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| 1 | Targeting DNA Double-Strand Breaks with TAL Effector Nucleases显示文摘 | Christian Michelle Cermak Tomas Doyle Erin L Schmidt Clarice Zhang Feng Hummel Aaron Bogdanove Adam J Voytas Daniel F | 2010 | Genetics2010，，2： | 3 |
| 2 | 群体药动学:理论与实践显示文摘目前由于对在新药发展计划中的早期阶段未在可能使用它的有关人群中进行该药的药动学研究的关切,从而引起了对群体药动学的兴趣。它研究在目标群体中给予同样的标准剂量方案时,个体间血浆药物浓度的差异,并探讨控制这种变异的因素,从而有助于该药使用时剂量方案的制订与调整。本文叙述了对群体药动学的理论意义与实施中的方法等具体问题。 | Aarons L 李元敏 | 1992 | 国外医学(药学分册)1992，19，5： | 3 |
| 3 | Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice显示文摘BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity.The protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2(SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic retinopathy.AIM To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse model.METHODS The SGLT2 inhibitors empagliflozin or dapagliflozin(25 mg/kg/d) or vehicle dimethylsulfoxide(DMSO) were administered to C57 BL/6 J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid(SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay(ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield microscopy.RESULTS Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57 BL/6 J and Kimba mice.Furthermore, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced in Akimba mice when compared to DMSO treated mice. In addition, empagliflozin resulted in suppression of succinate levels in Akimba mice. The beneficial SCFA known as butyric acid was significantly increased in Akita mice after treatment with dapagliflozin when compared to vehicle treated mice. The norepinephrine content in the kidney was significantly reduced with both dapagliflozin and empagliflozin therapy in Akita mice and was significantly reduced in Akimba mice treated with empagliflozin.In non-diabetic C57 BL/6 J and Kimba mice, serum leptin levels were significantly reduced after dapagliflozin therapy.CONCLUSION The inhibition of SGLT2 reduces the intermediate metabolite succinate, increases SCFA butyric acid levels and reduces norepinephrine content in mouse models of T1 D. Collectively, these improvements may represent an important mechanism underlying the potential benefits of SGLT2 inhibition in T1 D and its complications. | Lakshini Y Herat Natalie C Ward Aaron L Magno Elizabeth P Rakoczy Marcio G Kiuchi Markus P Schlaich Vance B Matthews | 2020 | World Journal of Gastroenterology2020，26，23： | 3 |
| 4 | Suppressing tawny crazy ant (Nylanderia fulva) by RNAi technology显示文摘A bstract The tawny crazy ant(Nylanderia fulva)is a new invasive pest in the United States.At present,its management mainly relies on the use of synthetic insecticides,which are generally ineffective at producing lasting control of the pest,necessitating alternative environmentally friendly measures.In this study,we evaluated the feasibility of gene silencing to control this ant species.Six housekeeping genes encoding actin(NfActin),coatomer subunit β (NfCOPP),arginine kinase(NfArgK),and V-type proton ATPase subunits A(NfvATPaseA),B(NfvATPaseB)and E(NfvATPaseE)were cloned.Phylogenetic analysis revealed high sequence similarity to homologs from other ant species,particularly the Florida carpenter ant(Camponotus floridanus).To silence these genes,vector L4440 was used to generate six specific RNAi constructs for bacterial expression.Heat-inactivated,dsRNA-expressing Escherichia coli were incorporated into artificial diet.Worker ants exhibited reduced endogenous gene expression after feeding on such diet for 9 d.However,only ingestion of dsRNAs of NfCOPfi(a gene involved in protein trafficking)and NfArgK(a cellular energy reserve regulatory gene in invertebrates)caused modest but significantly higher ant mortality than the control.These results suggest that bacterially expressed dsRNA can be orally delivered to ant cells as a mean to target its vulnerabilities.Improved efficacy is necessary for the RNAi-based approach to be useful in tawny crazy ant management. | Jia Meng Jiaxin Lei Andrew Davitt Jocelyn RHolt Jian Huang Roger Gold Edward L Vargo Aaron MTarone Keyan Zhu-Salzman | 2020 | Insect Science2020，27，1： | 2 |
| 5 | Self-efficacy Is Associated with Pain, Functioning, and Coping in Patients with Chronic Temporomandibular Disorder Pain显示文摘 | Brister H Turner J A Aaron L A | 2006 | J Orofac Pain2006，20，2： | 1 |
| 6 | Metabolism of theophylline and its inhibition by Fluoroquinolones in rat hepatic microsomes显示文摘 | Davis JD Aarons L Houston JB | 1995 | Xenobiotica1995，25，6： | 1 |
| 7 | Molecular phylogenetics of the clover genus ( Trifolium- Leguminosae ) 显示文摘 | ELLISON N W AARON L JEFFEREY J S | 2006 | Molecular Phylogenetics and Evolution2006，39，： | 1 |
| 8 | A physiologically based pharmacokinetic model for Valproic acid in adults and children显示文摘 | Ogungbenro K Aarons L | 2014 | Eur J Pharm Sci2014，63，10： | 1 |
| 9 | Interleukin-10 regulation in normal subjects and patients with asthma显示文摘 | Borish L Aarons A Rumbyrt J | 1966 | J Allergy Clin Immunol1966，97，： | 1 |
| 10 | Capillary electrophoresis of free fatty acids by indirect uhraviolet 显示文摘 | Maria V B Aaron E D Maria J L G | 2011 | Journal of Agriculture and Food Chemistry2011，59，10： | 1 |
| 11 | Interleukin-10 regulation in normal subjects and patients with asthma显示文摘 | Borish L Aarons A Rumbyrt J | 2003 | J Allergy Clin Immunol2003，97，6： | 1 |
| 12 | Hegemony with Chinese Characteristics显示文摘 | Friedberg Aaron L | 2011 | The National Interest2011，，114： | 1 |
| 13 | Diazepam pharamacokinetics from preclinical to phase Ⅰ using a bayesian population physiologically based pharmacokinetle model with informative prior distributions in winbugs 显示文摘 | Gueorguieva I Aarons L Rowland M | 2006 | Journal of Pharmacokinetics and Pharmacodynamics2006，33，5： | 1 |
| 14 | Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction 显示文摘 | JAMES L JANUZZI JR MD SHAFIQ U REHMAN M D ASIM A MOHAMMED M D ANJU BHARDWAJ M D LINDA BARAJAS R N JUSTINE BARAJAS HAN-NA KIM M D MPH AARON L BAGGISH M D RORY B WEINER M D ANNABEL CHEN-TOURNOUX MD JANE E MARSHALL RDCS STEPHANIE A MOORE M D WILLIAM D CARLSON M D GREGORY D LEWIS M D JORDAN SHIN M D DOROTHY SULLIVAN ANP KIMBERLY PARKS D O THOMAS J WANG M D SHAWN A GREGORY M D SHANMUGAM UTHAMALINGAM M D MARC J SEMIGRAN M D | 2011 | J Am Coll Cardiol2011，58，18： | 1 |
| 15 | Inhibition of constitutive aryl hydrocarbon receptor ( AhR ) signaling attenuates androgen independent signaling and growth in ( C4-2 ) prostate cancer cells显示文摘 | Tran C Richmond O Aaron L | 2013 | Biochemical Pharmacology2013，85，6： | 1 |
| 16 | A rapid method for the simultaneous determination of the major metabolites of sulphasalazine in plasma显示文摘 | Shaw PN Sivner AL Aarons L | 1983 | J Chromatogr1983，274，： | 1 |
| 17 | Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease显示文摘 | Aaron S D Vandemheen K L Hebert P | 2003 | N Engl J Med2003，348，： | 1 |
| 18 | Simultaneous assay of fluoroquinolones and theophyline in plasma by high-performancc liquid chromatography显示文摘 | Davis J D Aarons L Houston J B | 1993 | J Chromatogr1993，621，1： | 1 |
| 19 | Blood pressure, atherosclerosis, and albuminuria in 10 113 participants in the Atherosclerosis Risk In Communities study显示文摘 | Charles C Hsu Frederick L Brancati Brad C Astor Wen Hong Kao Michael W Steffes Aaron R Folsom Josef Coresh | 2009 | Journal of Hypertension2009，，2： | 1 |
| 20 | Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease 显示文摘 | Aaron S D Vandemheen K L Hebert P | 2003 | N Engl J Med2003，348，26： | 1 |
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