IGF-1R, indicating ERK 1/2 and JNK pathways were not necessary to allow proliferation inhibition by calycosin. Taken together, our results indicate that calycosin tends to inhibit growth and induce apoptosis in ER-positive breast cancer cells, which is mediated by ERβ-induced inhibition of IGF-1R, along with the selective regulation of MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt pathways.
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Total Body Irradiation Causes Long-term Mouse BM Injury Via Induction of HSC Premature Senescence in an Ink4a- and Arf-independent Manner
Blood.
May, 2014 |
Pubmed ID: 24622326 Exposure to total body irradiation (TBI) induces not only acute hematopoietic radiation syndrome but also long-term or residual bone marrow (BM) injury. This residual BM injury is mainly attributed to permanent damage to hematopoietic stem cells (HSCs), including impaired self-renewal, decreased long-term repopulating capacity, and myeloid skewing. These HSC defects were associated with significant increases in production of reactive oxygen species (ROS), expression of p16(Ink4a) (p16) and Arf mRNA, and senescence-associated β-galacotosidase (SA-β-gal) activity, but not with telomere shortening or increased apoptosis, suggesting that TBI induces residual BM injury via induction of HSC premature senescence. This suggestion is supported by the finding that SA-β-gal(+) HSC-enriched LSK cells showed more pronounced defects in clonogenic activity in vitro and long-term engraftment after transplantation than SA-β-gal(-) LSK cells isolated from irradiated mice. However, genetic deletion of p16 and/or Arf had no effect on TBI-induced residual BM suppression and HSC senescence, because HSCs from irradiated p16 and/or Arf knockout (KO) mice exhibited changes similar to those seen in HSCs from wild-type mice after exposure to TBI. These findings provide important new insights into the mechanism by which TBI causes long-term BM suppression (eg, via induction of premature senescence of HSCs in a p16-Arf-independent manner).
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The Relationship Between Frequency Dependence of Action Potential Duration and the Expression of TRPC3 in Rabbit Ventricular Myocardium
Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology.
2014 |
Pubmed ID: 24642929 Background/Aims: Cardiac action potential duration (APD) is regulated by heart rate, leading to the trans-membrane movement of inorganic ions. Whether the alteration of heart rate can affect the expression of transient receptor potential canonical channels (TRPCs), further studies should be made. We investigated the changes of APD at different stimulus frequencies and their influences on the expression of TRPCs in rabbit ventricular myocardium. Methods: Monophasic action potential (MAP) was recorded by contact electrode technique in different programmed stimulus frequencies on rabbit ventricular epicardium in vivo, and the expression of TRPCs was detected using RT-PCR and Western blot. Results: At the frequency range of 4.5-7.5 Hz, APD gradually shortened with the increase of stimulus frequency, showing the property of significant frequency dependence in rabbit ventricular myocardium in vivo. Compared with 4.5 Hz group, TRPC3 mRNA and protein expression increased in 6 Hz and 7.5 Hz groups by way of frequency dependence. Both amiodarone (AM) and neferine (Nef) could prolongate APD and showed characters of frequency independence at the designed frequency. In contrast with 4.5 Hz control group, it was Nef treatment group rather than AM treatment group that could obviously increase the expression of TRPC3 mRNA and protein. Conclusions: At the frequency range of 4.5-7.5 Hz, frequency-dependent shortening of APD was associated with the expression of TRPC3. AM and Nef exhibited frequency-independent lengthening of the APD. Nef may prolong APD via the increasement of TRPC3. © 2014 S. Karger AG, Basel.
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Neurocognitive Improvement After Carotid Artery Stenting in Patients with Chronic Internal Carotid Artery Occlusion: a Prospective, Controlled, Single-center Study
Vascular and Endovascular Surgery.
May, 2014 |
Pubmed ID: 24643000 Symptomatic internal carotid artery (ICA) occlusion with hemodynamic impairment remains a dismal disease when untreated. In this prospective, single-center, controlled study, we investigated the feasibility, safety, and long-term outcome of stenting by endovascular recanalization for patients with chronic ICA occlusion. Forty patients with symptomatic chronically occluded ICA were assigned to receive endovascular recanalization (group A, n = 18) or conservative management (group B, n = 22). The primary end point was 100% complete recanalization of the primary occlusion at 60 minutes, and secondary end points were improvement in neurologic function and cognitive function. Patients in the 2 groups were comparable in demographic and baseline characteristics. Successful recanalization was achieved in 88.9% (16 of 18) of patients with the restoration of Thrombolysis in Myocardial Ischemia/Thrombolysis in Cerebral Ischemia 2 or 3 flow. There was no procedural or new cerebral ischemic event. Improvement in brain perfusion was observed in 12 (12 of 18, 75%) patients on single-photon emission computed tomography. Improvement in neurologic function defined as a reduction of ≥4 points on the National Institutes of Health Stroke Scale (NIHSS) at 6 months was observed in group A (baseline, 6.83 ± 3.01 vs 6 months, 2.61 ± 1.20; P < .01) and group B (baseline, 6.05 ± 2.75 vs 6 months, 4.77 ± 1.69; P < .05). A significant difference in NIHSS scores was noted between group A and B at 1, 3, and 6 months (P < .05 or .001). Improvement in cognitive function defined as an increase of ≥8 on the Montreal Cognitive Assessment (MoCA) was observed in group A at 3 and 6 months (baseline, 14.67 ± 3.56 vs 3 months, 24.17 ± 3.55 and 6 months, 24.72 ± 2.85; P < .01). Significant improvement in MoCA was also observed in group B (P < .01). Furthermore, a significant difference in MoCA scores was noted between group A and B at 1, 3, and 6 months (P < .05 or .001). Endovascular recanalization is feasible and safe for patients with symptomatic chronic carotid artery occlusion. Successful carotid artery stenting can improve neurological function and global cognitive function than nonrevascularization.
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Identification of Novel Knockout and Up-regulated Targets for Improving Isoprenoid Production in E. Coli
Biotechnology Letters.
May, 2014 |
Pubmed ID: 24658737 Discovery of novel potential genetic targets to increase the supply of isoprenoid precursors, isopentyl/dimethylallyl diphosphate, is of importance for microbial production of isoprenoids. Here, to improve isoprenoid precursor supply, a flux distribution comparison analysis, based on the genome-scale model, was utilized to simultaneously predict the knockout, down- and up-regulated targets in Escherichia coli. 51 targets were in silico discovered. All knockout and up-regulated targets were experimentally tested to enhance lycopene production. Five knockout targets (deoB, yhfw, yahI, pta and eutD) and four up-regulated targets (ompN, ompE, ndk and cmk) led to 10-45% increases of lycopene yield, respectively, which had not been uncovered in previous studies. When engineering of the five most significant targets gdhA, eutD, tpiA, ompE and ompN, were combined the lycopene titer improved by 174% in shake-flask and 81% in bioreactor fermentations with a maximum yield of 454 mg l(-1).
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The Quantitative and Functional Changes of NK Cells in Mice Infected with Angiostrongylus Cantonensis
Parasitology Research.
Jun, 2014 |
Pubmed ID: 24667973 Angiostrongylus cantonensis is a neurotropic parasite which can cause injury to central nervous system and eosinophilic meningitis to human. Natural killer (NK) cells are specialized innate lymphocytes important in early defense against pathogens as in a variety of intracellular bacterial, viral, and protozoan infections. However, the number and function of NK cells in extracellular parasitic infection of A. cantonensis are unclear. In this study, on A. cantonensis infected mice which may mimic the human's infection, we found that the percentage of splenic NK cells and the absolute number of peripheral blood NK cells were decreased at 21-day post infection compared with that of controls. When administrating with albendazole treatment at early stage of the infection, the changes of NK cells could be avoided. Further analysis confirmed that the reduction of NK cells was due to their apoptosis manifested as increased expressions of annexin V and activated caspase-3 after 16-day post infection. Moreover, both activated and inhibitory receptors such as CD16, CD69, NKG2D, and Ly49a on NK cells were down-regulated after 16-day post infection. Interestingly, NK cells isolated from mice of 21-day post infection showed enhanced IFN-γ production when stimulated with IL-12 for 24 h and cytotoxicity to YAC-1 cells, as well as elevated CD107a expression. It is evident that NK cell population and its function were changed in A. cantonensis infected mice, suggesting their involvement in pathogenesis of the infection.
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Even Mildly Elevated TSH is Associated with an Atherogenic Lipid Profile in Postmenopausal Women with Subclinical Hypothyroidism
Endocrine Research.
Mar, 2014 |
Pubmed ID: 24679183 Abstract Postmenopausal women, a population with increased risk of atherosclerosis, also have an appreciable risk of subclinical hypothyroidism (SCH). The current study sought an association between serum thyrotropin (TSH), the biomarker of SCH and atherosclerosis lipid profile changes. A total of 45 postmenopausal women with SCH and 27 healthy women matched by age and body mass index were enrolled in this observational study. Serum lipid profiles and thyroid function were assessed. Compared with healthy controls, the serum levels of TC, TG, LDL-c and oxidized LDL (oxLDL) in SCH were increased by ∼22.8%, 29.6%, 30.5% and 23.2%, respectively. TSH was positively correlated with TC, LDL-c and oxLDL in all of the study subjects after adjusting for age and BMI. In particular, the positive correlation remained significant after adjusting for serum FT3 and FT4. When further stratified by TSH levels, both the subgroup of mildly elevated TSH (4.78-9.99 mU/L) and overtly elevated TSH (>10.00 mU/L) exhibited significantly higher serum levels of TC, TG, LDL-c and oxLDL compared to the normal TSH subgroup. Path analysis revealed that the total effects of TSH on TC (total effectsTC,TSH = 0.4323) included a significant direct effect (direct effectTC,TSH = 0.4932) and an indirect effect via an intermediary variable (FT3, FT4). Furthermore, TC exhibited a direct effect on LDL-c, as did LDL-c on oxLDL. In conclusion, even with a mild elevation of serum TSH, SCH is associated with atherogenic lipid profiles in postmenopausal women independent of thyroid hormones.
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A Reduced Graphene Oxide Supported Cu(3)SnS(4) Composite As an Efficient Visible-light Photocatalyst
Dalton Transactions (Cambridge, England : 2003).
May, 2014 |
Pubmed ID: 24686717 In this study, a visible light responsive Cu3SnS4/reduced graphene oxide (RGO) photocatalyst has been synthesized by a facile one-step solvothermal method. The as-synthesized samples were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, N2 adsorption-desorption, UV-vis diffuse reflectance spectra (DRS), and photoluminescence (PL) emission spectroscopy. The photocatalytic activity of the Cu3SnS4/RGO composite under visible-light irradiation (λ > 420 nm) was evaluated by measuring the degradation of rhodamine B (RhB) and phenol. The results revealed that the Cu3SnS4 nanoplates dispersed uniformly on the RGO surface. The Cu3SnS4/RGO composite exhibited much higher photocatalytic activity than pure Cu3SnS4. The enhancement in photocatalytic activity is likely to be due to the synergistic effect of an improved adsorptivity of pollutants, an enhanced visible light absorption and an effective charge separation. In addition, the Cu3SnS4/RGO photocatalyst was stable during the reaction and could be used repeatedly.
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Symbiotic Adaptation Drives Genome Streamlining of the Cyanobacterial Sponge Symbiont "Candidatus Synechococcus Spongiarum"
MBio.
2014 |
Pubmed ID: 24692632 "Candidatus Synechococcus spongiarum" is a cyanobacterial symbiont widely distributed in sponges, but its functions at the genome level remain unknown. Here, we obtained the draft genome (1.66 Mbp, 90% estimated genome recovery) of "Ca. Synechococcus spongiarum" strain SH4 inhabiting the Red Sea sponge Carteriospongia foliascens. Phylogenomic analysis revealed a high dissimilarity between SH4 and free-living cyanobacterial strains. Essential functions, such as photosynthesis, the citric acid cycle, and DNA replication, were detected in SH4. Eukaryoticlike domains that play important roles in sponge-symbiont interactions were identified exclusively in the symbiont. However, SH4 could not biosynthesize methionine and polyamines and had lost partial genes encoding low-molecular-weight peptides of the photosynthesis complex, antioxidant enzymes, DNA repair enzymes, and proteins involved in resistance to environmental toxins and in biosynthesis of capsular and extracellular polysaccharides. These genetic modifications imply that "Ca. Synechococcus spongiarum" SH4 represents a low-light-adapted cyanobacterial symbiont and has undergone genome streamlining to adapt to the sponge's mild intercellular environment. IMPORTANCE Although the diversity of sponge-associated microbes has been widely studied, genome-level research on sponge symbionts and their symbiotic mechanisms is rare because they are unculturable. "Candidatus Synechococcus spongiarum" is a widely distributed uncultivated cyanobacterial sponge symbiont. The genome of this symbiont will help to characterize its evolutionary relationship and functional dissimilarity to closely related free-living cyanobacterial strains. Knowledge of its adaptive mechanism to the sponge host also depends on the genome-level research. The data presented here provided an alternative strategy to obtain the draft genome of "Ca. Synechococcus spongiarum" strain SH4 and provide insight into its evolutionary and functional features.
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Natural Killer Cell Intrinsic Toll-like Receptor MyD88 Signaling Contributes to IL-12-dependent IFN-γ Production by Mice During Infection with Toxoplasma Gondii
International Journal for Parasitology.
Jun, 2014 |
Pubmed ID: 24727091 Myeloid differentiation factor 88 (MyD88)-dependent IL-12 secretion by dendritic cells is critical for natural killer cell-mediated IFN-γ production and innate resistance to Toxoplasma gondii. Although MyD88(-/-) mice challenged with T. gondii have defective IL-12 responses and succumb to infection, administration of IL-12 to MyD88(-/-) mice fails to prevent acute mortality, suggesting that MyD88 may mediate signals within natural killer cells important for IL-12-dependent IFN-γ production and innate resistance to this parasite. In this study, we found that T. gondii antigens and IL-12 could synergistically trigger IFN-γ secretion by natural killer cells, which was dependent on toll-like receptor-MyD88 signaling. Further analysis showed that p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, c-Jun N-terminal kinase and NF-κB multiple pathways downstream of MyD88 contributed to IFN-γ production by natural killer cells. Moreover, the well-established toll-like receptor agonists, T. gondii profilin (Tgprofilin) and T. gondii heat shock protein 70 (TgHSP70) could evoke a similar IFN-γ secretory response in natural killer cells to that evoked by T. gondii antigens. In vivo adoptive transfer experiments showed that, upon challenge with T. gondii, NOD/SCID-β2 microglobulin null (NOD/SCID-β2m(-/-)) mice injected i.v. with MyD88(-/-) natural killer cells had reduced serum IFN-γ levels and increased splenic tachyzoite burdens compared with those injected i.v. with wild-type natural killer cells. Taken together, these findings demonstrate a critical role for natural killer cell intrinsic toll-like receptor-MyD88 signaling in IL-12-dependent early IFN-γ production and innate resistance to T. gondii.
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Effects of Supplemental Copper on the Serum Lipid Profile, Meat Quality, and Carcass Composition of Goat Kids
Biological Trace Element Research.
Jun, 2014 |
Pubmed ID: 24756646 To evaluate the effects of copper (Cu) supplementation on the serum lipid profile, meat quality, and carcass composition of goat kids, thirty-five 3-4-month-old Jian Yang big-eared goat kids (BW 20.3±0.6 kg) were randomly assigned to one of seven dietary Cu treatments (n=5/treatment). The dietary Cu concentrations were: (1) control (no supplemental Cu), (2) 20 mg, (3) 40 mg, (4) 80 mg, (5) 160 mg, (6) 320 mg, and (7) 640 mg of supplemental Cu/kg dry matter (DM). Copper was supplemented as CuSO4.5H2O (25.2 % Cu). The goats were fed a high-concentrate basal diet with the different concentrations of supplemental Cu/kg DM for 96 days. The serum lipid profile was determined on day 51 and day 96. Meat quality and carcass composition of longissimus dorsi muscle were measured after the goats were slaughtered at 96 days. Serum total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) were not affected by treatment (P>0.18). No differences were observed in drip loss, cooking loss, a* (redness/greenness) and b* (yellowness/blueness) values (P>0.17); however, the 24-h pH value (linear; P=0.0009) and L* (brightness) value (linear; P=0.0128) decreased, and shear force increased (linear; P=0.0005) as Cu supplementation increased. The intramuscular fat (%) increased (linear; P=0.001) as supplemental Cu increased. No differences (P>0.21) in the moisture, crude protein, and ash (%) were observed. Results of this study indicate that supplemental Cu does not modify the serum lipid profile; however, it can impact intramuscular fat content and the meat quality of goat kids.
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Pyrosequencing Reveals the Microbial Communities in the Red Sea Sponge Carteriospongia Foliascens and Their Impressive Shifts in Abnormal Tissues
Microbial Ecology.
Oct, 2014 |
Pubmed ID: 24760170 Abnormality and disease in sponges have been widely reported, yet how sponge-associated microbes respond correspondingly remains inconclusive. Here, individuals of the sponge Carteriospongia foliascens under abnormal status were collected from the Rabigh Bay along the Red Sea coast. Microbial communities in both healthy and abnormal sponge tissues and adjacent seawater were compared to check the influences of these abnormalities on sponge-associated microbes. In healthy tissues, we revealed low microbial diversity with less than 100 operational taxonomic units (OTUs) per sample. Cyanobacteria, affiliated mainly with the sponge-specific species "Candidatus Synechococcus spongiarum," were the dominant bacteria, followed by Bacteroidetes and Proteobacteria. Intraspecies dynamics of microbial communities in healthy tissues were observed among sponge individuals, and potential anoxygenic phototrophic bacteria were found. In comparison with healthy tissues and the adjacent seawater, abnormal tissues showed dramatic increase in microbial diversity and decrease in the abundance of sponge-specific microbial clusters. The dominated cyanobacterial species Candidatus Synechococcus spongiarum decreased and shifted to unspecific cyanobacterial clades. OTUs that showed high similarity to sequences derived from diseased corals, such as Leptolyngbya sp., were found to be abundant in abnormal tissues. Heterotrophic Planctomycetes were also specifically enriched in abnormal tissues. Overall, we revealed the microbial communities of the cyanobacteria-rich sponge, C. foliascens, and their impressive shifts under abnormality.
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Guidelines Disconcordance in Acute Bipolar Depression: Data from the National Bipolar Mania Pathway Survey (BIPAS) in Mainland China
PloS One.
2014 |
Pubmed ID: 24763748 With the recent attention to the importance of evidence-based medicine in psychiatry, a number of treatment guidelines have been published. This survey investigated prescribing pattern and predictors for guideline disconcordance in the acute treatment of bipolar depression across mainland China. Pharmacological treatments of 1078 patients with bipolar depression were examined. Guidelines disconcordance was determined by comparing the medication(s) patients were prescribed with the recommendation(s) in the guidelines of the Canadian Network for Mood and Anxiety Treatments. Predictors for guidelines discordance were analyzed with logistic regression. Of the 1078 patients, 50.2% patients were treated against treatment guidelines recommendations. The patients who were treated in general hospitals (OR = 1.53, 95% CI 1.18-1.97), with a depressive episode (OR = 1.67, 95% CI 1.27-2.19) and an older age at first onset (OR = 1.62, 95% CI 1.15-2.28) were more likely to receive guideline-disconcordant treatment than their counterparts. In contrast, the patients with current mental comorbidity, an older age at study entry, a longer duration of disease, and more frequent episodes in past year were less likely to receive guideline-disconcordant treatments than their counterparts with an OR of 0.43 (95% CI 0.24-0.77), 0.52 (95CI% 0.36-0.75), 0.48 (95% CI 0.36-0.65), and 0.50 (95% CI 0.38-0.64), respectively. Our finding suggested the disconcordance with treatment guidelines in patients with an acute bipolar depression is common under naturalistic conditions in mainland China, and the predicting factors correlated with guidelines disconcordance include both psychiatrist-specific (clinicians from general hospitals) and patient-specific features (a depressive episode at first onset, no current co-morbidity with mental disorders, a younger age at study entry, an older age at first onset, shorter duration of disease, and non-frequent episodes in past year).
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Catalytic Fast Pyrolysis of Lignocellulosic Biomass
Chemical Society Reviews.
May, 2014 |
Pubmed ID: 24801125 Increasing energy demand, especially in the transportation sector, and soaring CO2 emissions necessitate the exploitation of renewable sources of energy. Despite the large variety of new energy carriers, liquid hydrocarbon still appears to be the most attractive and feasible form of transportation fuel taking into account the energy density, stability and existing infrastructure. Biomass is an abundant, renewable source of energy; however, utilizing it in a cost-effective way is still a substantial challenge. Lignocellulose is composed of three major biopolymers, namely cellulose, hemicellulose and lignin. Fast pyrolysis of biomass is recognized as an efficient and feasible process to selectively convert lignocellulose into a liquid fuel-bio-oil. However bio-oil from fast pyrolysis contains a large amount of oxygen, distributed in hundreds of oxygenates. These oxygenates are the cause of many negative properties, such as low heating value, high corrosiveness, high viscosity, and instability; they also greatly limit the application of bio-oil particularly as transportation fuel. Hydrocarbons derived from biomass are most attractive because of their high energy density and compatibility with the existing infrastructure. Thus, converting lignocellulose into transportation fuels via catalytic fast pyrolysis has attracted much attention. Many studies related to catalytic fast pyrolysis of biomass have been published. The main challenge of this process is the development of active and stable catalysts that can deal with a large variety of decomposition intermediates from lignocellulose. This review starts with the current understanding of the chemistry in fast pyrolysis of lignocellulose and focuses on the development of catalysts in catalytic fast pyrolysis. Recent progress in the experimental studies on catalytic fast pyrolysis of biomass is also summarized with the emphasis on bio-oil yields and quality.
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Combined NIR/MIR Analysis: a Novel Method for the Classification of Complex Substances Such As Illicium Verum Hook. F. and Its Adulterants
Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy.
Sep, 2014 |
Pubmed ID: 24813283 A novel combined near- and mid-infrared (NIR and MIR) spectroscopic method has been researched and developed for the analysis of complex substances such as the Traditional Chinese Medicine (TCM), Illicium verum Hook. F. (IVHF), and its noxious adulterant, Iuicium lanceolatum A.C. Smith (ILACS). Three types of spectral matrix were submitted for classification with the use of the linear discriminant analysis (LDA) method. The data were pretreated with either the successive projections algorithm (SPA) or the discrete wavelet transform (DWT) method. The SPA method performed somewhat better, principally because it required less spectral features for its pretreatment model. Thus, NIR or MIR matrix as well as the combined NIR/MIR one, were pretreated by the SPA method, and then analysed by LDA. This approach enabled the prediction and classification of the IVHF, ILACS and mixed samples. The MIR spectral data produced somewhat better classification rates than the NIR data. However, the best results were obtained from the combined NIR/MIR data matrix with 95-100% correct classifications for calibration, validation and prediction. Principal component analysis (PCA) of the three types of spectral data supported the results obtained with the LDA classification method.
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Diffusion Basis Spectrum Imaging Detects and Distinguishes Coexisting Subclinical Inflammation, Demyelination and Axonal Injury in Experimental Autoimmune Encephalomyelitis Mice
NMR in Biomedicine.
Jul, 2014 |
Pubmed ID: 24816651 Clinicopathological paradox has hampered significantly the effective assessment of the efficacy of therapeutic intervention for multiple sclerosis. Neuroimaging biomarkers of tissue injury could guide more effective treatment by accurately reflecting the underlying subclinical pathologies. Diffusion tensor imaging-derived directional diffusivity and anisotropy indices have been applied to characterize white matter disorders. However, these biomarkers are sometimes confounded by the complex pathologies seen in multiple sclerosis and its animal models. Recently, a novel technique of diffusion basis spectrum imaging has been developed to quantitatively assess axonal injury, demyelination and inflammation in a mouse model of inflammatory demyelination. Lenaldekar, which inhibits T-cell expansion in a non-cytolytic manner, has been shown to suppress relapses and preserve white matter integrity in mice with experimental autoimmune encephalomyelitis. In this study, relapsing-remitting experimental autoimmune encephalomyelitis was induced through active immunization of SJL/J mice with a myelin proteolipid protein peptide. The therapeutic efficacy of Lenaldekar treatment was evaluated via daily clinical score, cross-sectional ex vivo diffusion basis spectrum imaging examination and histological analysis. Lenaldekar greatly reduced relapse severity and protected white matter integrity in these experimental autoimmune encephalomyelitis mice. Diffusion basis spectrum imaging-derived axial diffusivity, radial diffusivity and restricted diffusion tensor fraction accurately reflected axonal injury, myelin integrity and inflammation-associated cellularity change, respectively. These results support the potential use of diffusion basis spectrum imaging as an effective outcome measure for preclinical drug evaluation.
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Time-Course of the Effects of QSYQ in Promoting Heart Function in Ameroid Constrictor-Induced Myocardial Ischemia Pigs
Evidence-based Complementary and Alternative Medicine : ECAM.
2014 |
Pubmed ID: 24817898 We aim to investigate the therapeutic effects of QSYQ on a pig myocardial ischemia (MI) model and to determine its mechanism of action. The MI model was induced by Ameroid constriction of the left anterior descending coronary (LAD) in Ba-Ma miniature pigs. Four groups were created: model group, digoxin group, QSYQ group, and sham-operated group. Heart function, Ang II, CGMP, TXB2, BNP, and cTnT were evaluated before (3 weeks after operation: 0 weeks) and at 2, 4, and 8 weeks after drug administration. After 8 weeks of administration, the pigs were sacrificed for cardiac injury measurements. Pigs with MI showed obvious histological changes, including BNP, cTnT, Ang II, CGRP, TXB2, and ET, deregulated heart function, and increased levels of apoptotic cells in myocardial tissue. Treatment with QSYQ improved cardiac remodeling by counteracting those events. The administration of QSYQ was accompanied by a restoration of heart function and of the levels of Ang II, CGRP, TXB2, ET BNP, and cTnT. In addition, QSYQ attenuated administration, reduced the apoptosis, and decreased the level of TNF- α and active caspase-3. In conclusion, administration of QSYQ could attenuate Ameroid constrictor induced myocardial ischemia, and TNF- α and active caspase-3 seemed to be the critical potential target of QSYQ.
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SchA-p85-FAK Complex Dictates Isoform-specific Activation of Akt2 and Subsequent PCBP1-mediated Post-transcriptional Regulation of TGFβ-mediated Epithelial to Mesenchymal Transition in Human Lung Cancer Cell Line A549
Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine.
Aug, 2014 |
Pubmed ID: 24819169 A post-transcriptional pathway by which TGF-β modulates expression of specific proteins, Disabled-2 (Dab2) and Interleukin-like EMT Inducer (ILEI), inherent to epithelial to mesenchymal transition (EMT) in murine epithelial cells through Akt2-mediated phosphorylation of poly r(C) binding protein (PCBP1), has been previously elucidated. The aims of the current study were to determine if the same mechanism is operative in the non-small cell lung cancer (NSCLC) cell line, A549, and to delineate the underlying mechanism. Steady-state transcript and protein expression levels of Dab2 and ILEI were examined in A549 cells treated with TGF-β for up to 48 h. Induction of translational de-repression in this model was quantified by polysomal fractionation followed by qRT-PCR. The underlying mechanism of isoform-specific activation of Akt2 was elucidated through a combination of co-immunoprecipitation studies. TGF-β induced EMT in A549 cells concomitant with translational upregulation of Dab2 and ILEI proteins through isoform-specific activation of Akt2 followed by phosphorylation of PCBP1 at serine-43. Our experiments further elucidated that the adaptor protein SchA is phosphorylated at tyrosine residues following TGF-β treatment, which initiated a signaling cascade resulting in the sequential recruitment of p85 subunit of PI3K and focal adhesion kinase (FAK). The SchA-FAK-p85 complex subsequently selectively recruited and activated Akt2, not Akt1. Inhibition of the p85 subunit through phosphorylated 1257 peptide completely attenuated EMT in these cells. We have defined the underlying mechanism responsible for isoform-specific recruitment and activation of Akt2, not Akt1, during TGF-β-mediated EMT in A549 cells. Inhibition of the formation of this complex thus represents an important and novel therapeutic target in metastatic lung carcinoma.
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Rational Design of Berberine-based FtsZ Inhibitors with Broad-spectrum Antibacterial Activity
PloS One.
2014 |
Pubmed ID: 24824618 Inhibition of the functional activity of Filamenting temperature-sensitive mutant Z (FtsZ) protein, an essential and highly conserved bacterial cytokinesis protein, is a promising approach for the development of a new class of antibacterial agents. Berberine, a benzylisoquinoline alkaloid widely used in traditional Chinese and native American medicines for its antimicrobial properties, has been recently reported to inhibit FtsZ. Using a combination of in silico structure-based design and in vitro biological assays, 9-phenoxyalkyl berberine derivatives were identified as potent FtsZ inhibitors. Compared to the parent compound berberine, the derivatives showed a significant enhancement of antibacterial activity against clinically relevant bacteria, and an improved potency against the GTPase activity and polymerization of FtsZ. The most potent compound 2 strongly inhibited the proliferation of Gram-positive bacteria, including methicillin-resistant S. aureus and vancomycin-resistant E. faecium, with MIC values between 2 and 4 µg/mL, and was active against the Gram-negative E. coli and K. pneumoniae, with MIC values of 32 and 64 µg/mL respectively. The compound perturbed the formation of cytokinetic Z-ring in E. coli. Also, the compound interfered with in vitro polymerization of S. aureus FtsZ. Taken together, the chemical modification of berberine with 9-phenoxyalkyl substituent groups greatly improved the antibacterial activity via targeting FtsZ.
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Emergence and Prevalence of Non-H2S-producing Salmonella Enterica Serovar Senftenberg Isolates Belonging to Novel Sequence Type 1751 in China
Journal of Clinical Microbiology.
Jul, 2014 |
Pubmed ID: 24829240 Salmonella enterica serovar Senftenberg is a common nontyphoidal Salmonella serotype which causes human Salmonella infections worldwide. In this study, 182 S. Senftenberg isolates, including 17 atypical non-hydrogen sulfide (H2S)-producing isolates, were detected in China from 2005 to 2011. The microbiological and genetic characteristics of the non-H2S-producing and selected H2S-producing isolates were determined by using pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and clustered regularly interspaced short palindromic repeat (CRISPR) analysis. The phs operons were amplified and sequenced. The 17 non-H2S-producing and 36 H2S-producing isolates belonged to 7 sequence types (STs), including 3 new STs, ST1751, ST1757, and ST1758. Fourteen of the 17 non-H2S-producing isolates belonged to ST1751 and had very similar PFGE patterns. All 17 non-H2S-producing isolates had a nonsense mutation at position 1621 of phsA. H2S-producing and non-H2S-producing S. Senftenberg isolates were isolated from the same stool sample from three patients; isolates from the same patients displayed the same antimicrobial susceptibility, ST, and PFGE pattern but could be discriminated based on CRISPR spacers. Non-H2S-producing S. Senftenberg isolates belonging to ST1751 have been prevalent in Shanghai, China. It is possible that these emerging organisms will disseminate further, because they are difficult to detect. Thus, we should strengthen the surveillance for the spread of this atypical S. Senftenberg variant.
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[Effects of Plastic Film Mulching and Rain Harvesting Modes on Chlorophyll Fluorescence Characteristics, Yield and Water Use Efficiency of Dryland Maize]
Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology / Zhongguo Sheng Tai Xue Xue Hui, Zhongguo Ke Xue Yuan Shenyang Ying Yong Sheng Tai Yan Jiu Suo Zhu Ban.
Feb, 2014 |
Pubmed ID: 24830246 The differences on chlorophyll fluorescence parameters, yield and water use efficiency of dryland maize were compared among full plastic film mulching on double ridges and planting in catchment furrows (FFDRF), half plastic film mulching on double ridges and planting in catchment furrows (HFDRF), plastic film mulching on ridge and planting in film-side (FS), and flat planting with no plastic film mulching (NM) under field conditions in dry highland of Loess Plateau in 2007-2012. The results showed that fluorescence yield (Fo), the maximum fluorescence yield (Fm), light-adapted fluorescence yield when PS II reaction centers were totally open (F), light-adapted fluorescence yield when PS II reaction centers closed (Fm'), the maximal photochemical efficiency of PS II (Fv/Fm), the actual photochemical efficiency of PS II in the light (Phi PS II), the relative electron transport rate (ETR), photochemical quenching (qP) and non-photochemical quenching (qN) in maize leaves of FFDRF were higher than that of control (NM), and the value of 1-qP was lower than that of control, at 13:00, chlorophyll fluorescence parameters values of FFDRF was significantly higher than control, which were increased by 5.3%, 56.8%, 10.7%, 36.3%, 23.6%, 56.7%, 64.4%, 45.5%, 23.6% and -55.6%, respectively, compared with the control. Yield and water use efficiency of FFDRF were the highest in every year no matter dry year, normal year, humid year and hail disaster year. Average yield and water use efficiency of FFDRF were 12,650 kg x hm(-2) and 40.4 kg x mm(-1) x hm(-2) during 2007-2012, increased by 57.8% and 61.6% compared with the control, respectively, and also significantly higher compared with HFDRF and PS. Therefore, it was concluded that FFDRF had significantly increased the efficiency of light energy conversion and improved the production capacity of dryland maize.
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Effect of Population Density on Reproduction in Microtus Fortis Under Laboratory Conditions
Acta Biologica Hungarica.
Jun, 2014 |
Pubmed ID: 24873906 Between December 2011 and March 2012, the reproductive characteristics of Microtus fortis reared in the laboratory at different population densities were assessed. In all, 258 male and female voles were randomly divided into 4 groups and reared at densities of 2, 4, 6, and 8 animals per cage (sex ratio: 1:1). The results showed that the pregnancy rate (χ2 = 21.671, df = 3, P < 0.001) and first farrowing interval (F = 12.355, df = 3, P < 0.001) were significantly different among the different population density groups, but the mean litter size (mean ± SD) was not (F = 2.669, df = 3, P > 0.05). In particular, the reproductive index and sex hormone levels showed a significant difference among the different density groups studied.
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Rural Residents in China Are at Increased Risk of Exposure to Tick-Borne Pathogens Anaplasma Phagocytophilum and Ehrlichia Chaffeensis
BioMed Research International.
2014 |
Pubmed ID: 24877080 As emerging tick born rickettsial diseases caused by A. phagocytophilum and E. chaffeensis, anaplasmosis and ehrlichiosis have become a serious threat to human and animal health throughout the world. In particular, in China, an unusual transmission of nosocomial cases of human granulocytic anaplasmosis occurred in Anhui Province in 2006 and more recent coinfection case of A. phagocytophilum and E. chaffeensis was documented in Shandong Province. Although the seroprevalence of human granulocytic anaplasmosis (former human granulocytic ehrlichiosis, HGE) has been documented in several studies, these data existed on local investigations, and also little data was reported on the seroprevalence of human monocytic ehrlichiosis (HME) in China. In this cross-sectional epidemiological study, indirect immunofluorescence antibody assay (IFA) proposed by WHO was used to detect A. phagocytophilum and E. chaffeensis IgG antibodies for 7,322 serum samples from agrarian residents from 9 provinces/cities and 819 urban residents from 2 provinces. Our data showed that farmers were at substantially increased risk of exposure. However, even among urban residents, risk was considerable. Seroprevalence of HGA and HME occurred in diverse regions of the country and tended to be the highest in young adults. Many species of ticks were confirmed carrying A. phagocytophilum organisms in China while several kinds of domestic animals including dog, goats, sheep, cattle, horse, wild rabbit, and some small wild rodents were proposed to be the reservoir hosts of A. phagocytophilum. The broad distribution of vector and hosts of the A. phagocytophilum and E. chaffeensis, especially the relationship between the generalized susceptibility of vectors and reservoirs and the severity of the disease's clinical manifestations and the genetic variation of Chinese HGA isolates in China, is urgently needed to be further investigated.
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Method to Control Depth Error when Ablating Human Dentin with Numerically Controlled Picosecond Laser: a Preliminary Study
Lasers in Medical Science.
Jun, 2014 |
Pubmed ID: 24890033 A three-axis numerically controlled picosecond laser was used to ablate dentin to investigate the quantitative relationships among the number of additive pulse layers in two-dimensional scans starting from the focal plane, step size along the normal of the focal plane (focal plane normal), and ablation depth error. A method to control the ablation depth error, suitable to control stepping along the focal plane normal, was preliminarily established. Twenty-four freshly removed mandibular first molars were cut transversely along the long axis of the crown and prepared as 48 tooth sample slices with approximately flat surfaces. Forty-two slices were used in the first section. The picosecond laser was 1,064 nm in wavelength, 3 W in power, and 10 kHz in repetition frequency. For a varying number (n = 5-70) of focal plane additive pulse layers (14 groups, three repetitions each), two-dimensional scanning and ablation were performed on the dentin regions of the tooth sample slices, which were fixed on the focal plane. The ablation depth, d, was measured, and the quantitative function between n and d was established. Six slices were used in the second section. The function was used to calculate and set the timing of stepwise increments, and the single-step size along the focal plane normal was d micrometer after ablation of n layers (n = 5-50; 10 groups, six repetitions each). Each sample underwent three-dimensional scanning and ablation to produce 2 × 2-mm square cavities. The difference, e, between the measured cavity depth and theoretical value was calculated, along with the difference, e 1, between the measured average ablation depth of a single-step along the focal plane normal and theoretical value. Values of n and d corresponding to the minimum values of e and e 1, respectively, were obtained. In two-dimensional ablation, d was largest (720.61 μm) when n = 65 and smallest when n = 5 (45.00 μm). Linear regression yielded the quantitative relationship: d = 10.547 × n - 7.5465 (R (2) = 0.9796). During three-dimensional ablation, e 1 was the smallest (0.02 μm) when n = 5 and d = 45.00 μm. The depth error was 1.91 μm when 450.00-μm depth cavities were produced. When ablating dentin with a three-axis picosecond laser scan-ablation device (450 μm, 3 W, 10 kHz), the number of focal plane additive pulse layers and step size along the focal plane normal was positively correlated with the single-layer and total ablation depth errors. By adjusting the timing of stepwise increments along the focal plane normal and single-step size when ablating dentin by using the numerically controlled picosecond laser, the single-step ablation depth error could be controlled at the micrometer level.
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Interleukin 17A Rs3819024 A>G Polymorphism is Associated with an Increased Risk of Gastric Cardia Adenocarcinoma in a Chinese Population
Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals.
Aug, 2014 |
Pubmed ID: 24893702 Gastric cardia adenocarcinoma (GCA) is one of the most common malignant tumors. In addition to environmental risk factors, genetic factors might play an important role in GCA carcinogenesis. To evaluate the association between polymorphisms in the interleukin 17A (IL17A) gene on the development of GCA, we conducted a hospital-based case-control study. A total of 243 GCA cases and 476 controls were recruited and their genotypes were determined using a custom-by-design 48-Plex SNPscan™ Kit. IL17A rs3819024 A > G polymorphism was found to be associated with the increased risk of GCA. When the IL17A rs3819024 AA homozygote genotype was used as the reference group, the AG genotype was associated with a significantly increased risk of GCA (AG versus AA: adjusted OR = 1.53, 95% CI = 1.05-2.23, p = 0.026). However, there was no significant association between five other SNPs and GCA. Stratified analyses indicated that a significantly increased risk of GCA associated with the IL17A rs3819024 A > G polymorphism was evident among male patients, patients who drank alcohol or those who never smoked. These findings indicated that functional polymorphism IL17A rs3819024 A > G might contribute to GCA susceptibility. Future larger studies with more rigorous study designs are required to confirm the current findings.
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Effects of Long-term Treatment with Quercetin on Cognition and Mitochondrial Function in a Mouse Model of Alzheimer's Disease
Neurochemical Research.
Aug, 2014 |
Pubmed ID: 24893798 Amyloid-β (Aβ)-induced mitochondrial dysfunction has been recognized as a prominent, early event in Alzheimer's disease (AD). Therefore, therapeutics targeted to improve mitochondrial function could be beneficial. Quercetin, a bioflavanoid, has been reported to have potent neuro-protective effects, but its preventive effects on Aβ-induced mitochondrial dysfunction and cognitive impairment have not been well characterised. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two quercetin (either 20 or 40 mg kg(-1) day(-1)) groups, or an Aricept (2 mg kg(-1) day(-1)) group. After 16 weeks of treatment, we observed beneficial effects of quercetin (40 mg kg(-1) day(-1)), including lessening learning and memory deficits, reducing scattered senile plaques, and ameliorating mitochondrial dysfunction, as evidenced by restoration of mitochondrial membrane potential, reactive oxygen species and ATP levels in mitochondria isolated from the hippocampus compared to control. Furthermore, the AMP-activated protein kinase (AMPK) activity significantly increased in the quercetin-treated (40 mg kg(-1) day(-1)) group. These findings suggest that a reduction in plaque burden and mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms by which quercetin improves cognitive functioning in the APPswe/PS1dE9 transgenic mouse model of AD.
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New Clustered Regularly Interspaced Short Palindromic Repeat Locus Spacer Pair Typing Method Based on the Newly Incorporated Spacer for Salmonella Enterica
Journal of Clinical Microbiology.
Aug, 2014 |
Pubmed ID: 24899040 A clustered regularly interspaced short palindromic repeat (CRISPR) typing method has recently been developed and used for typing and subtyping of Salmonella spp., but it is complicated and labor intensive because it has to analyze all spacers in two CRISPR loci. Here, we developed a more convenient and efficient method, namely, CRISPR locus spacer pair typing (CLSPT), which only needs to analyze the two newly incorporated spacers adjoining the leader array in the two CRISPR loci. We analyzed a CRISPR array of 82 strains belonging to 21 Salmonella serovars isolated from humans in different areas of China by using this new method. We also retrieved the newly incorporated spacers in each CRISPR locus of 537 Salmonella isolates which have definite serotypes in the Pasteur Institute's CRISPR Database to evaluate this method. Our findings showed that this new CLSPT method presents a high level of consistency (kappa = 0.9872, Matthew's correlation coefficient = 0.9712) with the results of traditional serotyping, and thus, it can also be used to predict serotypes of Salmonella spp. Moreover, this new method has a considerable discriminatory power (discriminatory index [DI] = 0.8145), comparable to those of multilocus sequence typing (DI = 0.8088) and conventional CRISPR typing (DI = 0.8684). Because CLSPT only costs about $5 to $10 per isolate, it is a much cheaper and more attractive method for subtyping of Salmonella isolates. In conclusion, this new method will provide considerable advantages over other molecular subtyping methods, and it may become a valuable epidemiologic tool for the surveillance of Salmonella infections.
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Time-intensity Curve Parameters in Rectal Cancer Measured Using Endorectal Ultrasonography with Sterile Coupling Gels Filling the Rectum: Correlations with Tumor Angiogenesis and Clinicopathological Features
BioMed Research International.
2014 |
Pubmed ID: 24900973 The primary aim of this study was to investigate the relationship between contrast-enhanced ultrasonography (CEUS) imaging parameters and clinicopathological features of rectal carcinoma and assess their potential as new radiological prognostic predictors. A total of 66 rectal carcinoma patients were analyzed with the time-intensity curve of CEUS. The parameter arrival time (AT), time to peak enhancement (TTP), wash-in time (WIT), enhanced intensity (EI), and ascending slope (AS) were measured. Microvessel density (MVD) was evaluated by immunohistochemical staining of surgical specimens. All findings were analysed prospectively and correlated with tumor staging, histological grading, and MVD. The mean values of AT, TTP, WIT, EI, and AS value of the rectal carcinoma were 10.84 ± 3.28 s, 20.61 ± 5.52 s, 9.78 ± 2.83 s, 28.68 ± 4.67 dB, and 3.20 ± 1.10, respectively. A positive linear correlation was found between the EI and MVD in rectal carcinoma (r = 0.295, P = 0.016), and there was a significant difference for EI among histological grading (r = -0.264, P = 0.007). EI decreased as T stage increased with a trend of association noted (P = 0.096). EI of contrast enhanced endorectal ultrasonography provides noninvasive biomarker of tumor angiogenesis in rectal cancer. CEUS data have the potential to predict patient prognosis.
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RNA-Seq Analysis of Yak Ovary: Improving Yak Gene Structure Information and Mining Reproduction-related Genes
Science China. Life Sciences.
Sep, 2014 |
Pubmed ID: 24907937 RNA-Seq, a high-throughput (HT) sequencing technique, has been used effectively in large-scale transcriptomic studies, and is particularly useful for improving gene structure information and mining of new genes. In this study, RNA-Seq HT technology was employed to analyze the transcriptome of yak ovary. After Illumina-Solexa deep sequencing, 26826516 clean reads with a total of 4828772880 bp were obtained from the ovary library. Alignment analysis showed that 16992 yak genes mapped to the yak genome and 3734 of these genes were involved in alternative splicing. Gene structure refinement analysis showed that 7340 genes that were annotated in the yak genome could be extended at the 5' or 3' ends based on the alignments been the transcripts and the genome sequence. Novel transcript prediction analysis identified 6321 new transcripts with lengths ranging from 180 to 14884 bp, and 2267 of them were predicted to code proteins. BLAST analysis of the new transcripts showed that 1200?4933 mapped to the non-redundant (nr), nucleotide (nt) and/or SwissProt sequence databases. Comparative statistical analysis of the new mapped transcripts showed that the majority of them were similar to genes in Bos taurus (41.4%), Bos grunniens mutus (33.0%), Ovis aries (6.3%), Homo sapiens (2.8%), Mus musculus (1.6%) and other species. Functional analysis showed that these expressed genes were involved in various Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes pathways. GO analysis of the new transcripts found that the largest proportion of them was associated with reproduction. The results of this study will provide a basis for describing the normal transcriptome map of yak ovary and for future studies on yak breeding performance. Moreover, the results confirmed that RNA-Seq HT technology is highly advantageous in improving gene structure information and mining of new genes, as well as in providing valuable data to expand the yak genome information.
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Correlation Between the Rupture Risk and 3D Geometric Parameters of Saccular Intracranial Aneurysms
Cell Biochemistry and Biophysics.
Jun, 2014 |
Pubmed ID: 24938901 The purpose of this study is to evaluate the association of the location and geometric parameters of intracranial aneurysm with the risk of rupture. A retrospective study consisted of 284 patients diagnosed with saccular intracranial aneurysm between January 2009 and May 2013 at Wuxi Third People's Hospital was conducted. 3D digital subtraction angiography images from all patients (240 ruptured, 44 unruptured) were obtained and analyzed. The location of the aneurysms and the 3D geometric parameters including the aneurysm depth, the neck size, diameter of the parent artery, aneurysm angle, aspect radio, size ratio, and the neck-to-parent-artery ratio (NPR) were compared between ruptured and unruptured groups. Results: In ruptured group, anterior communicating artery, posterior communicating artery (PCoA), and the bifurcation of internal carotid artery (ICA) were the top three locations for aneurysm occurrence, accounting for 40.00, 30.42, and 12.08 % respectively. While in the unruptured group, top three locations were PCoA (36.36 %), posterior cerebral circulation (18.18 %), and the bifurcation of the ICA (15.91 %). Distribution of aneurysm location is significantly different (p
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Protective Effects of Hyperbaric Oxygen Treatment Against Spinal Cord Injury in Rats Via Toll-like Receptor 2/nuclear Factor-κB Signaling
International Journal of Clinical and Experimental Pathology.
2014 |
Pubmed ID: 24966901 Spinal cord injury (SCI) is a serious medical problem with high mortality and disability rates. Hyperbaric oxygen (HBO) treatment is beneficial for neurological recovery after SCI, but the underlying mechanisms await characterization. This study examined whether HBO treatment following SCI in rats exerts a neuroprotective effect through activation of the toll-like receptor (TLR) 2/nuclear factor (NF)-κB signaling pathway. The SC of rats was injured via T10 laminectomy. Experimental animals (n=144) were divided into four groups: sham-operated (SH), SH+HBO, SCI, and SCI+HBO. Each group was subdivided into six subgroups (n=6 per group) that were examined at 12 h, and 1, 2, 3, 7, and 14 days post-injury. Functional recovery in the hind limb was evaluated using the Basso, Beattie, and Bresnahan (BBB) scoring system. The expression of TLR2 and NF-кB was assessed by real-time polymerase chain reaction and Western blotting, while interleukin-1 (IL)-1β and tumor necrosis factor (TNF)-α levels were measured by enzyme-linked immunosorbent assay. TLR2 and NF-кB levels and histological scores were higher in the SCI than in the SH and SH+HBO groups at various time points. HBO treatment decreased TLR2 and NF-кB expression and histological scores as well as IL-1β and TNF-α levels compared to the SCI group at early post-injury stages. In addition, BBB scores were improved in the SCI+HBO relative to the SCI group at 7 and 14 days. HBO treatment may mitigate secondary injury to the SC by inhibiting inflammatory responses induced by TLR2/NF-кB signaling, thereby promoting functional recovery and improving neurological outcome.
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PolyUbiquitin Chain Linkage Topology Selects the Functions from the Underlying Binding Landscape
PLoS Computational Biology.
Jul, 2014 |
Pubmed ID: 24992446 Ubiquitin (Ub) can generate versatile molecular signals and lead to different celluar fates. The functional poly-valence of Ub is believed to be resulted from its ability to form distinct polymerized chains with eight linkage types. To provide a full picture of ubiquitin code, we explore the binding landscape of two free Ub monomers and also the functional landscapes of of all eight linkage types by theoretical modeling. Remarkably, we found that most of the compact structures of covalently connected dimeric Ub chains (diUbs) pre-exist on the binding landscape. These compact functional states were subsequently validated by corresponding linkage models. This leads to the proposal that the folding architecture of Ub monomer has encoded all functional states into its binding landscape, which is further selected by different topologies of polymeric Ub chains. Moreover, our results revealed that covalent linkage leads to symmetry breaking of interfacial interactions. We further propose that topological constraint not only limits the conformational space for effective switching between functional states, but also selects the local interactions for realizing the corresponding biological function. Therefore, the topological constraint provides a way for breaking the binding symmetry and reaching the functional specificity. The simulation results also provide several predictions that qualitatively and quantitatively consistent with experiments. Importantly, the K48 linkage model successfully predicted intermediate states. The resulting multi-state energy landscape was further employed to reconcile the seemingly contradictory experimental data on the conformational equilibrium of K48-diUb. Our results further suggest that hydrophobic interactions are dominant in the functional landscapes of K6-, K11-, K33- and K48 diUbs, while electrostatic interactions play a more important role in the functional landscapes of K27, K29, K63 and linear linkages.
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Formononetin Mediates Neuroprotection Against Cerebral Ischemia/reperfusion in Rats Via Downregulation of the Bax/Bcl-2 Ratio and Upregulation PI3K/Akt Signaling Pathway
Journal of the Neurological Sciences.
Sep, 2014 |
Pubmed ID: 24996490 Isoflavone formononetin is a typical phytoestrogen isolated from Chinese medical herb red clover. It has been reported that estrogens have neuroprotective properties, and dietary intake of phytoestrogens could reduce stroke injury in cerebral ischemia/reperfusion (I/R) animal models. In the present research, we sought to investigate the molecular mechanisms underlying the neuroprotective effects of formononetin on I/R rats. Male Sprague-Dawley rats were subjected to a 2h period of right middle cerebral artery occlusion (MCAO) followed by 24h of reperfusion. Then neurological deficits and brain edema were evaluated. To provide insight into the functions of phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK (mitogen-activated protein kinase) signaling pathway in formononetin-induced neuroprotection, the expression of ER-α, Bax, Bcl-2, p-Akt (phosphorylated protein kinase B), and p-ERK1/2 (phosphorylated extracellular signal-regulated kinases 1/2) was determined by qPCR or Western blot assay. Consequently, we found that formononetin has significantly reduced the infarcted volume and the brain water content, and improved the neurological deficit. Formononetin also exhibited an upregulation in ER-α and p-Akt, a downregulation in the ratio of Bax/Bcl-2. However, formononetin had little effect on p-ERK1/2 proteins expression. Taken together, formononetin has shown neuroprotective effects in cerebral I/R rats, and the molecular mechanisms may correlate with the downregulation of the Bax/Bcl-2 ratio and the activation of PI3K/Akt signaling pathway.
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Updating Biomass into Functional Carbon Material in Ionothermal Manner
ACS Applied Materials & Interfaces.
Aug, 2014 |
Pubmed ID: 25001196 The development of meaningful ways to transfer biomass into useful materials, more efficient energy carriers, and/or carbon storage deposits is a profound challenge of our days. Herein, an ionothermal carbonization (ITC) method, via treating natural resources (glucose, cellulose, and sugar cane bagesse) in nonmetal ionic liquids (ILs) at ∼200 °C, is established for the fabrication of porous heteroatom-doped carbon materials with high yield. Commercial ILs with bulky bis(trifluoromethylsulfonyl)imide anion or cross-linkable nitrile group were found to be efficient and recyclable templates for porosity control, leading to exciting nanoarchitectures with promising performance in oxygen reduction reaction. The optimized ILs (12 mL) can dissolve and directly convert up to 15 g of glucose into porous carbon materials (SBET: 272 m(2)/g) one time. This ITC method relies on the synergistic use of structure-directing effect, good biomass solubility, and excellent thermal stability of ILs, and provides a sustainable strategy for exploiting biomass.
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Molybdenum Disulfide Quantum Dots As a Photoluminescence Sensing Platform for 2,4,6-trinitrophenol Detection
Analytical Chemistry.
Aug, 2014 |
Pubmed ID: 25001878 Transition metal chalcogenides, especially molybdenum disulfide (MoS2), have recently attracted wide attention from researchers as graphene-analogous materials. However, until now, little literature has reported the synthesis of photoluminescent MoS2 materials and their applications in analytical chemistry. We herein presented a facile bottom-up hydrothermal route for the synthesis of photoluminescent MoS2 quantum dots (QDs) by using sodium molybdate and cysteine as precursors. The prepared MoS2 QDs were characterized by transmission electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, photoluminescence spectroscopy, and UV-vis spectroscopy. The MoS2 QDs were then used as photoluminescent probes to construct a photoluminescence (PL) quenching sensor for detection of 2,4,6-trinitrophenol (TNP). The TNP sensor presented a wide linear range from 0.099 to 36.5 μM with a high detection limit of 95 nM. Furthermore, the sensor displayed a high sensitivity toward TNP over other structurally similar compounds like 2,4,6-trinitrotoluene, p-chlorophenol, phenol, and 2,6-di-tert-butyl-4-methylphenol. To understand the origin of the high sensitivity, we assessed the emission wavelength-dependent PL quenching behavior of MoS2 QDs by the above five compounds using Stem-Volmer equation in detail. The results showed that the novel approach we put forward can satisfactorily explain the interaction mechanisms between MoS2 QDs and the five compounds, and the high sensitivity for TNP very likely originated from a combination of the PL resonance energy transfer, electronic energy transfer, and electrostatic interactions between MoS2 QDs and TNP. Finally, the sensor was successfully applied for detection of TNP in water samples and test papers.
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Quantifying White Matter Tract Diffusion Parameters in the Presence of Increased Extra-fiber Cellularity and Vasogenic Edema
NeuroImage.
Nov, 2014 |
Pubmed ID: 25017446 The effect of extra-fiber structural and pathological components confounding diffusion tensor imaging (DTI) computation was quantitatively investigated using data generated by both Monte-Carlo simulations and tissue phantoms. Increased extent of vasogenic edema, by addition of various amount of gel to fixed normal mouse trigeminal nerves or by increasing non-restricted isotropic diffusion tensor components in Monte-Carlo simulations, significantly decreased fractional anisotropy (FA) and increased radial diffusivity, while less significantly increased axial diffusivity derived by DTI. Increased cellularity, mimicked by graded increase of the restricted isotropic diffusion tensor component in Monte-Carlo simulations, significantly decreased FA and axial diffusivity with limited impact on radial diffusivity derived by DTI. The MC simulation and tissue phantom data were also analyzed by the recently developed diffusion basis spectrum imaging (DBSI) to simultaneously distinguish and quantify the axon/myelin integrity and extra-fiber diffusion components. Results showed that increased cellularity or vasogenic edema did not affect the DBSI-derived fiber FA, axial or radial diffusivity. Importantly, the extent of extra-fiber cellularity and edema estimated by DBSI correlated with experimentally added gel and Monte-Carlo simulations. We also examined the feasibility of applying 25-direction diffusion encoding scheme for DBSI analysis on coherent white matter tracts. Results from both phantom experiments and simulations suggested that the 25-direction diffusion scheme provided comparable DBSI estimation of both fiber diffusion parameters and extra-fiber cellularity/edema extent as those by 99-direction scheme. An in vivo 25-direction DBSI analysis was performed on experimental autoimmune encephalomyelitis (EAE, an animal model of human multiple sclerosis) optic nerve as an example to examine the validity of derived DBSI parameters with post-imaging immunohistochemistry verification. Results support that in vivo DBSI using 25-direction diffusion scheme correctly reflect the underlying axonal injury, demyelination, and inflammation of optic nerves in EAE mice.
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Heterogeneity Research in Muscle-invasive Bladder Cancer Based on Differential Protein Expression Analysis
Medical Oncology (Northwood, London, England).
Sep, 2014 |
Pubmed ID: 25085780 The aim of this study was to study the expression profiles of muscle-invasive bladder cancer (MIBC) cells of different risk groups and to explore the crucial role of biological pathway change in heterogeneity of MIBC cells. Thirty individual samples (cancer and non-cancerous specimens) were obtained from patients with MIBC. Laser capture microdissection was employed to harvest the homogeneous MIBC cells and normal urothelial cells. iTRAQ and 2D-LC-MS/MS were used to quantify and identify the differently expressed proteins. Then, the significantly changed proteins were further analyzed using Arraytrack ™ software. The interested proteins were compared with the published literatures to discuss the exact functions. A total of 3,073 non-redundant proteins were identified in this research; therefore, 855/2,210/633 (fold change >1.5 relative to normal group) presented in high-/median-/low-risk groups, respectively. 617/1,620/463 proteins with SWISS-ACC number output from Arraytrack ™ software and presented in high-/median-/low-risk groups, respectively. Pathway analysis revealed that the mainly changed pathways (top-10, p < 0.05) in Genetic information processing category were similar in high- and median-risk groups, including Kyoto Encyclopedia of Genes and Genomes (KEGG) spliceosome, protein export, ribosome pathways. The mainly altered pathways in Metabolism category included glycolysis/gluconeogenesis, pentose phosphate, pyruvate metabolism pathway for high-risk group, and glutathione metabolism, citrate cycle, oxidative phosphorylation pathways for median-risk group. The major changed pathways for low-risk group included focal adhesion pathway and ECM-receptor interaction pathway. The changed biological pathways are closely related to the regulation of heterogeneity for MIBC. The KEGG pathways of Genetic information processing category and Metabolism (anaerobic or aerobic) category play a crucial role in determining the malignant phenotype of MIBC cells. The quantification analysis of proteins combining with the KEGG pathway analysis contributes to screening candidate biomarkers and guides the biological molecular therapy of MIBC.
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Complete Mitochondrial Genome of Paramisgurnus Dabryanus
Mitochondrial DNA.
Aug, 2014 |
Pubmed ID: 25090380 Abstract In this study, the complete mitochondrial genome of Paramisgurnus dabryanus was obtained by PCR base on 18 pairs of primers. Among the 18 primers, the 14 primers were from the previously published universal primers for Cyprinus carpio L. mitogenome amplification. The remaining 4 primers were designed on the basis of related species mtDNA sequences. The genome is 16,570 bp in length, including 2 ribosomal RNA genes. 13 proteins-coding genes, 22 transfer RNA genes, and a non-coding control region, the gene composition and order of which was similar to most reported from other vertebrates. Sequence analysis showed that the overall base composition of Paramisgurnus dabryanus is T 27.3%, C 26.9%, A 28.5%, and G 17.4%. The sequence is a slight A + T bias of 55.8%, which is similar to other fishes. Mitochondrial genome is widely used in phylogenetic analysis, evolutionary genomics, species identification and related research of fish.
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A New Species of Scytalidium Causing Slippery Scar on Cultivated Auricularia Polytricha in China
FEMS Microbiology Letters.
Aug, 2014 |
Pubmed ID: 25091557 Slippery scar is one of the most destructive diseases encountered in the cultivation of Auricularia polytricha (hairy wood ear); however, the identity of the pathogenic agent has remained uncertain. This study was designed to identify the causative pathogen of slippery scar in A. polytricha and to investigate the taxonomic classification of the pathogen by morphological observations, in vivo pathogenicity tests, and molecular evidences of ITS and RPB2 sequences. The results showed that the pathogen was a new Scytalidium species, here named Scytalidium auriculariicola. Scytalidium auriculariicola was characterized by its rapid growth rate, the catenate conidia of variable size, and the pale brown to brown chlamydoconidia. Phylogenetic analyses based on internal transcribed spacer regions and RPB2 sequences on the pathogen isolated and related species supported that S. auriculariicola was a true Scytalidium species. It was congeneric with and close to Scytalidium lignicola, the type species of Scytalidium. However, it differed from the latter species in the size of conidia, 33 different nucleotide bases in ITS sequences and 30 different nucleotide bases in RPB2 sequences.
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MOMMOP: Multiobjective Optimization for Locating Multiple Optimal Solutions of Multimodal Optimization Problems
IEEE Transactions on Cybernetics.
Aug, 2014 |
Pubmed ID: 25099966 In the field of evolutionary computation, there has been a growing interest in applying evolutionary algorithms to solve multimodal optimization problems (MMOPs). Due to the fact that an MMOP involves multiple optimal solutions, many niching methods have been suggested and incorporated into evolutionary algorithms for locating such optimal solutions in a single run. In this paper, we propose a novel transformation technique based on multiobjective optimization for MMOPs, called MOMMOP. MOMMOP transforms an MMOP into a multiobjective optimization problem with two conflicting objectives. After the above transformation, all the optimal solutions of an MMOP become the Pareto optimal solutions of the transformed problem. Thus, multiobjective evolutionary algorithms can be readily applied to find a set of representative Pareto optimal solutions of the transformed problem, and as a result, multiple optimal solutions of the original MMOP could also be simultaneously located in a single run. In principle, MOMMOP is an implicit niching method. In this paper, we also discuss two issues in MOMMOP and introduce two new comparison criteria. MOMMOP has been used to solve 20 multimodal benchmark test functions, after combining with nondominated sorting and differential evolution. Systematic experiments have indicated that MOMMOP outperforms a number of methods for multimodal optimization, including four recent methods at the 2013 IEEE Congress on Evolutionary Computation, four state-of-the-art single-objective optimization based methods, and two well-known multiobjective optimization based approaches.
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Transmission Characteristics of Different Students During a School Outbreak of (H1N1) Pdm09 Influenza in China, 2009
Scientific Reports.
2014 |
Pubmed ID: 25102240 Many outbreaks of A(H1N1)pdm09 influenza have occurred in schools with a high population density. Containment of school outbreaks is predicted to help mitigate pandemic influenza. Understanding disease transmission characteristics within the school setting is critical to implementing effective control measures. Based on a school outbreak survey, we found almost all (93.7%) disease transmission occurred within a single grade, only 6.3% crossed grades. Transmissions originating from freshmen exhibited a star-shaped network; other grades exhibited branch- or line-shaped networks, indicating freshmen have higher activity and are more likely to cause infection. R0 for freshmen, calculated as 2.04, estimated as 2.76, was greater than for other grades (P < 0.01). Without intervention, the estimated number of cases was much greater when the outbreak was initiated by freshmen than by other grades. Furthermore, the estimated number of cases required to be under quarantine and isolation for freshmen was less than that of equivalent other grades. So we concluded that different grades have different transmission mode. Freshmen were the main facilitators of the spread of A(H1N1)pdm09 influenza during this school outbreak, so control measures (e.g. close contact isolation) priority used for freshmen would likely have effectively reduced spread of influenza in school settings.
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Single Molecule Investigation of Ag+ Interactions with Single Cytosine-, Methylcytosine- and Hydroxymethylcytosine-cytosine Mismatches in a Nanopore
Scientific Reports.
2014 |
Pubmed ID: 25103463 Both cytosine-Ag-cytosine interactions and cytosine modifications in a DNA duplex have attracted great interest for research. Cytosine (C) modifications such as methylcytosine (mC) and hydroxymethylcytosine (hmC) are associated with tumorigenesis. However, a method for directly discriminating C, mC and hmC bases without labeling, modification and amplification is still missing. Additionally, the nature of coordination of Ag(+) with cytosine-cytosine (C-C) mismatches is not clearly understood. Utilizing the alpha-hemolysin nanopore, we show that in the presence of Ag(+), duplex stability is most increased for the cytosine-cytosine (C-C) pair, followed by the cytosine-methylcytosine (C-mC) pair, and the cytosine-hydroxymethylcytosine (C-hmC) pair, which has no observable Ag(+) induced stabilization. Molecular dynamics simulations reveal that the hydrogen-bond-mediated paring of a C-C mismatch results in a binding site for Ag(+). Cytosine modifications (such as mC and hmC) disrupted the hydrogen bond, resulting in disruption of the Ag(+) binding site. Our experimental method provides a novel platform to study the metal ion-DNA interactions and could also serve as a direct detection method for nucleobase modifications.
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The Antidiabetic Agent Glibenclamide Protects Airway Hyperresponsiveness and Inflammation in Mice
Inflammation.
Aug, 2014 |
Pubmed ID: 25113133 Glibenclamide has a newly discovered role in inflammation regulation besides its antidiabetic effect. As an inhibitor of ATP-sensitive potassium (KATP) channel, glibenclamide antagonizes the relaxation of the tracheal smooth muscle. This indicates that glibenclamide might attenuate airway inflammation while aggravate airway hyperresponsiveness (AHR) in asthmatics. Clinically, many diabetics with asthma are prescribed with glibenclamide to control blood glucose. However, whether glibenclamide could exert any effects on asthmatic inflammation remains unknown. Using an ovalbumin (OVA)-induced mouse model of asthma, we evaluated the effects of glibenclamide on the AHR and inflammation. Interestingly, glibenclamide reduced all the cardinal features of asthma in OVA-challenged mice, including AHR, airway inflammation, and T-helper type 2 (Th2) cytokines. Glibenclamide also downregulated OVA-induced expressions of vascular cell adhesion molecule 1 (VCAM-1) and phosphorylated signal transducer and activator of transcription 6 (p-STAT6) in the lung. In addition, increased sulfonylurea receptor 1 (SUR1) expression in the lung was observed after the OVA challenge. These findings suggest that the classic sulfonylurea glibenclamide plays an important protective role in the development of asthma, which not only provides the evidence for the safety of prescribed glibenclamide in diabetics combined with asthma but also indicates a possible new therapeutic for asthma via targeting glibenclamide-related pathways.
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ABCB1 C3435T Polymorphism and the Risk of Ischemic Heart Disease: A Meta-Analysis
Genetic Testing and Molecular Biomarkers.
Sep, 2014 |
Pubmed ID: 25118983 ATP binding cassette transporter 1 (ABCB1) plays a critical role in the development and progression of cardiovascular disease. Emerging evidence suggests that common functional polymorphisms in the ABCB1 gene might have an impact on an individual's susceptibility to ischemic heart disease, but individually published results are inconclusive. The MEDLINE (1966-2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013), and the Chinese Biomedical Database (CBM; 1982-2013) were searched without language restrictions. Meta-analysis was performed with the use of the STATA statistical software. Odds ratios (OR) with their 95% confidence intervals (95% CIs) were calculated. Seven case-control studies with a total of 2310 myocardial infarction (MI) patients and 10,506 acute coronary syndrome (ACS) patients met the inclusion criteria. Our meta-analysis results indicated that ABCB1 C3435T polymorphism may be associated with an increased risk of MI and ACS, especially among Asian populations (T allele vs. C allele: OR=1.40, 95% CI=1.31-1.49, ph=0.058). Meta-regression analyses showed that clinical subtype and ethnicity may be the main sources of heterogeneity (T allele vs. C allele: OR=1.16, 95% CI=0.97-1.37, ph=0.036). Our findings provide empirical evidence that ABCB1 C3435T polymorphism may contribute to the risk of MI and ACS, especially among Caucasian populations. Thus, detection of ABCB1 C3435T polymorphism may be a promising biomarker for the early detection of MI and ACS.
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Development and Cross-validation of Prognostic Models to Assess the Treatment Effect of Cisplatin/pemetrexed Chemotherapy in Lung Adenocarcinoma Patients
Medical Oncology (Northwood, London, England).
Sep, 2014 |
Pubmed ID: 25119500 Better understanding of the treatment effect of cisplatin/pemetrexed chemotherapy on lung adenocarcinoma patients is needed to facilitate chemotherapy planning and patient care. In this retrospective study, we will develop prognostic models by the cross-validation method using clinical and serum factors to predict outcomes of cisplatin/pemetrexed chemotherapy in lung adenocarcinoma patients. Lung adenocarcinoma patients admitted between 2008 and 2013 were enrolled. 29 serum parameters of laboratory tests and 14 clinical factors were analyzed to develop the prognostic models. First, the stepwise selection and five-fold cross-validation were performed to identify candidate prognostic factors. Then a classification of all patients based on the number of metastatic sites resulted in four distinct subsets. In each subset, a prognostic model was fitted with the most accurate prognostic factors from the candidate prognostic factors. Categorical survival prediction was estimated using a log-rank test and visualized with Kaplan-Meier method. 227 lung adenocarcinoma patients were enrolled. Twenty candidate prognostic factors evaluated using the five-fold cross-validation method were total protein, total bilirubin, direct bilirubin, creatine kinase, age, smoking index, neuron-specific enolase, bone metastasis, total triglyceride, albumin, gender, uric acid, CYFRA21-1, lymph node metastasis, liver metastasis, lactate dehydrogenase, CA153, peritoneal metastasis, CA125, and CA199. From these 20 candidate prognostic factors, the multivariate Cox proportional hazard model with the highest prognostic accuracy in each subset was identified by the stepwise forward selection method, which generated significant prognostic stratifications in Kaplan-Meier survival analyses (all log-rank p < 0.01). Generally, the prognostic models using five-fold cross-validation achieve a good prediction performance. The prognostic models can be administered safely to lung adenocarcinoma patients treated with first-line cisplatin/pemetrexed chemotherapy, and a comprehensive assessment of clinical and serum factors helps predict the outcomes of cisplatin/pemetrexed chemotherapy.
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Non-random Escape Pathways from a Broadly Neutralizing Human Monoclonal Antibody Map to a Highly Conserved Region on the Hepatitis C Virus E2 Glycoprotein Encompassing Amino Acids 412-423
PLoS Pathogens.
Aug, 2014 |
Pubmed ID: 25122476 A challenge for hepatitis C virus (HCV) vaccine development is to define epitopes that are able to elicit protective antibodies against this highly diverse virus. The E2 glycoprotein region located at residues 412-423 is conserved and antibodies to 412-423 have broadly neutralizing activities. However, an adaptive mutation, N417S, is associated with a glycan shift in a variant that cannot be neutralized by a murine but by human monoclonal antibodies (HMAbs) against 412-423. To determine whether HCV escapes from these antibodies, we analyzed variants that emerged when cell culture infectious HCV virions (HCVcc) were passaged under increasing concentrations of a specific HMAb, HC33.1. Multiple nonrandom escape pathways were identified. Two pathways occurred in the context of an N-glycan shift mutation at N417T. At low antibody concentrations, substitutions of two residues outside of the epitope, N434D and K610R, led to variants having improved in vitro viral fitness and reduced sensitivity to HC33.1 binding and neutralization. At moderate concentrations, a S419N mutation occurred within 412-423 in escape variants that have greatly reduced sensitivity to HC33.1 but compromised viral fitness. Importantly, the variants generated from these pathways differed in their stability. N434D and K610R-associated variants were stable and became dominant as the virions were passaged. The S419N mutation reverted back to N419S when immune pressure was reduced by removing HC33.1. At high antibody concentrations, a mutation at L413I was observed in variants that were resistant to HC33.1 neutralization. Collectively, the combination of multiple escape pathways enabled the virus to persist under a wide range of antibody concentrations. Moreover, these findings pose a different challenge to vaccine development beyond the identification of highly conserved epitopes. It will be necessary for a vaccine to induce high potency antibodies that prevent the formation of escape variants, which can co-exist with lower potency or levels of neutralizing activities.
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Hesperidin Alleviates Cognitive Impairment, Mitochondrial Dysfunction and Oxidative Stress in a Mouse Model of Alzheimer's Disease
Cellular and Molecular Neurobiology.
Aug, 2014 |
Pubmed ID: 25135708 The role of mitochondrial dysfunction and oxidative stress has been well-documented in Alzheimer's disease (AD). Bioflavonoids are being utilised as neuroprotectants in the treatment of various neurological disorders, including AD. Therefore, we conducted this current study in order to explore the effects of hesperidin (a flavanone glycoside) against amyloid-β (Aβ)-induced cognitive dysfunction, oxidative damage and mitochondrial dysfunction in mice. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two hesperidin (either 50 or 100 mg/kg per day) groups, or an Aricept (2.5 mg/kg per day) group. After 16 weeks of treatment, although there was no obvious change in Aβ deposition in the hesperidin-treated (100 mg/kg per day) group, however, we found that the administration of hesperidin (100 mg/kg per day) resulted in the reduction of learning and memory deficits, improved locomotor activity, and the increase of anti-oxidative defense and mitochondrial complex I-IV enzymes activities. Furthermore, Glycogen synthase kinase-3β (GSK-3β) phosphorylation significantly increased in the hesperidin-treated (100 mg/kg per day) group. Taken together, these findings suggest that a reduction in mitochondrial dysfunction through the inhibition of GSK-3β activity, coupled with an increase in anti-oxidative defense, may be one of the mechanisms by which hesperidin improves cognitive function in the APPswe/PS1dE9 transgenic mouse model of AD.
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Identification of MiRNAs As Potential New Biomarkers for Nervous System Cancer
Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine.
Aug, 2014 |
Pubmed ID: 25139093 Several recent studies have indicated the possibility of detecting dysregulated microRNAs (miRNAs) to diagnose nervous system cancer (NSC). Our study was conducted to explore the clinical applicability of miRNAs as potential ideal biomarkers for the diagnosis of NSC. For this meta-analysis, a systematic literature search was conducted in the Embase, Medline, Cochrane, Wangfang, and Sinomed databases. A standard quality tool-quality assessment of diagnostic accuracy studies was employed to assess the quality of the included studies. Specificity, sensitivity, diagnostic odds ratio (DOR), and area under curve (AUC) were pooled to assess overall test accuracy. In total, 25 studies from 7 articles, including 388 patients with NSC and 435 controls (healthy controls and patients with neurologic disorders), were included in this meta-analysis. For the studied miRNAs, the pooled sensitivity, specificity, and DOR for predicting NSC were 85 % (95 % confidence interval [CI] 80-89 %), 85 % (95 % CI 80-89 %), and 32 (95 % CI 19-55), respectively. The pooled AUC for miRNAs identifying NSC was 0.92. In addition, results from subgroup analyses indicated that using miRNA panels yield a much better diagnostic accuracy when compared with using a particular miRNA. The current evidence suggests that miRNAs, especially miRNA panels on body fluids, may be suitable for use as diagnostic biomarkers for NSC patients. However, more prospective studies using larger cohorts should be conducted to confirm their degree of accuracy.
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Enamel Organic Matrix: Potential Structural Role in Enamel and Relationship to Residual Basement Membrane Constituents at the Dentin Enamel Junction
Connective Tissue Research.
Aug, 2014 |
Pubmed ID: 25158177 Abstract Although mature enamel is predominantly composed of mineral, a previously uncharacterized organic matrix layer remains in the post-eruptive tissue that begins at the dentin enamel junction and extends 200-300 μm towards the outer tooth surface. Identification of the composition of this layer has been hampered by its insolubility; however, we have developed a single step method to isolate the organic enamel matrix relatively intact. After dissociative dissolution of the matrix with SDS and urea, initial characterization by Western blotting and gel zymography indicates the presence of type IV and type VII basement membrane collagens and active matrix metalloproteinase-20. When combined with data from transgenic knockout mice and from human mutations, these data suggest that the enamel organic matrix (EOM) and dentin enamel junction may have a structural and functional relationship with basement membranes, e.g. skin. To clarify this relationship, we hypothesize a "foundation" model which proposes that components of the EOM form a support structure that stabilizes the crystalline enamel layer, and bonds it to the underlying dentin along the dentin enamel junction. Since we have also co-localized an active matrix metalloproteinase to this layer, our hypothesis suggests that, under pathologic conditions, MMP-mediated degradation of the EOM could destabilize the enamel-dentin interface.
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Theoretical Insights into the Reductive Metabolism of CCl4 by Cytochrome P450 Enzymes and the CCl4-dependent Suicidal Inactivation of P450
Dalton Transactions (Cambridge, England : 2003).
Sep, 2014 |
Pubmed ID: 25164482 The anaerobic metabolism of CCl4 by P450 enzymes was investigated using quantum chemical calculations. It was found that under anaerobic conditions, the substrate CCl4 might undergo one or two subsequent one-electron reductions to generate different reactive metabolites, trichloromethyl radical (˙CCl3) and dichlorocarbene (:CCl2) respectively. Meanwhile, it was the reduced ferrous haem complex rather than the unreduced ferric haem complex that could directly achieve such reductions. Based on the formation of the former reactive metabolite, a further one-electron reduction could take place with the assistance of a proton to yield the latter reactive species, i.e., a further reductive dechloridation of ˙CCl3 could take place via a novel SE3 mechanism. In addition, the ˙CCl3 species was capable of binding covalently to the meso-carbon atom of the prosthetic group, leading to the suicidal destruction of P450 enzymes. Whereas the :CCl2 species was involved in the CCl4-dependent reversible P450 inhibition as its hydrolysis product, CO, but was not significantly involved in the CCl4-dependent irreversible P450 destruction. It is obvious that the reductive metabolism of CCl4 to reactive intermediates by P450 enzymes is an essential prerequisite for its toxicity.
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The Genetic Prehistory of the New World Arctic
Science (New York, N.Y.).
Aug, 2014 |
Pubmed ID: 25170159 The New World Arctic, the last region of the Americas to be populated by humans, has a relatively well-researched archaeology, but an understanding of its genetic history is lacking. We present genome-wide sequence data from ancient and present-day humans from Greenland, Arctic Canada, Alaska, Aleutian Islands, and Siberia. We show that Paleo-Eskimos (~3000 BCE to 1300 CE) represent a migration pulse into the Americas independent of both Native American and Inuit expansions. Furthermore, the genetic continuity characterizing the Paleo-Eskimo period was interrupted by the arrival of a new population, representing the ancestors of present-day Inuit, with evidence of past gene flow between these lineages. Despite periodic abandonment of major Arctic regions, a single Paleo-Eskimo metapopulation likely survived in near-isolation for more than 4000 years, only to vanish around 700 years ago.
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Dynamic Conformational Change Regulates the Protein-DNA Recognition: An Investigation on Binding of a Y-Family Polymerase to Its Target DNA
PLoS Computational Biology.
Sep, 2014 |
Pubmed ID: 25188490 Protein-DNA recognition is a central biological process that governs the life of cells. A protein will often undergo a conformational transition to form the functional complex with its target DNA. The protein conformational dynamics are expected to contribute to the stability and specificity of DNA recognition and therefore may control the functional activity of the protein-DNA complex. Understanding how the conformational dynamics influences the protein-DNA recognition is still challenging. Here, we developed a two-basin structure-based model to explore functional dynamics in Sulfolobus solfataricus DNA Y-family polymerase IV (DPO4) during its binding to DNA. With explicit consideration of non-specific and specific interactions between DPO4 and DNA, we found that DPO4-DNA recognition is comprised of first 3D diffusion, then a short-range adjustment sliding on DNA and finally specific binding. Interestingly, we found that DPO4 is under a conformational equilibrium between multiple states during the binding process and the distributions of the conformations vary at different binding stages. By modulating the strength of the electrostatic interactions, the flexibility of the linker, and the conformational dynamics in DPO4, we drew a clear picture on how DPO4 dynamically regulates the DNA recognition. We argue that the unique features of flexibility and conformational dynamics in DPO4-DNA recognition have direct implications for low-fidelity translesion DNA synthesis, most of which is found to be accomplished by the Y-family DNA polymerases. Our results help complete the description of the DNA synthesis process for the Y-family polymerases. Furthermore, the methods developed here can be widely applied for future investigations on how various proteins recognize and bind specific DNA substrates.
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Wettability of Dentin After Yb:KYW Thin-disk Femtosecond Ablation
Lasers in Medical Science.
Sep, 2014 |
Pubmed ID: 25213830 The aim of this study was to quantitatively evaluate the wettability of dentin after Yb:KYW thin-disk femtosecond-pulsed laser ablation by measuring the contact angle. Different laser parameters were used including different fluences (F), scanning speeds, and scanning line spacings. Crowns of 15 extracted human teeth were cut longitudinally into slices approximately 1.5-mm thick with a cutting instrument. The samples were randomly divided into ten groups (n = 3/group). Samples in groups 1-8 were irradiated with a femtosecond-pulsed laser. The dentin samples were fixed on a stage at the focal plane, and the laser beam irradiated the samples through a galvanometric scanning system so rectangular movement could be achieved. Samples in groups 9 and 10 were prepared with grinding instruments. Following ablation and preparation, the samples were examined for contact angle with an optical contact angle measuring instrument. The results showed that scanning speed and scanning line spacing had little influence on the wettability of dentin following femtosecond-pulsed laser ablation, except when F = 6 J/cm(2). For six out of the eight laser ablation groups, when a lower fluence was used, the dentin contact angle was higher and vice versa. Most of the dentin which had been ablated using the femtosecond-pulsed laser had improved wettability compared to samples prepared with the grinding instruments. This study showed that various laser fluences, scanning speeds, and scanning line spacings can alter dentin wettability. Therefore, adequate parameters should be chosen to achieve proper therapeutic benefits.
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LY2875358, A Neutralizing and Internalizing Anti-MET Bivalent Antibody, Inhibits HGF-Dependent and HGF-Independent MET Activation and Tumor Growth
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research.
Sep, 2014 |
Pubmed ID: 25231402 Background: MET, the receptor for hepatocyte growth factor (HGF), has been implicated in driving tumor proliferation and metastasis. High MET expression is correlated with poor prognosis in multiple cancers. Activation of MET can be induced either by HGF-independent mechanisms such as gene amplification, specific genetic mutations, and transcriptional up-regulation; or by HGF-dependent autocrine or paracrine mechanisms. Methods / Results: Here we report on LY2875358, a novel humanized bivalent anti-MET antibody that has high neutralization and internalization activities resulting in inhibition of both HGF-dependent and HGF-independent MET pathway activation and tumor growth. In contrast to other bivalent MET antibodies, LY2875358 exhibits no functional agonist activity and does not stimulate biological activities such as cell proliferation, scattering, invasion, tubulogenesis, or apoptosis protection in various HGF-responsive cells, and no evidence of inducing proliferation in vivo in a monkey toxicity study. LY2875358 blocks HGF binding to MET and HGF-induced MET phosphorylation and cell proliferation. In contrast to the humanized one-armed 5D5 anti-MET antibody, LY2875358 induces internalization and degradation of MET that inhibits cell proliferation and tumor growth in models where MET is constitutively activated. Moreover, LY2875358 has potent antitumor activity in both HGF-dependent and HGF-independent (MET amplified) xenograft tumor models. Together, these findings indicate that the mechanism of action of LY2875358 is different than that of the one-armed MET antibody. Conclusions: LY2875358 may provide a promising therapeutic strategy for patients whose tumors are driven by both HGF-dependent and HGF-independent MET activation. LY2875358 is currently being investigated in multiple clinical studies.
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Transgenic Expression of Human Cytoxic T-lymphocyte Associated Antigen4-Immunoglobulin (hCTLA4Ig) by Porcine Skin for Xenogeneic Skin Grafting
Transgenic Research.
Sep, 2014 |
Pubmed ID: 25236862 Porcine skin is frequently used as a substitute of human skin to cover large wounds in clinic practice of wound care. In our previous work, we found that transgenic expression of human cytoxicT-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) in murine skin graft remarkably prolonged its survival in xenogeneic wounds without extensive immunosuppression in recipients, suggesting that transgenic hCTLA4Ig expression in skin graft may be an effective and safe method to prolong xenogeneic skin graft survival. In this work, using a transgene construct containing hCTLA4Ig coding sequence under the drive of human Keratine 14 (k14) promoter, hCTLA4Ig transgenic pigs were generated by somatic nuclear transfer. The derived transgenic pigs were healthy and exhibited no signs of susceptibility to infection. The hCTLA4Ig transgene was stably transmitted through germline over generations, and thereby a transgenic pig colony was established. In the derived transgenic pigs, hCTLA4Ig expression in skin was shown to be genetically stable over generations, and detected in heart, kidney and corneal as well as in skin. Transgenic hCTLA4Ig protein in pigs exhibited expected biological activity as it suppressed human lymphocyte proliferation in human mixed lymphocyte culture to extents comparable to those of commercially purchased purified hCTLA4Ig protein. In skin grafting from pigs to rats, transgenic porcine skin grafts exhibited remarkably prolonged survival compared to the wild-type skin grafts derived from the same pig strain (13.33 ± 3.64 vs. 6.25 ± 2.49 days, P
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Improved Solubility and Stability of 7-hydroxy-4-methylcoumarin at Different Temperatures and PH Values Through Complexation with Sulfobutyl Ether-β-cyclodextrin
Food Chemistry.
Feb, 2015 |
Pubmed ID: 25172710 The inclusion complex of 7-hydroxy-4-methylcoumarin (7H4MC) with sulfobutyl ether-β-cyclodextrin (SBE-β-CD) was investigated by means of UV-vis, circular dichroism and (1)H NMR spectroscopy in phosphate buffer solutions at different temperatures and pH values. The stoichiometric ratio of the complexation was found to be 1:1 and the stability constants (KC) were estimated from phase solubility analysis. The thermodynamic parameters of standard Gibbs free energy change, ΔG(o), enthalpy change, ΔH(o), and entropy change, ΔS(o), for the complexation process were obtained by using the van't Hoff equation and Gibbs-Helmholtz equation. The large negative ΔH(o) and the small negative or positive ΔS(o) (|ΔH(o)|>|TΔS(o)|) demonstrated that the inclusion interaction was an enthalpy-driven process. The positive signal of circular dichroism indicated that 7H4MC penetrated the cavity in such a way that the transition moment of the guest chromophore was parallel to the long axis of SBE-β-CD cavity. Moreover, the (1)H NMR spectrum showed that the entire 7H4MC molecule, except the hydroxyl group, was included in the SBE-β-CD cavity.
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