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The challenge to improve the response of biomaterials to the physiological environment

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Regenerative Biomaterials 2016年第2期3卷 67-71页

作者： nicholas A.Peppas john R.Clegg McKetta Department of Chemical Engineering College of PharmacyUniversity of Texas at Austin Department of Biomedical Engineering College of PharmacyUniversity of Texas at Austin Institute for Biomaterials Drug Delivery and Regenerative MedicineCollege of PharmacyUniversity of Texas at Austin Department of Surgery and Perioperative Care Dell Medical SchoolCollege of PharmacyUniversity of Texas at Austin Division of Pharmaceutics College of PharmacyUniversity of Texas at Austin.

New applications of biomaterials often require advanced structures containing synthetic and natural components that are tuned to provide properties unique to a specific *** discuss how structural characteristics of biomaterials,especially hydrophilic ones,can be used in conjunction with non-ideal thermodynamics to develop advanced medical *** show a number of examples of biocompatible,intelligent biomaterials that can be used for organ replacement,biosensors,precise drug delivery over days or weeks,and regenerative medicine.

关键词： drug delivery nanobiomaterials regenerative mechanism materials structure

Assessment of strain bursting in deep tunnelling by using the finite-discrete element method

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journal of Rock Mechanics and Geotechnical Engineering 2019年第1期11卷 12-37页

作者： Ioannis Vazaios Mark S.Diederichs nicholas Vlachopoulos Department of Ceological Saences and Ceological Engineering Queen's UniversityKingstonCanada

Rockbursting in deep tunnelling is a complex phenomenon posing significant challenges both at the design and construction stages of an underground excavation within hard rock masses and under high in situ stresses. While local experience, field monitoring, and informed data-rich analysis are some of the tools commonly used to manage the hazards and the associated risks, advanced numerical techniques based on discontinuum modelling have also shown potential in assisting in the assessment of rockbursting. In this study, the hybrid finite-discrete element method(FDEM) is employed to investigate the failure and fracturing processes, and the mechanisms of energy storage and rapid release resulting in bursting, as well as to assess its utility as part of the design process of underground *** the calibration of the numerical model to simulate a deep excavation in a hard, massive rock mass, discrete fracture network(DFN) geometries are integrated into the model in order to examine the impact of rock structure on rockbursting under high in situ stresses. The obtained analysis results not only highlight the importance of explicitly simulating pre-existing joints within the model, as they affect the mobilised failure mechanisms and the intensity of strain bursting phenomena, but also show how the employed joint network geometry, the field stress conditions, and their interaction influence the extent and depth of the excavation induced damage. Furthermore, a rigorous analysis of the mass and velocity of the ejected rock blocks and comparison of the obtained data with well-established semi-empirical approaches demonstrate the potential of the method to provide realistic estimates of the kinetic energy released during bursting for determining the energy support demand.

关键词： Rockburst Finite-discrete element method(FDEM) Deep tunnelling Hard rock excavations Brittle fracturing Discrete fracture network(DFN)

Factor analysis identifies subgroups of constipation

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World journal of Gastroenterology 2011年第11期17卷 1468-1474页

作者： Philip G Dinning Mike jones Linda Hunt Sergio E Fuentealba jamshid Kalanter Denis W King David Z Lubowski nicholas j Talley Ian j Cook Department of Gastroenterology St.George HospitalUniversity of New South WalesKogarahNSW 2217Australia Department of Psychology Macquarie UniversityNSW 2109Australia Gastroenterology Research Unit Nepean HospitalUniversity of SydneySydneyNSW 2050Australia Department of Colorecta Surgery St.George HospitalKogarahNSW 2217Australia Gastroenterology and Hepatology Mayo ClinicJacksonvilleFL 32224United States

AIM:To determine whether distinct symptom groupings exist in a constipated population and whether such grouping might correlate with quantifiable pathophysiological measures of colonic ***:One hundred and ninety-one patients presenting to a Gastroenterology clinic with constipation and 32 constipated patients responding to a newspaper advertisement completed a 53-item,wide-ranging selfreport *** hundred of these patients had colonic transit measured *** analysis determined whether constipation-related symptoms grouped into distinct aspects of *** analysis was used to determine whether indi-vidual patients naturally group into distinct ***:Cluster analysis yielded a 4 cluster solution with the presence or absence of pain and laxative unresponsiveness providing the main *** all clusters there was a considerable proportion of patients with demonstrable delayed colon transit,irritable bowel syndrome positive criteria and regular stool *** majority of patients with these characteristics also reported regular laxative ***:Factor analysis identified four constipation subgroups,based on severity and laxative unresponsiveness,in a constipated ***,clear stratification into clinically identifiable groups remains imprecise.

关键词： Factor analysis Constipation Symptoms Clusters Laxatives

Loss of Hox5 function results in myofibroblast mislocalization and distal lung matrix defects during postnatal development

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Science China(Life Sciences) 2018年第9期61卷 1030-1038页

作者： Steven M.Hrycaj Leilani Marty-Santos ANDrew j.Rasky nicholas W.Lukacs Deneen M.Wellik Department of Internal Medicine Division of Molecular Medicine and Genetics University of Michigan Department of Pathology University of Michigan Department of Cell and Developmental Biology University of Michigan

Alveologenesis is the final stage of lung development and is responsible for the formation of the principle gas exchange units called alveoli. The lung mesenchyme, in particular the alveolar myofibroblasts, are drivers of alveolar development, however,few key regulators that govern the proper distribution and behavior of these cells in the distal lung during alveologenesis have been identified. While Hox5 triple mutants(Hox5 aabbcc) exhibit neonatal lethality, four-allele, compound mutant mice(Hox5 AabbCc) are born in Mendelian ratios and are phenotypically normal at birth. However, they exhibit defects in alveologenesis characterized by a BPD-like phenotype by early postnatal stages that becomes more pronounced at adult stages. Invasive pulmonary functional analyses demonstrate significant increases in total lung volume and compliance and a decrease in elastance in Hox5 compound mutants. SMA+ myofibroblasts in the distal lung are distributed abnormally during peak stages of alveologenesis and aggregate, resulting in the formation of a disrupted elastin network. Examination of other key components of the distal lung ECM, as well as other epithelial cells and lipofibroblasts reveal no differences in distribution. Collectively, these data indicate that Hox5 genes play a critical role in alveolar development by governing the proper cellular behavior of myofibroblasts during alveologenesis.

关键词： Hox5 alveologenesis alveolar myofibroblasts lung ECM postnatal lung development

New pharmacotherapies for diabetic retinopathy

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Annals of Eye Science 2018年第1期3卷 293-305页

作者： Doran B.Spencer nicholas j.Protopsaltis Daniel L.Chao Shiley Eye Institute Department of OphthalmologyUniversity of CaliforniaSan DiegoCAUSA

Diabetic retinopathy(DR)is the most common microvascular complication in patients with diabetes mellitus(DM),and remains the single greatest cause of blindness in working age adults around the *** this article,we review the evolution of pharmacotherapies for both diabetic macular edema(DME)and DR such as anti-vascular endothelial growth factor inhibitors and various steroid formulations,as well as other emerging pharmacotherapies currently in late stage clinical testing for this disease.

关键词： Diabetic retinopathy(DR) diabetic macular edema(DME) vascular endothelial growth factor steroids clinical trials

Integration of solid phase extraction with HILIC-MS/MS for analysis of free amino acids in source water

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journal of Environmental Sciences 2022年第7期34卷 190-196页

作者： junlang Qiu Caley Craven nicholas Wawryk Kristin Carroll Xing-Fang Li Division of Analytical and Environmental Toxicology Department of Laboratory Medicine and PathologyUniversity of AlbertaEdmontonT6G 2G3Canada School of Environmental Science and Engineering Sun Yat-sen UniversityGuangzhou 510006China

Amino acids(AAs) are prevalent in source water, particularly during spring run-off. Monitoring of amino acids in source water is desirable for water treatment plants(WTP) to indicate changes in source water quality. The objective of this study was to establish analytical procedures for reliable monitoring of amino acids in source water. Therefore, we examined two different methods, large volume inject(LVI) and solid phase extraction(SPE), for sample preparation prior to HILIC-MS/MS. The LVI-HILIC-MS/MS method can provide fast and sensitive detection for clean samples, but suffers from matrix effects, resulting in irreproducible separation and shortening column lifetime. We have demonstrated that SPE was necessary prior to HILIC-MS/MS to achieve reproducible and reliable quantification of AAs in source water. A natural heterocyclic amine 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid(MTCCA) was also included in the method to indicate changes in other natural nitrogenous compounds in source water. The SPE-HILIC-MS/MS method was able to achieve limits of detection from 2.6-3400 ng/L for the amino acids and MTCCA with RSDs( n = 3) of 1.1%-4.8%. As well, retention times(RT) of the analytes were reproducible with variation less than 0.01 min( n = 3) through the entire project. We further applied the SPE-HILICMS/MS method to determine AAs in authentic source water samples collected from two drinking water treatment plants(WTPs) during the 2021 spring run-off season. The results support that the SPE-HILIC-MS/MS method does not require derivatization and can provide reliable, accurate, and robust analysis of AAs and MTCCA in source water, supporting future monitoring of source water quality.

关键词： Water analysis Disinfection byproducts Amino acids HPLC MS HILIC

Neutralising effects of small molecule toxin inhibitors on nanofractionated coagulopathic Crotalinae snake venoms

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Acta Pharmaceutica Sinica B 2020年第10期10卷 1835-1845页

作者： Chunfang Xie julien Slagboom Laura-Oana Albulescu Govert W.Somsen Freek j.Vonk nicholas R.Casewell jeroen Kool Amsterdam Institute of Molecular and Life Sciences Division of BioAnalytical ChemistryDepartment of Chemistry and Pharmaceutical SciencesFaculty of ScienceVrije Universiteit AmsterdamAmsterdam 1081HVThe Netherlands Centre for Analytical Sciences Amsterdam(CASA) Amsterdam 1098 XHThe Netherlands Centre for Snakebite Research and Interventions Liverpool School of Tropical MedicineLiverpool L35QAUK Centre for Drugs and Diagnostics Liverpool School of Tropical MedicineLiverpool L35QAUK Naturalis Biodiversity Center Leiden 2333 CRThe Netherlands

Repurposing small molecule drugs and drug candidates is considered as a promising approach to revolutionise the treatment of snakebite *** this study,we investigated the inhibiting effects of the small molecules varespladib(nonspecific phospholipase A2 inhibitor),marimastat(broad spectrum matrix metalloprotease inhibitor)and dimercaprol(metal ion chelator)against coagulopathic toxins found in Crotalinae(pit vipers)snake *** from Bothrops asper,Bothrops jararaca,Calloselasma rhodostoma and Deinagkistrodon acutus were separated by liquid chromatography,followed by nanofractionation and mass spectrometry identification undertaken in *** of the venom toxins were then subjected to a high-throughput coagulation assay in the presence of different concentrations of the small molecules under *** venom toxins were mostly identified as phospholipases A2,while procoagulant venom activities were mainly associated with snake venom metalloproteinases and snake venom serine *** was found to effectively inhibit most anticoagulant venom effects,and also showed some inhibition against procoagulant ***,marimastat and dimercaprol were both effective inhibitors of procoagulant venom activities but showed little inhibitory capability against anticoagulant *** information obtained from this study aids our understanding of the mechanisms of action of toxin inhibitor drug candidates,and highlights their potential as future snakebite treatments.

关键词： Snakebite Antivenom Varespladib Marimastat Dimercaprol Chelators Nanofractionation

The efficacy of a verification stage for determining VO_(2max)and the impact of sampling intervals

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Sports Medicine and Health Science 2023年第2期5卷 101-105页

作者： Emily j.Kontos nicholas D.Luden Stephanie Kurti Christopher j.Womack Human Performance Laboratory Department of KinesiologyJames Madison UniversityHarrisonburgVA22801USA

It is unknown whether oxygen uptake(VO_(2))sampling intervals influence the efficacy of a verification stage following a graded exercise test(GXT).Fifteen females and 14 males(18-25 years)completed a maximal treadmill *** a 5min recovery,the verification stage began at the speed and grade corresponding with the penultimate stage from the *** oxygen consumption(VO_(2max))from the incremental GXT(iVO_(2max))and VO_(2max)from the verification stage(verVO_(2max))were determined using 10 seconds(s),30s,and 60s from breath×breath *** was no main effect for VO_(2max)measure(iVO_(2max)***_(2max))10s([47.9±8.31]ml∙kg^(−1)∙min^(−1)vs[48.85±7.97]ml∙kg^(−1)∙min^(−1)),30s([46.94±8.62]ml∙kg^(−1)∙min^(−1)vs[47.28±7.97]ml∙kg^(−1)∙min^(−1)),and 60s([46.17±8.62]ml∙kg^(−1)∙min^(−1)vs[46.00±8.00]ml∙kg^(−1)∙min^(−1)].There was a stage×sampling interval interaction as the difference between(verVO_(2max)−iVO_(2max))was greater for 10-s than 60-s sampling *** verVO_(2max)was>4%higher than iVO_(2max)in 31%,31%,and 17%of the tests for the 10-s,30-s,and 60-s sampling intervals *** for the plateau was90%for all sampling intervals;while specificity was<25%.Findings from the present study suggest that the efficacy of verification stages for eliciting a higher VO_(2max)may be influenced by the sampling interval utilized.

关键词： VO_(2max)testing Verification stage VO_(2max)criteria specificity VO_(2max)criteria sensitivity

Macrophage-targeted single walled carbon nanotubes stimulate phagocytosis via pH-dependent drug release

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Nano Research 2021年第3期14卷 762-769页

作者： Yapei Zhang jianqin Ye Niloufar Hosseini-Nassab Alyssa Flores Irina Kalashnikova Sesha Lakshmi Paluri Mozhgan Lotfi nicholas j.Leeper Bryan Ronain Smith Department of Biomedical Engineering Michigan State UniversityEast LansingMI48824USA Institute for Quantitative Health Science and Engineering Michigan State UniversityEast LansingMI48824USA Department of Surgery Division of Vascular SurgeryStanford University School of MedicineStanfordCA94305USA Department of Medicine Division of Cardiovascular MedicineStanford University School of MedicineStanfordCA94305USA Stanford Cardiovascular Institute StanfordCA94305USA Department of Radiology Stanford University School of MedicineStanfordCA94305USA

Atherosclerotic cardiovascular disease is the leading cause of mortality in the world.A driving feature of atherosclerotic plaque formation is dysfunctional *** the“don’t eat me”molecule CD47 is upregulated in atherosclerotic plaque cores,CD47-blocking strategies can stimulate the efferocytic clearance of apoptotic cells and thereby help prevent the progression of plaque ***,these therapies are generally costly and,in clinical and murine trials,they have resulted in side effects including anemia and ***,we developed and characterized an intracellular phagocytosis-stimulating treatment in the CD47-SIRPα*** loaded a novel monocyte/macrophage-selective nanoparticle carrier system with a small molecule enzymatic inhibitor that is released in a pH-dependent manner to stimulate macrophage efferocytosis of apoptotic cell debris via the CD47-SIRPαsignaling *** demonstrated that single-walled carbon nanotubes(SWNTs)can selectively deliver tyrosine phosphatase inhibitor 1(TPI)intracellularly to macrophages,which potently stimulates efferocytosis,and chemically characterized the ***,SWNT-delivered TPI can stimulate macrophage efferocytosis,with the potential to reduce or prevent atherosclerotic disease.

关键词： macrophages phagocytosis single-walled carbon nanotubes tyrosine phosphatase 1(SHP1)inhibitor atherosclerosis